WO2023131872A2

WO2023131872A2 - Rectal administration techniques

Info

Publication number: WO2023131872A2
Application number: PCT/IB2023/050001
Authority: WO
Inventors: Noa BARTOV
Original assignee: Bartov Noa
Priority date: 2022-01-04
Filing date: 2023-01-01
Publication date: 2023-07-13
Also published as: WO2023131872A3

Abstract

A wipe (40B), formulated for rectal administration, and comprising a respiratory virus, such as an influenza virus or a coronavirus. Other embodiments are also described.

Description

RECTAL ADMINISTRATION TECHNIQUES

CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] The present application claims priority from Provisional US Patent Application 63/296,231 to Bartov, filed January 4, 2022, and titled "Rectal administration techniques," which is incorporated herein by reference.

FIELD OF THE INVENTION

[0002] Some applications of the present invention relate in general to rectal administration of substances. More specifically, some applications of the present invention relate to rectal inoculation of pathogens.

BACKGROUND

[0003] Global travel causing rapid contact among populations worldwide has facilitated the ability of rapidly mutating viral pathogens to add a huge burden of disease to the world. This is especially applicable to communicable diseases spread by inhalation or contact. Means of preventing, mitigating the transfer and severity of disease, and even treating infectious diseases without simultaneously causing significant morbidity is therefore an urgent priority.

SUMMARY OF THE INVENTION

[0004] This summary is meant to provide some examples and is not intended to be limiting of the scope of the invention in any way. For example, any feature included in an example of this summary is not required by the claims, unless the claims explicitly recite the features. Also, the features, components, steps, concepts, etc. described in examples in this summary and elsewhere in this disclosure can be combined in a variety of ways. Various features and steps as described elsewhere in this disclosure may be included in the examples summarized here.

[0005] In some applications, a method includes identifying a human subject to be inoculated with (e.g., immunized against) a non-gastrointestinal pathogen, e.g., a respiratory virus or a central nervous system (CNS) virus, and then rectally inoculating (e.g., infecting) the subject with the pathogen. This inoculation may stimulate a mucosal and/or systemic immune response to the pathogen, without causing substantial morbidity to the subject. [0006] In some applications, the formulation may comprise a live virus. For some such applications, the live virus may be unencapsulated (e.g. may have been unencapsulated for use in the formulation). For some applications, the virus may be a live attenuated form of the virus. For some applications, the virus may be an inactive form of the virus (e.g., heat- inactivated or chemically-inactivated).

[0007] In some applications, the virus may be a recombinant virus (e.g. influenza virus) that encodes (e.g. has been engineered to encode) an epitope that stimulates an immune response to another pathogen. For example, the virus may encode an epitope of the other pathogen.

[0008] In some applications, rather than virus particles, the formulation may comprise viral antigens and/or nucleic acid encoding specific viral antigens.

[0009] In some applications, the pathogen may be a non-viral, e.g., bacterial or fungal, pathogen.

[0010] For some applications, such rectal administration or application may be achieved using an enema, a suppository, a swab, or a wipe.

[0011] In some applications, a suppository is provided comprising an active ingredient (such as a formulation described hereinbelow) and a reporter dye. For some such applications, the reporter dye is included as a discrete part of a capsule surrounding the active ingredient, e.g., a pathogen. Alternatively or additionally, the reporter dye may be included as a mixture with the active ingredient.

[0012] There is therefore provided, in accordance with some applications of the present invention, a method, including: identifying a human subject to be inoculated with a coronavirus, and responsively to the identifying, inoculating the subject with the coronavirus by rectally administering, to the subject, a formulation including the coronavirus.

[0013] For some applications, the formulation includes a suspension of cells supportive of the coronavirus, and rectally administering the formulation includes rectally administering the formulation that includes the suspension of cells supportive of the coronavirus.

[0014] For some applications, inoculating the subject with the coronavirus by rectally administering the coronavirus includes rectally administering a formulation including coronavirus SARS-CoV-2. [0015] For some applications, rectally administering the formulation including the coronavirus includes rectally administering lxlO^A2 to lxl0^A10, for example, lxlO^A4, plaque forming units of the virus to the subject.

[0016] For some applications, the virus being taken up by at least one cell in the gastrointestinal tract induces a systemic immune response to the coronavirus in the subject.

[0017] For some applications, rectally administering the formulation includes rectally administering the formulation in an enema formulation.

[0018] For some applications, rectally administering the formulation includes rectally administering the formulation using a swab applicator.

[0019] For some applications, rectally administering the formulation includes rectally administering the formulation using a wet- wipe- style device.

[0020] For some applications, rectally administering the formulation includes rectally administering the formulation in a suppository.

[0021] For some applications, rectally administering the formulation in a suppository includes rectally administering the formulation in a suppository including a reporter dye.

[0022] For some applications, the method further includes checking for a presence of the reporter dye.

[0023] For some applications, rectally administering the formulation includes rectally administering a first dose of the formulation, and the method further includes rectally administering a second dose of the formulation.

[0024] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 12-18 months after rectally administering the first dose of the formulation.

[0025] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 3-24 months after rectally administering the first dose of the formulation.

[0026] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 6-24 months after rectally administering the first dose of the formulation. [0027] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 12-24 months after rectally administering the first dose of the formulation.

[0028] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 6-18 months after rectally administering the first dose of the formulation.

[0029] There is further provided, in accordance with some applications of the present invention, a method, including: identifying a human subject to be inoculated with a central nervous system (CNS) virus, and responsively to the identifying, inoculating the subject with the CNS virus by rectally administering, to the subject, a formulation including the CNS virus.

[0030] For some applications, the formulation includes a suspension of cells supportive of the CNS virus, and rectally administering the formulation includes rectally administering the formulation that includes the suspension of cells supportive of the CNS virus.

[0031] For some applications, inoculating the subject with the CNS virus by rectally administering the CNS virus includes rectally administering a formulation including at least one CNS virus selected from the group consisting of: an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), and a varicella zoster virus (VZV).

[0032] For some applications, rectally administering the formulation including the CNS virus includes rectally administering lxlO^A2 to lxl0^A10, for example, lxlO^A4, plaque forming units of the virus to the subject.

[0033] For some applications, the virus being taken up by at least one cell in the gastrointestinal tract induces a systemic immune response to the CNS virus in the subject.

[0034] For some applications, rectally administering the formulation includes rectally administering the formulation in an enema formulation.

[0035] For some applications, rectally administering the formulation includes rectally administering the formulation using a swab applicator.

[0036] For some applications, rectally administering the formulation includes rectally administering the formulation using a wet- wipe- style device. [0037] For some applications, rectally administering the formulation includes rectally administering the formulation in a suppository.

[0038] For some applications, rectally administering the formulation in a suppository includes rectally administering the formulation in a suppository including a reporter dye.

[0039] For some applications, the method further includes checking for a presence of the reporter dye.

[0040] For some applications, rectally administering the formulation includes rectally administering a first dose of the formulation, and the method further includes rectally administering a second dose of the formulation.

[0041] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 12-18 months after rectally administering the first dose of the formulation.

[0042] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 3-24 months after rectally administering the first dose of the formulation.

[0043] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 6-24 months after rectally administering the first dose of the formulation.

[0044] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 12-24 months after rectally administering the first dose of the formulation.

[0045] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 6-18 months after rectally administering the first dose of the formulation.

[0046] There is further provided, in accordance with some applications of the present invention, a method, including: identifying a human subject to be inoculated with a respiratory virus, and responsively to the identifying, inoculating the subject with the respiratory virus by rectally administering, to the subject, a formulation including the respiratory virus.

[0047] For some applications, the formulation includes a suspension of cells supportive of the respiratory virus, and rectally administering the formulation includes rectally administering the formulation that includes the suspension of cells supportive of the respiratory virus.

[0048] For some applications, inoculating the subject with the respiratory virus by rectally administering the respiratory virus includes rectally administering a formulation including at least one respiratory virus selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus.

[0049] For some applications, rectally administering the formulation including the respiratory virus includes rectally administering lxlO^A2 to lxl0^A10, for example, lxlO^A4, plaque forming units of the virus to the subject.

[0050] For some applications, the respiratory virus being taken up by at least one cell in the gastrointestinal tract induces a systemic immune response to the respiratory virus in the subject.

[0051] For some applications, rectally administering the formulation includes rectally administering the formulation in an enema formulation.

[0052] For some applications, rectally administering the formulation includes rectally administering the formulation using a swab applicator.

[0053] For some applications, rectally administering the formulation includes rectally administering the formulation using a wet- wipe- style device.

[0054] For some applications, rectally administering the formulation includes rectally administering the formulation in a suppository.

[0055] For some applications, rectally administering the formulation in a suppository includes rectally administering the formulation in a suppository including a reporter dye.

[0056] For some applications, the method further includes checking for a presence of the reporter dye.

[0057] For some applications, rectally administering the formulation includes rectally administering a first dose of the formulation, and the method further includes rectally administering a second dose of the formulation. [0058] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 12-18 months after rectally administering the first dose of the formulation.

[0059] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 3-24 months after rectally administering the first dose of the formulation.

[0060] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 6-24 months after rectally administering the first dose of the formulation.

[0061] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 12-24 months after rectally administering the first dose of the formulation.

[0062] For some applications, rectally administering the second dose of the formulation includes rectally administering the second dose of the formulation 6-18 months after rectally administering the first dose of the formulation.

[0063] There is further provided, in accordance with some applications of the present invention, an enema formulation including a coronavirus.

[0064] For some applications, the enema formulation further includes a suspension of cells supportive of the coronavirus.

[0065] For some applications, the enema formulation includes an emulsion.

[0066] For some applications, the enema formulation includes a solution.

[0067] For some applications, the enema formulation includes a suspension.

[0068] For some applications, the enema formulation includes a liquid.

[0069] For some applications, the coronavirus is unencapsulated.

[0070] For some applications, the coronavirus is SARS-CoV-2.

[0071] For some applications, the coronavirus is live.

[0072] For some applications, the coronavirus is heat inactivated.

[0073] For some applications, the coronavirus is heat-sensitive.

[0074] For some applications, the coronavirus is chemically inactivated. [0075] For some applications, the enema formulation is maintained in a frozen state until administration.

[0076] For some applications, the coronavirus is attenuated.

[0077] For some applications, the enema formulation further includes lyophilization stabilizers.

[0078] For some applications, the enema formulation further includes penetrants.

[0079] For some applications, the enema formulation includes the coronavirus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0080] For some applications, the enema formulation includes the coronavirus at approximately lxlO^A4 PFU per dose.

[0081] There is further provided, in accordance with some applications of the present invention, an enema formulation including an Epstein-Barr virus (EBV).

[0082] There is further provided, in accordance with some applications of the present invention, an enema formulation including a cytomegalovirus (CMV).

[0083] There is further provided, in accordance with some applications of the present invention, an enema formulation including Helicobacter pylori.

[0084] There is further provided, in accordance with some applications of the present invention, a suppository, formulated for rectal administration, and including a coronavirus.

[0085] For some applications, the suppository further includes a suspension of cells supportive of the coronavirus.

[0086] For some applications, the suppository further includes a layered capsule.

[0087] For some applications, the coronavirus is unencapsulated.

[0088] For some applications, the coronavirus is SARS-CoV-2.

[0089] For some applications, the coronavirus is live.

[0090] For some applications, the coronavirus is heat inactivated.

[0091] For some applications, the coronavirus is heat-sensitive.

[0092] For some applications, the coronavirus is chemically inactivated. [0093] For some applications, the suppository is maintained in a frozen state until administration.

[0094] For some applications, the coronavirus is attenuated.

[0095] For some applications, the suppository further includes lyophilization stabilizers.

[0096] For some applications, the suppository further includes penetrants.

[0097] For some applications, the suppository includes the coronavirus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0098] For some applications, the suppository includes the coronavirus at approximately lxlO^A4 PFU per dose.

[0099] There is further provided, in accordance with some applications of the present invention, a suppository, formulated for rectal administration, and including an Epstein-Barr virus (EBV).

[0100] There is further provided, in accordance with some applications of the present invention, a suppository, formulated for rectal administration, and including a cytomegalovirus (CMV).

[0101] There is further provided, in accordance with some applications of the present invention, a suppository, formulated for rectal administration, and including Helicobacter pylori.

[0102] There is further provided, in accordance with some applications of the present invention, a swab-compatible gel, formulated for rectal administration, and including a coronavirus.

[0103] For some applications, the swab-compatible gel further includes a suspension of cells supportive of the coronavirus.

[0104] For some applications, the swab-compatible gel includes a polymer.

[0105] For some applications, the coronavirus is unencapsulated.

[0106] For some applications, the coronavirus is SARS-CoV-2.

[0107] For some applications, the coronavirus is live.

[0108] For some applications, the coronavirus is heat inactivated.

[0109] For some applications, the coronavirus is heat-sensitive. [0110] For some applications, the coronavirus is chemically inactivated.

[0111] For some applications, the swab-compatible gel is maintained in a frozen state until administration.

[0112] For some applications, the coronavirus is attenuated.

[0113] For some applications, the swab-compatible gel further includes lyophilization stabilizers.

[0114] For some applications, the swab-compatible gel further includes penetrants.

[0115] For some applications, the swab-compatible gel includes the coronavirus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0116] For some applications, the swab-compatible gel includes the coronavirus at approximately lxlO^A4 PFU per dose.

[0117] There is further provided, in accordance with some applications of the present invention, a swab-compatible gel, formulated for rectal administration, and including an Epstein-Barr virus (EBV).

[0118] There is further provided, in accordance with some applications of the present invention, a swab-compatible gel, formulated for rectal administration, and including a cytomegalovirus (CMV).

[0119] There is further provided, in accordance with some applications of the present invention, a swab-compatible gel, formulated for rectal administration, and including Helicobacter pylori.

[0120] There is further provided, in accordance with some applications of the present invention, a wipe, formulated for rectal administration, and including a coronavirus.

[0121] For some applications, the wipe further includes a suspension of cells supportive of the coronavirus.

[0122] For some applications, the wipe includes a swab-compatible gel.

[0123] For some applications, the wipe includes a polymeric material.

[0124] For some applications, the coronavirus is unencapsulated.

[0125] For some applications, the coronavirus is SARS-CoV-2.

[0126] For some applications, the coronavirus is live. [0127] For some applications, the coronavirus is heat inactivated.

[0128] For some applications, the coronavirus is heat-sensitive.

[0129] For some applications, the coronavirus is chemically inactivated.

[0130] For some applications, the wipe is maintained in a frozen state until administration.

[0131] For some applications, the coronavirus is attenuated.

[0132] For some applications, the wipe further includes lyophilization stabilizers.

[0133] For some applications, the wipe further includes penetrants.

[0134] For some applications, the wipe includes the coronavirus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0135] For some applications, the wipe includes the coronavirus at approximately lxlO^A4 PFU per dose.

[0136] There is further provided, in accordance with some applications of the present invention, a wipe, formulated for rectal administration, and including an Epstein-Barr virus (EBV).

[0137] There is further provided, in accordance with some applications of the present invention, a wipe, formulated for rectal administration, and including a cytomegalovirus (CMV).

[0138] There is further provided, in accordance with some applications of the present invention, a wipe, formulated for rectal administration, and including Helicobacter pylori.

[0139] There is further provided, in accordance with some applications of the present invention, a suppository, formulated for rectal administration, and including a respiratory virus.

[0140] For some applications, the suppository includes a suspension of cells supportive of the respiratory virus.

[0141] For some applications, the respiratory virus is selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus.

[0142] For some applications, the suppository includes a layered capsule.

[0143] For some applications, the respiratory virus is unencapsulated. [0144] For some applications, the respiratory virus is SARS-CoV-2.

[0145] For some applications, the respiratory virus is live.

[0146] For some applications, the respiratory virus is heat inactivated.

[0147] For some applications, the respiratory virus is heat-sensitive.

[0148] For some applications, the respiratory virus is chemically inactivated.

[0149] For some applications, the suppository is maintained in a frozen state until administration.

[0150] For some applications, the respiratory virus is attenuated.

[0151] For some applications, the suppository further includes lyophilization stabilizers.

[0152] For some applications, the suppository further includes penetrants.

[0153] For some applications, the suppository further includes a high molecular weight glycoprotein.

[0154] For some applications, the suppository includes the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0155] For some applications, the suppository includes the respiratory virus at approximately lxlO^A4 PFU per dose.

[0156] There is further provided, in accordance with some applications of the present invention, a swab-compatible gel, formulated for rectal administration, and including a respiratory virus.

[0157] For some applications, the swab-compatible gel includes a suspension of cells supportive of the respiratory virus.

[0158] For some applications, the respiratory virus is selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus.

[0159] For some applications, the swab-compatible gel includes a polymer.

[0160] For some applications, the respiratory virus is unencapsulated.

[0161] For some applications, the respiratory virus is live.

[0162] For some applications, the respiratory virus is heat inactivated. [0163] For some applications, the respiratory virus is heat-sensitive.

[0164] For some applications, the respiratory virus is chemically inactivated.

[0165] For some applications, the swab-compatible gel is maintained in a frozen state until administration.

[0166] For some applications, the respiratory virus is attenuated.

[0167] For some applications, the swab-compatible gel further includes lyophilization stabilizers.

[0168] For some applications, the swab-compatible gel further includes penetrants.

[0169] For some applications, the swab-compatible gel further includes a high molecular weight glycoprotein.

[0170] For some applications, the swab-compatible gel includes the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0171] For some applications, the swab-compatible gel includes the respiratory virus at approximately lxlO^A4 PFU per dose.

[0172] There is further provided, in accordance with some applications of the present invention, an enema formulation including a respiratory virus.

[0173] For some applications, the enema formulation further includes a suspension of cells supportive of the respiratory virus.

[0174] For some applications, the respiratory virus is selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus.

[0175] For some applications, the enema formulation includes an emulsion.

[0176] For some applications, the enema formulation includes a solution.

[0177] For some applications, the enema formulation includes a suspension.

[0178] For some applications, the enema formulation includes a liquid.

[0179] For some applications, the respiratory virus is unencapsulated.

[0180] For some applications, the respiratory virus is live.

[0181] For some applications, the respiratory virus is heat inactivated. [0182] For some applications, the respiratory virus is heat-sensitive.

[0183] For some applications, the respiratory virus is chemically inactivated.

[0184] For some applications, the enema formulation is maintained in a frozen state until administration.

[0185] For some applications, the respiratory virus is attenuated.

[0186] For some applications, the enema formulation further includes lyophilization stabilizers.

[0187] For some applications, the enema formulation further includes penetrants.

[0188] For some applications, the enema formulation further includes a high molecular weight glycoprotein.

[0189] For some applications, the enema formulation includes the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0190] For some applications, the enema formulation includes the respiratory virus at approximately lxlO^A4 PFU per dose.

[0191] There is further provided, in accordance with some applications of the present invention, an enema formulation including a central nervous system (CNS) virus.

[0192] For some applications, the enema formulation includes a suspension of cells supportive of the CNS virus.

[0193] For some applications, the enema formulation includes an emulsion.

[0194] For some applications, the enema formulation includes a solution.

[0195] For some applications, the enema formulation includes a suspension.

[0196] For some applications, the enema formulation includes a liquid.

[0197] For some applications, the CNS virus is unencapsulated.

[0198] For some applications, the CNS virus includes at least one CNS virus selected from the group consisting of: an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), and a varicella zoster virus (VZV).

[0199] For some applications, the CNS virus is a first CNS virus, and the enema formulation further includes a second CNS virus. [0200] For some applications, the CNS virus is live.

[0201] For some applications, the CNS virus is heat inactivated.

[0202] For some applications, the CNS virus is heat-sensitive.

[0203] For some applications, the CNS virus is chemically inactivated.

[0204] For some applications, the enema formulation is maintained in a frozen state until administration.

[0205] For some applications, the CNS virus is attenuated.

[0206] For some applications, the enema formulation further includes lyophilization stabilizers.

[0207] For some applications, the enema formulation further includes penetrants.

[0208] For some applications, the enema formulation further includes a high molecular weight glycoprotein.

[0209] For some applications, the enema formulation includes the CNS virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0210] For some applications, the enema formulation includes the CNS virus at approximately lxlO^A4 PFU per dose.

[0211] There is further provided, in accordance with some applications of the present invention, a suppository, formulated for rectal administration, and including a central nervous system (CNS) virus.

[0212] For some applications, the suppository includes a suspension of cells supportive of the CNS virus.

[0213] For some applications, the suppository includes a layered capsule.

[0214] For some applications, the CNS virus is unencapsulated.

[0215] For some applications, the CNS virus includes at least one CNS virus selected from the group consisting of: an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), and a varicella zoster virus (VZV).

[0216] For some applications, the CNS virus is live.

[0217] For some applications, the CNS virus is heat inactivated. [0218] For some applications, the CNS virus is heat-sensitive.

[0219] For some applications, the CNS virus is chemically inactivated.

[0220] For some applications, the suppository is maintained in a frozen state until administration.

[0221] For some applications, the CNS virus is attenuated.

[0222] For some applications, the suppository further includes lyophilization stabilizers.

[0223] For some applications, the suppository further includes penetrants.

[0224] For some applications, the suppository further includes a high molecular weight glycoprotein.

[0225] For some applications, the suppository includes the CNS virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0226] For some applications, the suppository includes the CNS virus at approximately lxlO^A4 PFU per dose.

[0227] There is further provided, in accordance with some applications of the present invention, a swab-compatible gel, formulated for rectal administration, and including a central nervous system (CNS) virus.

[0228] For some applications, the swab-compatible gel further includes a suspension of cells supportive of the CNS virus.

[0229] For some applications, the swab-compatible gel includes a polymer.

[0230] For some applications, the CNS virus is unencapsulated.

[0231] For some applications, the CNS virus includes at least one CNS virus selected from the group consisting of: an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), and a varicella zoster virus (VZV).

[0232] For some applications, the CNS virus is live.

[0233] For some applications, the CNS virus is heat inactivated.

[0234] For some applications, the CNS virus is heat-sensitive.

[0235] For some applications, the CNS virus is chemically inactivated. [0236] For some applications, the swab-compatible gel is maintained in a frozen state until administration.

[0237] For some applications, the CNS virus is attenuated.

[0238] For some applications, the swab-compatible gel further includes lyophilization stabilizers.

[0239] For some applications, the swab-compatible gel further includes penetrants.

[0240] For some applications, the swab-compatible gel further includes a high molecular weight glycoprotein.

[0241] For some applications, the swab-compatible gel includes the CNS virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0242] For some applications, the swab-compatible gel includes the CNS virus at approximately lxlO^A4 PFU per dose.

[0243] There is further provided, in accordance with some applications of the present invention, a suppository for rectal administration, including: a capsule containing: an active ingredient; and a reporter dye.

[0244] For some applications, the active ingredient is a vaccine.

[0245] For some applications, the active ingredient is a drug.

[0246] For some applications, the active ingredient is an antigen.

[0247] For some applications, the active ingredient is an inactive virus.

[0248] For some applications, the active ingredient is a live virus.

[0249] For some applications, the active ingredient is nucleic acid encoding a viral antigen.

[0250] For some applications, the active ingredient is a bacterial pathogen.

[0251] For some applications, the reporter dye is fluorescent.

[0252] For some applications, the reporter dye is methylene blue.

[0253] For some applications, the reporter dye is indigo carmine.

[0254] For some applications, the reporter dye is turmeric. [0255] For some applications, the reporter dye is beet extract.

[0256] For some applications, the capsule includes a polymer.

[0257] For some applications, the suppository further includes lyophilization stabilizers.

[0258] For some applications, the suppository further includes penetrants.

[0259] For some applications, the suppository further includes a high molecular weight glycoprotein.

[0260] For some applications, the suppository is formulated such that the reporter dye includes part of the capsule.

[0261] For some applications, the capsule is produced by additive manufacturing.

[0262] For some applications, the suppository is produced by additive manufacturing.

[0263] For some applications, the capsule is produced by serial layer manufacturing.

[0264] For some applications, the suppository is produced by serial layer manufacturing.

[0265] For some applications, the capsule includes a first layer and a second layer.

[0266] For some applications, the first layer is an outer layer, and the second layer is an inner layer.

[0267] For some applications, the outer layer includes a polymeric substance.

[0268] For some applications, the inner layer includes the reporter dye.

[0269] For some applications, the active ingredient is a live virus.

[0270] For some applications, the live virus is maintained outside the capsule until administration.

[0271] For some applications, the live virus is a heat- sensitive strain of SARS-CoV-2.

[0272] For some applications, the capsule further includes a suspension of cells supportive of the live virus.

[0273] For some applications, the suspension of cells includes a first viral host cell type and a second viral host cell type.

[0274] For some applications, the first viral host cell type supports a different rate of viral replication compared with the second viral host cell type. [0275] There is further provided, in accordance with some applications of the present invention, a method, including: rectally administering a suppository to a subject, the suppository including a reporter dye; and subsequently, checking for rectal presence of the reporter dye.

[0276] For some applications, checking for rectal presence of the reporter dye is performed by wiping the perianal area with a disposable product and viewing the reporter dye on the disposable product.

[0277] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a tissue.

[0278] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a wet wipe.

[0279] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a swab.

[0280] There is further provided, in accordance with some applications of the present invention, a method, including: identifying a subject that has been rectally administered with a suppository that includes a reporter dye; and subsequently, checking for rectal presence of the reporter dye.

[0281] For some applications, checking for rectal presence of the reporter dye is performed by wiping the perianal area with a disposable product and viewing the reporter dye on the disposable product.

[0282] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a tissue.

[0283] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a wet wipe.

[0284] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a swab.

[0285] There is further provided, in accordance with some applications of the present invention, a method, including: rectally receiving a suppository that includes a reporter dye; and subsequently, checking for rectal presence of the reporter dye.

[0286] For some applications, checking for rectal presence of the reporter dye is performed by wiping the perianal area with a disposable product and viewing the reporter dye on the disposable product.

[0287] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a tissue.

[0288] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a wet wipe.

[0289] For some applications, wiping the perianal area with a disposable product includes wiping the perianal area with a swab.

[0290] There is further provided, in accordance with some applications of the present invention, a method, including: providing an encapsulating material, a reporter dye, and an active ingredient; and forming a suppository that includes the encapsulating material, the reporter dye, and the active ingredient.

[0291] For some applications, forming the suppository includes forming the suppository by additive manufacturing.

[0292] For some applications, forming the suppository includes forming the suppository by serial layer manufacturing.

[0293] For some applications, the reporter dye includes methylene blue, and forming the suppository includes forming the suppository that includes methylene blue.

[0294] For some applications, the reporter dye includes carmine red, and forming the suppository includes forming the suppository that includes carmine red.

[0295] For some applications, the reporter dye includes a turmeric extract, and forming the suppository includes forming the suppository that includes the turmeric extract.

[0296] For some applications, the reporter dye includes a beet extract, and forming the suppository includes forming the suppository that includes the beet extract.

[0297] For some applications, the reporter dye is fluorescent, and forming the suppository includes forming the suppository that includes the fluorescent reporter dye. [0298] For some applications, the reporter dye is chemiluminescent, and forming the suppository includes forming the suppository that includes the chemiluminescent reporter dye.

[0299] For some applications, the reporter dye is encapsulated in microbeads, and forming the suppository includes forming the suppository that includes the reporter dye that is encapsulated in microbeads.

[0300] For some applications, the active ingredient includes a SARS-CoV-2 virus, and forming the suppository includes forming the suppository that includes the SARS-CoV-2 virus.

[0301] For some applications, the active ingredient includes a respiratory pathogen, and forming the suppository includes forming the suppository that includes the respiratory pathogen.

[0302] For some applications, the active ingredient includes a central nervous system (CNS) pathogen, and forming the suppository includes forming the suppository that includes the CNS pathogen.

[0303] For some applications, the active ingredient includes a drug, and forming the suppository includes forming the suppository that includes the drug.

[0304] For some applications, the active ingredient includes a biomolecule, and forming the suppository includes forming the suppository that includes the biomolecule.

[0305] For some applications, the active ingredient includes a vaccine, and forming the suppository includes forming the suppository that includes the vaccine.

[0306] For some applications, the encapsulating material has a melting point of 25-37 degrees C, and forming the suppository includes forming the suppository with the encapsulating material that has the melting point that is between 25 and 37 degrees C.

[0307] For some applications, the encapsulating material includes glycerinated glycerin, and forming the suppository includes forming the suppository that includes glycerinated glycerin.

[0308] For some applications, the encapsulating material includes cocoa butter, and forming the suppository includes forming the suppository that includes cocoa butter. [0309] For some applications, the encapsulating material includes a polyethylene glycol, and forming the suppository includes forming the suppository that includes the polyethylene glycol.

[0310] For some applications, the encapsulating material includes a hydrogel, and forming the suppository includes forming the suppository that includes the hydrogel.

[0311] For some applications, forming the suppository includes adding a non-irritating excipient that has a melting point that is between 25 and 37 degrees C.

[0312] For some applications, forming the suppository includes forming the suppository to include the capsule and the reporter dye in an outer layer, and the active ingredient in a core internal to the outer layer.

[0313] For some applications, forming the suppository includes forming the suppository to include the capsule in a capsule layer, and the active ingredient and the reporter dye in a core internal to the capsule layer.

[0314] For some applications, forming the suppository includes forming the suppository to include the capsule in a capsule layer, the reporter dye in a reporter dye layer that is discrete from the capsule layer, and the active ingredient in a core that is discrete from the reporter dye layer.

[0315] For some applications, forming the suppository includes forming the suppository such that the reporter dye layer is internal to the capsule layer, and the core is internal to the reporter dye layer.

[0316] There is further provided, in accordance with some applications of the present invention, a method, including: lining a suppository capsule with a reporter dye; and subsequently, filling the lined capsule with an active ingredient.

[0317] For some applications, lining the capsule with the reporter dye includes lining the capsule with the reporter dye by serial layer manufacturing.

[0318] For some applications, the reporter dye includes methylene blue, and lining the suppository capsule with the reporter dye includes lining the suppository capsule with methylene blue. [0319] For some applications, the reporter dye includes carmine red, and lining the suppository capsule with the reporter dye includes lining the suppository capsule with carmine red.

[0320] For some applications, the reporter dye includes a turmeric extract, and lining a suppository capsule with the reporter dye includes lining the suppository capsule with the turmeric extract.

[0321] For some applications, the reporter dye includes a beet extract, and lining a suppository capsule with the reporter dye includes lining the suppository capsule with the beet extract.

[0322] For some applications, the active ingredient includes a SARS-CoV-2 virus, and filling the lined capsule with the active ingredient includes filling the lined capsule with the SARS-CoV-2 virus.

[0323] For some applications, the active ingredient includes a respiratory pathogen, and filling the lined capsule with the active ingredient includes filling the lined capsule with the respiratory pathogen.

[0324] For some applications, the active ingredient includes a central nervous system (CNS) pathogen, and filling the lined capsule with the active ingredient includes filling the lined capsule with the CNS pathogen.

[0325] For some applications, the active ingredient includes a drug, and filling the lined capsule with the active ingredient includes filling the lined capsule with the drug.

[0326] For some applications, the active ingredient includes a biomolecule, and filling the lined capsule with the active ingredient includes filling the lined capsule with the biomolecule.

[0327] For some applications, the active ingredient includes a vaccine, and filling the lined capsule with the active ingredient includes filling the lined capsule with the vaccine.

[0328] There is further provided, in accordance with some applications of the present invention, a method, including: forming an encapsulation mixture by mixing a reporter dye with a molten encapsulating material; and forming a suppository by encapsulating an active ingredient in the encapsulation mixture. [0329] There is further provided, in accordance with some applications of the present invention, a method, including: providing a dissolvable capsule; encapsulating an active ingredient as a solid insert in the capsule to create a suppository; and injecting a reporter dye between the capsule and the solid insert.

[0330] There is further provided, in accordance with some applications of the present invention, a method, including: identifying a human subject to be immunized against a non-gastrointestinal pathogen, and responsively to the identifying, rectally infecting the subject with the pathogen.

[0331] For some applications, the human subject is a human subject infected with the non- gastrointestinal pathogen, and the rectal infection is used as a means of stimulating a systemic immune response to the pathogen.

[0332] For some applications, the human subject is a human subject infected with the non- gastrointestinal pathogen, and the rectal infection is used as a means of stimulating an immune response to the pathogen.

[0333] The present invention will be more fully understood from the following detailed description of applications thereof, taken together with the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

[0334] Fig. 1 shows an exemplary application of the disclosed methods;

[0335] Figs. 2A-B, 3A-B, and 4-6 show exemplary means of applying an active formulation of the pathogen; and

[0336] Fig. 7 shows an alternative exemplary application of the disclosed methods.

DETAILED DESCRIPTION OF EMBODIMENTS

[0337] Herewithin are described methods for administering a non-gastrointestinal pathogen by rectally administering, via the anus of a subject, a formulation comprising the pathogen. For some applications, the pathogen is a virus. The pathogen may attach to cells in the gastrointestinal tract (e.g., may bind to specific receptors), may infect such cells, and/or may be taken up by such cells. The pathogen and/or fragments or components thereof may stimulate an immune response to the administered pathogen. For some applications, the immune response may be a systemic immune response. For some applications, the immune response may be a mucosal immune response. It is hypothesized that stimulating an immune response in this manner may provide immunization against the pathogen while avoiding at least some of the morbidity and/or danger associated with natural pathological infection and/or infection via the route by which the pathogen causes morbidity. For example, a respiratory pathogen administered rectally is hypothesized to avoid the morbidity associated with infection of the respiratory system.

[0338] Reference is now made to Fig. 1, which is a flowchart showing at least some steps of such a method 10, in accordance with some applications. Typically, a first step 12 is identifying a subject to be inoculated with (e.g. immunized against) the pathogen. Subsequently, the pathogen is rectally administered via the anus (step 14). For example, the pathogen may be administered as an enema, a suppository, or by a swab applicator.

[0339] For some applications, in a subsequent step 16, testing (e.g., serological testing) may be performed to detect a presence of antibodies to the pathogen in the blood or other fluid of the subject. Such testing may be performed a specific time interval, or multiple intervals, after step 14.

[0340] For some applications, the formulation may be administered exactly once. For some applications, the formulation may be administered more than once - e.g. at predefined time intervals. For example, in some applications, administration of the formulation may be administered 2, 3, or 4 times (e.g. over the course of several months or years. For some applications, the formulation may be administered at predefined intervals of more than 3 months and/or less than 24 months, such as 3-24 months, e.g. 6-24 months, e.g. 6-18 months or 12-24 months. For example, a second dose of the formulation may be administered 12-18 months after a first dose has been administered.

[0341] For some applications, a formulation may be provided that comprises a predefined amount of the virus, such as greater than lxlO^A2 plaque-forming units (PFU) and/or less than lxl0^A10 PFU, e.g., 1X10^A2-1X10^A10 PFU (e.g., 1X10^A2-1X10^A8 PFU, such as lxlO^A2- lxlO^A6 PFU, such as 1X10^A3- 1X10^A5 PFU, such as approximately lxlO^A4 PFU; or lxlO^A4- lxl0^A10 PFU, such as 1X10^A4- 1X10^A8 PFU, such as 1X10^A6- 1X10^A8 PFU). [0342] For some applications, one or more penetrants may be included in the formulation, e.g., to facilitate transmucosal penetration. Such penetrants may include, for example, detergents, bile salts, and/or fusidic acid derivatives.

[0343] For some applications, the formulation may be lyophilized. For some applications, the formulation may comprise one or more stabilizers, e.g., sucrose, sorbitol, trehalose, saccharin, and/or polyethylene glycol (PEG).

[0344] For some applications, e.g., for some applications in which the formulation contains a live pathogen, the formulation may be provided in a frozen state. For some such applications, the user (e.g. the medical practitioner) thaws the formulation in advance of (e.g. immediately prior to) administration. For some applications, the formulation is administered while frozen. For some such applications, the formulation is administered at approximately 0 degrees C.

[0345] The protocol may include a pre-administration portion including an overnight fast and/or a warm water enema to clear fecal matter prior to inoculation.

[0346] In some applications, the pathogen may be a coronavirus, e.g., SARS-CoV-2.

[0347] In some applications, the pathogen may be a respiratory virus. In some applications, the respiratory virus may be a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus (e.g. PIV-1, PIV-2, or PIV-3), a metapneumo virus (MPV), or an influenza virus.

[0348] In some applications, the pathogen may be a central nervous system (CNS) virus. In some applications, the CNS virus may be an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), or a varicella zoster virus (VZV).

[0349] For some applications, the pathogen may be a cytomegalovirus (CMV).

[0350] For some applications, the pathogen may be an Epstein-Barr Virus (EBV).

[0351] In some applications, the pathogen may be a non- viral pathogen (e.g. a bacterial pathogen or a fungal pathogen), affecting a system other than the gastrointestinal system, e.g., the respiratory system, the CNS, the circulatory system, the upper gastrointestinal tract, or the lymphatic system.

[0352] For some applications, the nonviral pathogen may be a bacterial pathogen such as Helicobacter pylori, a streptococcus, or Neisseria meningitidis. [0353] For some applications in which the pathogen is a virus, a heat- sensitive strain of the virus is used. For example, for some applications in which the pathogen is SARS-CoV-2, a strain having, compared to the Wuhan strain (NC_045512), one or more of the following nucleotide substitutions:

G18782T (in coding sequence for protein NSP14),

G19285A (in coding sequence for protein NSP14),

C19550T (in coding sequence for protein NSP14),

C24198T (in coding sequence for spike protein),

T26327C (in coding sequence for envelope protein),

C28278T (in coding sequence for nucleocapsid protein); and/or one or more of the following amino acid substitutions

G248V (in protein NSP14),

G416S (in protein NSP14),

A504V (in protein NSP14),

A879V (in spike protein),

L28P (in envelope protein),

S2F (in nucleocapsid protein).

[0354] For some such applications, such a strain is the A50-18 strain, described in Okamura, Shinya, et al. "Live attenuated SARS-CoV-2 vaccine candidate: Protective immunity without serious lung lesions in Syrian hamsters." bioRxiv (2021) (DOI 10.1101/2021.02.15.430863), which is incorporated herein by reference.

[0355] In some applications in which the pathogen is a virus, the formulation may comprise a live form of the virus. In some applications, such a live form may be unattenuated and/or unmodified. In some applications, such a live form of the virus may be unencapsulated (e.g. may have been unencapsulated for use in the formulation) - e.g. to facilitate cellular entry, such as entry into cells that the virus does not typically encounter in the natural progression of the disease, and/or to increase safety of the formulation due to reduced viability /longevity of the virus outside of a host. In some applications, the formulation may comprise an attenuated form of the virus, a heat- sensitive form of the virus, or an inactive form of the virus. The inactive form of the virus may be a heat-killed and/or chemically-inactivated virus. The inactive form may comprise viral antigens and/or a nucleic acid encoding specific viral antigens.

[0356] For some applications, the rectally-administered virus is a recombinant virus that encodes an epitope that stimulates an immune response to a pathogen. For such applications, the recombinant virus (i.e. the "host" virus - e.g. in its wild-type non-recombinant form) is itself a pathogen, whereas for other applications it is substantially non-pathogenic. For some applications, the encoded epitope is an epitope of the pathogen against which the stimulated immune response is desired. For example, nucleic acid from that pathogen may be spliced into the nucleic acid of the host virus to generate the recombinant virus. For some applications, the host virus is an influenza virus. For some applications, the epitope is an epitope of HIV.

[0357] Reference is now made to Figs. 2A-B, 3A-B, 4, 5, and 6, which are schematic illustrations of various formulations 110 of the pathogen, in various formats and/or means of application thereof, in accordance with some applications.

[0358] In some applications, and as shown in Figs. 2A-B, formulation 110 is provided as an enema formulation 110A. For such applications, enema formulation 110A may comprise an emulsion, a liquid solution, or a suspension.

[0359] For some applications, formulation 110A is provided in the format of an enema (e.g., an enema applicator) 30. Enema 30 may comprise a bottle 31 and an applicator tube 32 that may be provided pre-connected to the bottle, or, as shown, may be provided separated from the bottle. For some applications, applicator tube 32 may be provided with one or more pins, teeth, or other piercing or cutting elements 34 for penetrating a seal 33 on bottle 31 - e.g., upon attaching and/or tightening the tube to the bottle.

[0360] For some applications, formulation 110A may be stored in a lyophilized state within bottle 31 (Fig. 2A), in order to preserve the viability and/or longevity of the formulation. This lyophilized state is represented in Fig. 2A by reference numeral 110A'. The formulation may be reconstituted within bottle 31 (Fig. 2B) prior to administration.

[0361] For some applications, formulation 110A may be stored frozen within bottle 31, and is thawed prior to administration.

[0362] In some applications, and as shown in Figs. 3A-B, formulation 110 is provided either as a swab 40A (e.g. a handle-and-tip swab), or as a wipe 40B (e.g. a swab in the style of a wipe) comprising formulation HOB. Swab 40A and wipe 40B may be for (e.g. may be configured for) rectal application - e.g. rectal administration of formulation HOB.

[0363] Swab 40A may comprise a handle 42 and a tip 44. In some applications, tip 44 may be detachable from handle 42.

[0364] Wipe 40B may comprise a flexible sheet 45 (e.g. a sheet of fabric).

[0365] Swab 40A may be provided with tip 44 (and optionally also handle 42) enclosed within a sealed wrapping 46 - e.g. a sealed wrapping 46A. Wipe 40B may be provided fully enclosed within a sealed wrapping 46 - e.g. a sealed wrapping 46B. Wrapping 46 (e.g. wrapping 46A and/or wrapping 46B) may be frangible in order to facilitate the user exposing formulation HOB before use.

[0366] For some applications, wrapping 46 (e.g. wrapping 46A and/or wrapping 46B) is configured to be soluble, absorbable, or otherwise degradable in/by the rectum in a manner that facilitates rectal insertion with the wrapper in place. It is hypothesized that such a configuration may increase safety by reducing a likelihood of contaminating the local environment with the pathogen.

[0367] Formulation HOB may be a gel (e.g. a hydrogel and/or a polymeric gel). For some applications, tip 44 may be porous (e.g. may comprise a sponge), and the gel may be infiltrated into the tip. For some applications, sheet 45 may comprise a permeable, absorptive, or porous material, into which formulation HOB may be infiltrated.

[0368] Swab 40A and/or wipe 40B may be biodegradable.

[0369] In some applications, and as shown in Figs. 4-6, formulation 110 is provided as a suppository formulation 110C. For some such applications, formulation 110C is provided in the format of a suppository 50 for rectal administration. Suppository 50 typically comprises a capsule 51 and a core 52. Formulation HOC may be disposed in core 52.

[0370] Capsule 51 may be formed from a solid with a melting point near or below human body temperature, such as cocoa butter, polyethylene glycol, a hydrogel, glycerinated gelatin, and/or other glycerides.

[0371] For some applications, capsule 51 comprises a lid 54, which may facilitate introduction of formulation 110C, either at the time of manufacture or immediately prior to administration of the suppository. [0372] Core 52 (and lid 54, if present) may comprise a non-irritating excipient that may have a melting temperature of between 25 and 37 degrees C - i.e., such that it melts in the rectum to deliver the pathogen.

[0373] Fig. 4 shows a suppository 50A, which is a variant of suppository 50. Suppository 50A comprises a capsule 51A (which is a variant of capsule 51), and a core 52A (which is a variant of core 52). Suppository 50A is typically provided with formulation HOC in core 52A.

[0374] Fig. 5 shows a suppository 50B, which is a variant of suppository 50. Suppository 50B is typically similar to suppository 50A, except for the inclusion of a reporter dye 53. It is to be noted that other formulations may also utilize reporter dye 53, mutatis mutandis.

[0375] Reporter dye 53 is hypothesized to facilitate verification that formulation HOC has been administered/received. For example, subsequently to administering suppository 50B, a presence of the reporter dye, e.g., at the perianal area, or in the stool, is hypothesized to be indicative that the contents (e.g. the formulation) of the suppository were successfully released from the capsule. A user (e.g. a medical professional and/or the recipient of the suppository) may check for the presence of the reporter dye once, or more than once - e.g., at predefined intervals after administration.

[0376] It is to be noted that, in this context, the term "dye" is intended to include pigments and/or other colorants. In some applications, dye 53 is a strongly colored biocompatible dye, e.g., methylene blue, indigo carmine, turmeric extract, or beet extract. In some applications, dye 53 may be a fluorescent dye that is visualized using a light source outside of the visual spectrum, e.g., ultraviolet. In some applications, dye 53 may be luminous - e.g. chemiluminescent.

[0377] In some applications, dye 53 may be configured to be poorly absorbed by the gastrointestinal tract. For example, the reporter dye may be bound to and/or encapsulated in microbeads.

[0378] For some applications, and as shown, suppository 50B may include reporter dye 53 as a discrete layer - e.g. disposed between capsule 51B and core 52B. In some applications, e.g., those in which the suppository comprises discrete layers, the suppository may be produced by serial layer manufacturing or by additive manufacturing. In some such applications in which the reporter dye 53 is present as a discrete layer, the active ingredient may be encapsulated into the capsule as a solid insert, and the reporter dye subsequently injected between the capsule and the solid insert.

[0379] For some applications, dye 53 may be included within core 52 - e.g. mixed with the pathogen. For example, formulation HOC may be prepared by mixing dye 53 in with the pathogen. As described hereinabove, dye 53 may serve as an indicator of success of administration.

[0380] For some applications, dye 53 may be included within capsule 51.

[0381] In some applications, the reporter dye may additionally or alternatively be used as a safety feature to indicate spread of the virus outside of the subject or outside of the gastrointestinal tract.

[0382] It is to be noted that reporter dye 53 may be used in rectally-administered formulations (e.g. suppositories) other than those containing, or for administration of, a pathogen. That is, dye 53 may be used to report delivery of any active ingredient (e.g. therapeutic ingredient) such as a drug, a biomolecule, or a vaccine. Furthermore, although the present disclosure primarily relates to rectal administration, non-rectal (e.g. vaginal) suppositories may be augmented by the use of reporter dye 53, mutatis mutandis.

[0383] Reference is now further made to Fig. 7, which is a flowchart showing at least some steps of a method 20 for use with a suppository containing a reporter dye, in accordance with some applications.

[0384] Following identifying the subject (step 22), a suppository having a reporter dye or pigment is administered (step 24). Subsequently, a user (e.g., a medical professional and/or the recipient of the suppository) checks for the presence of the reporter dye at the perianal area. Hence step 26 comprises observing a presence of the reporter dye - e.g., by wiping the perianal area with tissue or other disposable paper product. The method may end after step 26, or optionally may continue to step 28, in which testing is performed to detect a presence of antibodies to the pathogen in the blood or other fluid of the subject. The testing may be performed a specific time interval, or multiple intervals, after step 26.

[0385] It is noted that, although step 26 is typically performed at a predetermined time after step 24 (e.g., according to a time at which the capsule of the suppository is expected to release its contents), steps 24 and 28 may be performed significantly later than the preceding step - e.g. with a delay of days, weeks, or months following the preceding step. [0386] Fig. 6 shows a suppository 50C, which is a variant of suppository 50. Suppository 50C may be similar to suppository 50A, except that, within a capsule 51C (i.e. a variant of capsule 51), a hollow core 52C (i.e. a variant of core 52) may be absent of a pathogen formulation. Core 52C is configured to receive the pathogen formulation soon (e.g. immediately) before administration - e.g. the user may inject pathogen formulation HOC through capsule 51C into the core. For some applications, suppository 50C may be provided with core 52C containing a cellular suspension and/or culture medium (e.g., Minimal Essential Medium; MEM), into which the pathogen is to be injected prior to use.

[0387] In some applications, suppository 50 may be formed for controlled release of the pathogen or other active ingredient. For example, in some applications, the formulation may comprise synthetic or biological mucus - e.g., mucins comprising high molecular weight glycoproteins such as O-linked glycans. High molecular weight glycoproteins may slow down the ability of the pathogen to penetrate cells of the subject and thereby slow infection of the subject by the pathogen. A slower infection rate may advantageously allow the subject to mount an immune response while moderating undesirable symptoms of illness.

[0388] In some applications, the formulation may comprise mucus excretion modulators that regulate (e.g. induce) mucus secretion. Such modulators may be derived from goblet cell extracts, or may be synthetic pharmaceuticals. The specific mucins or modulators in a given formulation may be adapted to control the rate of release of the specific pathogen in the formulation.

[0389] Reference is again made to Figs. 1-7. In applications in which a live or attenuated virus is an active ingredient in the formulation, the formulation and/or the format (e.g., the core of a suppository) may further comprise cells (e.g., host cells) to support growth and replication of the live virus. In such applications, a cell-culture medium, e.g., MEM, may be included in the formulation. In some such applications (e.g., applications in which unencapsulated virus particles are desirable), the formulation may comprise multiple viral host cell types having different metabolic rates and/or supporting different rates of viral replication. The presence of such multiple cell types may increase the presence of unencapsulated particles at any given time - e.g. such that a sufficient quantity of unencapsulated particles is present in the formulation at the time of administration to the subject.

[0390] In some applications, a formulation that includes a virus may further include cells that are capable of supporting replication of viral nucleic acid and/or proteins, but that is incapable of supporting production and/or shedding (e.g. budding) of viable viral particles from the cell. For some applications, such in/capabilities are provided by genetic modification of these cells. Alternatively or additionally, such in/capabilities are provided by a medium in which the cells are disposed. For example, the medium may lack one or more components required for production and/or shedding of viable viral particles, and/or may comprise an inhibitor of viral production and/or shedding.

[0391] It is to be noted that, although formulations disclosed herein are generally described as comprising a single pathogen, for some applications formulations may comprise more than one pathogen. For example, a formulation may comprise more than one respiratory pathogen/virus, more than one CNS pathogen/virus, more than one circulatory system pathogen/virus, or more than one lymphatic system pathogen/virus. Furthermore, a formulation may combine pathogens/viruses that infect/affect different ones of these systems. For example, a formulation may comprise a CNS pathogen/virus and a respiratory system pathogen/virus.

[0392] It is hypothesized that, for some applications, an enema format may advantageously expose the pathogen more immediately to a larger surface area of the gastrointestinal tract lining, thereby facilitating adhesion and uptake of the immunogenic component of the formulation. It is hypothesized that, for some applications, a gel or solid format (e.g. a suppository or a swab) may advantageously provide improved handling and/or containment of the pathogen.

[0393] Further potential advantages of providing (i.e. making available) multiple formats and/or formulations include the ability to select a format and/or formulation according to a desired depth of insertion into the rectum, and/or a desired extent and/or rate of exposure of the gastrointestinal tract to the virus. For example, in some applications, a slower-release format (e.g. a suppository) and/or formulation may be particularly suitable for children, infants, and/or otherwise vulnerable (e.g. immunocompromised) individuals. In some applications (e.g. for a subject who is known to have had a recent natural/unintended exposure to the pathogen or an infected individual) a large volume enema format and/or a faster-acting formulation may be particularly desirable.

[0394] Reference is again made to Figs. 1-7. It is hypothesized by the inventor that a further advantage to rectal administration relates to safety. Should it be determined, postadministration, that it may be desirable to prematurely terminate exposure of the pathogen to a given subject (e.g. due to the subject developing undesirable side-effects), salvage treatments may be possible. For example, flushing the rectum (e.g. using a detergent solution and/or an alcohol), rectal administration of antimicrobial radiation (e.g. UV light), rectal administration of an antimicrobial substance (e.g. an alcohol and/or a pharmaceutical), and/or rectal application of heat or cold (e.g. of a heated or cooled liquid) - e.g. in order to reduce the viral burden in the rectum. Alternatively or additionally, an antipathogenic pharmacologic agent may be administered rectally and/or systemically.

[0395] Example Applications (some non-limiting examples of the concepts herein are recited below):

[0396] Example 1. A wipe, formulated for rectal administration, and comprising a respiratory virus.

[0397] Example 2. The wipe according to example 1, further comprising a suspension of cells supportive of the respiratory virus.

[0398] Example 3. The wipe according to any one of examples 1-2, wherein the wipe comprises a swab-compatible gel.

[0399] Example 4. The wipe according to any one of examples 1-3, wherein the wipe comprises a polymeric material.

[0400] Example 5. The wipe according to any one of examples 1-4, wherein the respiratory virus is unencapsulated.

[0401] Example 6. The suppository according to any one of examples 1-5, wherein the respiratory virus is an RNA virus.

[0402] Example 7. The suppository according to any one of examples 1-6, wherein the respiratory virus is an influenza virus.

[0403] Example 8. The suppository according to any one of examples 1-7, wherein the respiratory virus is a coronavirus.

[0404] Example 9. The wipe according to example 8, wherein the respiratory virus is SARS-CoV-Example 2.

[0405] Example 10. The wipe according to any one of examples 1-9, wherein the respiratory virus is live.

[0406] Example 11. The wipe according to any one of examples 1-10, wherein the respiratory virus is heat inactivated. [0407] Example 12. The wipe according to any one of examples 1-11, wherein the respiratory virus is heat-sensitive.

[0408] Example 13. The wipe according to any one of examples 1-12, wherein the respiratory virus is chemically inactivated.

[0409] Example 14. The wipe according to any one of examples 1-13, wherein the wipe is maintained in a frozen state until administration.

[0410] Example 15. The wipe according to any one of examples 1-14, wherein the respiratory virus is attenuated.

[0411] Example 16. The wipe according to any one of examples 1-15, further comprising lyophilization stabilizers.

[0412] Example 17. The wipe according to any one of examples 1-16, further comprising penetrants.

[0413] Example 18. The wipe according to any one of examples 1-17, wherein the wipe comprises the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0414] Example 19. The wipe according to example 18, wherein the wipe comprises the respiratory virus at approximately lxlO^A4 PFU per dose.

[0415] Example 20. A suppository, formulated for rectal administration, and comprising a respiratory virus.

[0416] Example 21. The suppository according to example 20, further comprising a suspension of cells supportive of the respiratory virus.

[0417] Example 22. The suppository according to any one of examples 20-21, wherein the respiratory virus is selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus.

[0418] Example 23. The suppository according to any one of examples 20-22, wherein the suppository comprises a layered capsule.

[0419] Example 24. The suppository according to any one of examples 20-23, wherein the respiratory virus is unencapsulated.

[0420] Example 25. The suppository according to any one of examples 20-24, wherein the respiratory virus is an RNA virus. [0421] Example 26. The suppository according to any one of examples 20-25, wherein the respiratory virus is an influenza virus.

[0422] Example 27. The suppository according to any one of examples 20-26, wherein the respiratory virus is a coronavirus.

[0423] Example 28. The suppository according to example 27, wherein the coronavirus virus is SARS-CoV-Example 2.

[0424] Example 29. The suppository according to any one of examples 20-28, wherein the respiratory virus is live.

[0425] Example 30. The suppository according to any one of examples 20-29, wherein the respiratory virus is heat inactivated.

[0426] Example 31. The suppository according to any one of examples 20-30, wherein the respiratory virus is heat-sensitive.

[0427] Example 32. The suppository according to any one of examples 20-31, wherein the respiratory virus is chemically inactivated.

[0428] Example 33. The suppository according to any one of examples 20-32, wherein the suppository is maintained in a frozen state until administration.

[0429] Example 34. The suppository according to any one of examples 20-33, wherein the respiratory virus is attenuated.

[0430] Example 35. The suppository according to any one of examples 20-34, further comprising lyophilization stabilizers.

[0431] Example 36. The suppository according to any one of examples 20-35, further comprising penetrants.

[0432] Example 37. The suppository according to any one of examples 20-36, further comprising a high molecular weight glycoprotein.

[0433] Example 38. The suppository according to any one of examples 20-37, wherein the suppository comprises the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0434] Example 39. The suppository according to example 38, wherein the suppository comprises the respiratory virus at approximately lxlO^A4 PFU per dose. [0435] Example 40. A method, comprising: identifying a human subject to be inoculated with a coronavirus; and, responsively to the identifying, inoculating the subject with the coronavirus by rectally administering, to the subject, a formulation including the coronavirus.

[0436] Example 41. The method according to example 40, wherein the formulation includes a suspension of cells supportive of the coronavirus, and wherein rectally administering the formulation comprises rectally administering the formulation that includes the suspension of cells supportive of the coronavirus.

[0437] Example 42. The method according to any one of examples 40-41, wherein inoculating the subject with the coronavirus by rectally administering the coronavirus comprises rectally administering a formulation including coronavirus SARS-CoV-Example 2.

[0438] Example 43. The method according to any one of examples 40-42, wherein rectally administering the formulation comprising the coronavirus comprises rectally administering lxlO^A2 to lxl0^A10 plaque forming units of the coronavirus to the subject.

[0439] Example 44. The method according to any one of examples 40-43, wherein the coronavirus being taken up by at least one cell in a gastrointestinal tract of the subject induces a systemic immune response to the coronavirus in the subject.

[0440] Example 45. The method according to any one of examples 40-44, wherein rectally administering the formulation comprises rectally administering the formulation in an enema formulation.

[0441] Example 46. The method according to any one of examples 40-45, wherein rectally administering the formulation comprises rectally administering the formulation using a swab applicator.

[0442] Example 47. The method according to any one of examples 40-46, wherein rectally administering the formulation comprises rectally administering the formulation using a wet- wipe-style device.

[0443] Example 48. The method according to any one of examples 40-47, wherein rectally administering the formulation comprises rectally administering the formulation in a suppository. [0444] Example 49. The method according to example 48, wherein rectally administering the formulation in the suppository comprises rectally administering the formulation in a suppository comprising a reporter dye.

[0445] Example 50. The method according to example 49, further comprising checking for a presence of the reporter dye.

[0446] Example 51. The method according to any one of examples 40-50, wherein rectally administering the formulation comprises rectally administering a first dose of the formulation, and wherein the method further comprises rectally administering a second dose of the formulation.

[0447] Example 52. The method according to example 51, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 12-18 months after rectally administering the first dose of the formulation.

[0448] Example 53. The method according to example 51, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 3-24 months after rectally administering the first dose of the formulation.

[0449] Example 54. The method according to example 53, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 6-24 months after rectally administering the first dose of the formulation.

[0450] Example 55. The method according to example 54, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 12-24 months after rectally administering the first dose of the formulation.

[0451] Example 56. The method according to example 54, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 6-18 months after rectally administering the first dose of the formulation.

[0452] Example 57. A method, comprising: identifying a human subject to be inoculated with a central nervous system (CNS) virus; and, responsively to the identifying, inoculating the subject with the CNS virus by rectally administering, to the subject, a formulation comprising the CNS virus.

[0453] Example 58. The method according to example 57, wherein the formulation includes a suspension of cells supportive of the CNS virus, and wherein rectally administering the formulation comprises rectally administering the formulation that includes the suspension of cells supportive of the CNS virus.

[0454] Example 59. The method according to any one of examples 57-58, wherein inoculating the subject with the CNS virus by rectally administering the CNS virus comprises rectally administering a formulation comprising at least one CNS virus selected from the group consisting of: an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), and a varicella zoster virus (VZV).

[0455] Example 60. The method according to any one of examples 57-59, wherein rectally administering the formulation comprising the CNS virus comprises rectally administering lxlO^A2 to lxl0^A10 plaque forming units of the CNS virus to the subject.

[0456] Example 61. The method according to any one of examples 57-60, wherein the CNS virus being taken up by at least one cell in a gastrointestinal tract of the subject induces a systemic immune response to the CNS virus in the subject.

[0457] Example 62. The method according to any one of examples 57-61, wherein rectally administering the formulation comprises rectally administering the formulation in an enema formulation.

[0458] Example 63. The method according to any one of examples 57-62, wherein rectally administering the formulation comprises rectally administering the formulation using a swab applicator.

[0459] Example 64. The method according to any one of examples 57-63, wherein rectally administering the formulation comprises rectally administering the formulation using a wet- wipe-style device.

[0460] Example 65. The method according to any one of examples 57-64, wherein rectally administering the formulation comprises rectally administering the formulation in a suppository.

[0461] Example 66. The method according to example 65, wherein rectally administering the formulation in the suppository comprises rectally administering the formulation in a suppository comprising a reporter dye.

[0462] Example 67. The method according to example 66, further comprising checking for a presence of the reporter dye. [0463] Example 68. The method according to any one of examples 57-67, wherein rectally administering the formulation comprises rectally administering a first dose of the formulation, and wherein the method further comprises rectally administering a second dose of the formulation.

[0464] Example 69. The method according to example 68, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 12-18 months after rectally administering the first dose of the formulation.

[0465] Example 70. The method according to example 68, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 3-24 months after rectally administering the first dose of the formulation.

[0466] Example 71. The method according to example 70, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 6-24 months after rectally administering the first dose of the formulation.

[0467] Example 72. The method according to example 71, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 12-24 months after rectally administering the first dose of the formulation.

[0468] Example 73. The method according to example 71, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 6-18 months after rectally administering the first dose of the formulation.

[0469] Example 74. A method, comprising: identifying a human subject to be inoculated with a respiratory virus; and, responsively to the identifying, inoculating the subject with the respiratory virus by rectally administering, to the subject, a formulation comprising the respiratory virus.

[0470] Example 75. The method according to example 74, wherein the formulation includes a suspension of cells supportive of the respiratory virus, and wherein rectally administering the formulation comprises rectally administering the formulation that includes the suspension of cells supportive of the respiratory virus.

[0471] Example 76. The method according to any one of examples 74-75, wherein inoculating the subject with the respiratory virus by rectally administering the respiratory virus comprises rectally administering a formulation comprising at least one respiratory virus selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus.

[0472] Example 77. The method according to any one of examples 74-76, wherein rectally administering the formulation comprising the respiratory virus comprises rectally administering lxlO^A2 to lxl0^A10 plaque forming units of the respiratory virus to the subject.

[0473] Example 78. The method according to any one of examples 74-77, wherein the respiratory virus being taken up by at least one cell in a gastrointestinal tract of the subject induces a systemic immune response to the respiratory virus in the subject.

[0474] Example 79. The method according to any one of examples 74-78, wherein rectally administering the formulation comprises rectally administering the formulation in an enema formulation.

[0475] Example 80. The method according to any one of examples 74-79, wherein rectally administering the formulation comprises rectally administering the formulation using a swab applicator.

[0476] Example 81. The method according to any one of examples 74-80, wherein rectally administering the formulation comprises rectally administering the formulation using a wet- wipe-style device.

[0477] Example 82. The method according to any one of examples 74-81, wherein rectally administering the formulation comprises rectally administering the formulation in a suppository.

[0478] Example 83. The method according to example 82, wherein rectally administering the formulation in the suppository comprises rectally administering the formulation in a suppository comprising a reporter dye.

[0479] Example 84. The method according to example 83, further comprising checking for a presence of the reporter dye.

[0480] Example 85. The method according to any one of examples 74-84, wherein rectally administering the formulation comprises rectally administering a first dose of the formulation, and wherein the method further comprises rectally administering a second dose of the formulation. [0481] Example 86. The method according to example 85, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 12-18 months after rectally administering the first dose of the formulation.

[0482] Example 87. The method according to example 85, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 3-24 months after rectally administering the first dose of the formulation.

[0483] Example 88. The method according to example 87, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 6-24 months after rectally administering the first dose of the formulation.

[0484] Example 89. The method according to example 88, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 12-24 months after rectally administering the first dose of the formulation.

[0485] Example 90. The method according to example 88, wherein rectally administering the second dose of the formulation comprises rectally administering the second dose of the formulation 6-18 months after rectally administering the first dose of the formulation.

[0486] Example 91. An enema formulation comprising a coronavirus.

[0487] Example 92. The enema formulation according to 93, further comprising a suspension of cells supportive of the coronavirus.

[0488] Example 93. The enema formulation according to any one of examples 91-92, wherein the enema formulation comprises an emulsion.

[0489] Example 94. The enema formulation according to any one of examples 91-93, wherein the enema formulation comprises a solution.

[0490] Example 95. The enema formulation according to any one of examples 91-94, wherein the enema formulation comprises a suspension.

[0491] Example 96. The enema formulation according to any one of examples 91-95, wherein the enema formulation comprises a liquid.

[0492] Example 97. The enema formulation according to any one of examples 91-96, wherein the coronavirus is unencapsulated.

[0493] Example 98. The enema formulation according to any one of examples 91-97, wherein the coronavirus is SARS-CoV-Example 2. [0494] Example 99. The enema formulation according to any one of examples 91-98, wherein the coronavirus is live.

[0495] Example 100. The enema formulation according to any one of examples 91-99, wherein the coronavirus is heat inactivated.

[0496] Example 101. The enema formulation according to any one of examples 91-100, wherein the coronavirus is heat-sensitive.

[0497] Example 102. The enema formulation according to any one of examples 91-101, wherein the coronavirus is chemically inactivated.

[0498] Example 103. The enema formulation according to any one of examples 91-102, wherein the enema formulation is maintained in a frozen state until administration.

[0499] Example 104. The enema formulation according to any one of examples 91-103, wherein the coronavirus is attenuated.

[0500] Example 105. The enema formulation according to any one of examples 91-104, further comprising lyophilization stabilizers.

[0501] Example 106. The enema formulation according to any one of examples 91-105, further comprising penetrants.

[0502] Example 107. The enema formulation according to any one of examples 91-106, wherein the enema formulation comprises the coronavirus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0503] Example 108. The enema formulation according to example 107, wherein the enema formulation comprises the coronavirus at approximately lxlO^A4 PFU per dose.

[0504] Example 109. An enema formulation comprising an Epstein-Barr virus (EBV).

[0505] Example 110. An enema formulation comprising a cytomegalovirus (CMV).

[0506] Example 111. An enema formulation comprising Helicobacter pylori.

[0507] Example 112. A suppository, formulated for rectal administration, and comprising a coronavirus.

[0508] Example 113. The suppository according to example 112, further comprising a suspension of cells supportive of the coronavirus. [0509] Example 114. The suppository according to any one of examples 112-113, wherein the suppository comprises a layered capsule.

[0510] Example 115. The suppository according to any one of examples 112-114, wherein the coronavirus is unencapsulated.

[0511] Example 116. The suppository according to any one of examples 112-115, wherein the coronavirus is SARS-CoV-Example 2.

[0512] Example 117. The suppository according to any one of examples 112-116, wherein the coronavirus is live.

[0513] Example 118. The suppository according to any one of examples 112-117, wherein the coronavirus is heat inactivated.

[0514] Example 119. The suppository according to any one of examples 112-118, wherein the coronavirus is heat-sensitive.

[0515] Example 120. The suppository according to any one of examples 112-119, wherein the coronavirus is chemically inactivated.

[0516] Example 121. The suppository according to any one of examples 112-120, wherein the suppository is maintained in a frozen state until administration.

[0517] Example 122. The suppository according to any one of examples 112-121, wherein the coronavirus is attenuated.

[0518] Example 123. The suppository according to any one of examples 112-122, further comprising lyophilization stabilizers.

[0519] Example 124. The suppository according to any one of examples 112-123, further comprising penetrants.

[0520] Example 125. The suppository according to any one of examples 112-124, wherein the suppository comprises the coronavirus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0521] Example 126. The suppository according to example 125, wherein the suppository comprises the coronavirus at approximately lxlO^A4 PFU per dose.

[0522] Example 127. A suppository, formulated for rectal administration, and comprising an Epstein-Barr virus (EBV). [0523] Example 128. A suppository, formulated for rectal administration, and comprising a cytomegalovirus (CMV).

[0524] Example 129. A suppository, formulated for rectal administration, and comprising Helicobacter pylori.

[0525] Example 130. A swab-compatible gel, formulated for rectal administration, and comprising a coronavirus.

[0526] Example 131. The swab-compatible gel according to example 130, further comprising a suspension of cells supportive of the coronavirus.

[0527] Example 132. The swab-compatible gel according to any one of examples 130-131, wherein the swab-compatible gel comprises a polymer.

[0528] Example 133. The swab-compatible gel according to any one of examples 130-132, wherein the coronavirus is unencapsulated.

[0529] Example 134. The swab-compatible gel according to any one of examples 130-133, wherein the coronavirus is SARS-CoV-Example 2.

[0530] Example 135. The swab-compatible gel according to any one of examples 130-134, wherein the coronavirus is live.

[0531] Example 136. The swab-compatible gel according to any one of examples 130-135, wherein the coronavirus is heat inactivated.

[0532] Example 137. The swab-compatible gel according to any one of examples 130-136, wherein the coronavirus is heat-sensitive.

[0533] Example 138. The swab-compatible gel according to any one of examples 130-137, wherein the coronavirus is chemically inactivated.

[0534] Example 139. The swab-compatible gel according to any one of examples 130-138, wherein the swab-compatible gel is maintained in a frozen state until administration.

[0535] Example 140. The swab-compatible gel according to any one of examples 130-139, wherein the coronavirus is attenuated.

[0536] Example 141. The swab-compatible gel according to any one of examples 130-140, further comprising lyophilization stabilizers.

[0537] Example 142. The swab-compatible gel according to any one of examples 130-141, further comprising penetrants. [0538] Example 143. The swab-compatible gel according to any one of examples 130-142, wherein the swab-compatible gel comprises the coronavirus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0539] Example 144. The swab-compatible gel according to example 104, wherein the swab-compatible gel comprises the coronavirus at approximately lxlO^A4 PFU per dose.

[0540] Example 145. A swab-compatible gel, formulated for rectal administration, and comprising an Epstein-Barr virus (EBV).

[0541] Example 146. A swab-compatible gel, formulated for rectal administration, and comprising a cytomegalovirus (CMV).

[0542] Example 147. A swab-compatible gel, formulated for rectal administration, and comprising Helicobacter pylori.

[0543] Example 148. A wipe, formulated for rectal administration, and comprising an Epstein-Barr virus (EBV).

[0544] Example 149. A wipe, formulated for rectal administration, and comprising a cytomegalovirus (CMV).

[0545] Example 150. A wipe, formulated for rectal administration, and comprising Helicobacter pylori.

[0546] Example 151. A swab-compatible gel, formulated for rectal administration, and comprising a respiratory virus.

[0547] Example 152. The swab-compatible gel according to example 151, further comprising a suspension of cells supportive of the respiratory virus.

[0548] Example 153. The swab-compatible gel according to any one of examples 151-152, wherein the respiratory virus is selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus.

[0549] Example 154. The swab-compatible gel according to any one of examples 151-153, wherein the swab-compatible gel comprises a polymer.

[0550] Example 155. The swab-compatible gel according to any one of examples 151-154, wherein the respiratory virus is unencapsulated. [0551] Example 156. The swab-compatible gel according to any one of examples 151-155, wherein the respiratory virus is live.

[0552] Example 157. The swab-compatible gel according to any one of examples 151-156, wherein the respiratory virus is heat inactivated.

[0553] Example 158. The swab-compatible gel according to any one of examples 151-157, wherein the respiratory virus is heat-sensitive.

[0554] Example 159. The swab-compatible gel according to any one of examples 151-158, wherein the respiratory virus is chemically inactivated.

[0555] Example 160. The swab-compatible gel according to any one of examples 151-159, wherein the swab-compatible gel is maintained in a frozen state until administration.

[0556] Example 161. The swab-compatible gel according to any one of examples 151-160, wherein the respiratory virus is attenuated.

[0557] Example 162. The swab-compatible gel according to any one of examples 151-161, further comprising lyophilization stabilizers.

[0558] Example 163. The swab-compatible gel according to any one of examples 151-162, further comprising penetrants.

[0559] Example 164. The suppository according to any one of examples 151-163, further comprising a high molecular weight glycoprotein.

[0560] Example 165. The swab-compatible gel according to any one of examples 151-164, wherein the swab-compatible gel comprises the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0561] Example 166. The swab-compatible gel according to example 159, wherein the swab-compatible gel comprises the respiratory virus at approximately lxlO^A4 PFU per dose.

[0562] Example 167. An enema formulation comprising a respiratory virus.

[0563] Example 168. The enema formulation according to example 167, further comprising a suspension of cells supportive of the respiratory virus.

[0564] Example 169. The enema formulation according to any one of examples 167-168, wherein the respiratory virus is selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus. [0565] Example 170. The enema formulation according to any one of examples 167-169, wherein the enema formulation comprises an emulsion.

[0566] Example 171. The enema formulation according to any one of examples 167-170, wherein the enema formulation comprises a solution.

[0567] Example 172. The enema formulation according to any one of examples 167-171, wherein the enema formulation comprises a suspension.

[0568] Example 173. The enema formulation according to any one of examples 167-172, wherein the enema formulation comprises a liquid.

[0569] Example 174. The enema formulation according to any one of examples 167-173, wherein the respiratory virus is unencapsulated.

[0570] Example 175. The enema formulation according to any one of examples 167-174, wherein the respiratory virus is live.

[0571] Example 176. The enema formulation according to any one of examples 167-175, wherein the respiratory virus is heat inactivated.

[0572] Example 177. The enema formulation according to any one of examples 167-176, wherein the respiratory virus is heat-sensitive.

[0573] Example 178. The enema formulation according to any one of examples 167-177, wherein the respiratory virus is chemically inactivated.

[0574] Example 179. The enema formulation according to any one of examples 167-178, wherein the enema formulation is maintained in a frozen state until administration.

[0575] Example 180. The enema formulation according to any one of examples 167-179, wherein the respiratory virus is attenuated.

[0576] Example 181. The enema formulation according to any one of examples 167-180, further comprising lyophilization stabilizers.

[0577] Example 182. The enema formulation according to any one of examples 167-181, further comprising penetrants.

[0578] Example 183. The enema formulation according to any one of examples 167-182, further comprising a high molecular weight glycoprotein. [0579] Example 184. The enema formulation according to any one of examples 167-183, wherein the enema formulation comprises the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0580] Example 185. The enema formulation according to example 178, wherein the enema formulation comprises the respiratory virus at approximately lxlO^A4 PFU per dose.

[0581] Example 186. An enema formulation comprising a central nervous system (CNS) virus.

[0582] Example 187. The enema formulation according to example 186, further comprising a suspension of cells supportive of the CNS virus.

[0583] Example 188. The enema formulation according to any one of examples 186-187, wherein the enema formulation comprises an emulsion.

[0584] Example 189. The enema formulation according to any one of examples 186-188, wherein the enema formulation comprises a solution.

[0585] Example 190. The enema formulation according to any one of examples 186-189, wherein the enema formulation comprises a suspension.

[0586] Example 191. The enema formulation according to any one of examples 186-190, wherein the enema formulation comprises a liquid.

[0587] Example 192. The enema formulation according to any one of examples 186-191, wherein the CNS virus is unencapsulated.

[0588] Example 193. The enema formulation according to any one of examples 186-192, wherein the CNS virus comprises at least one CNS virus selected from the group consisting of: an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), and a varicella zoster virus (VZV).

[0589] Example 194. The enema formulation according to any one of examples 186-193, wherein the CNS virus is a first CNS virus, and wherein the enema formulation further comprises a second CNS virus.

[0590] Example 195. The enema formulation according to any one of examples 186-194, wherein the CNS virus is live.

[0591] Example 196. The enema formulation according to any one of examples 186-195, wherein the CNS virus is heat inactivated. [0592] Example 197. The enema formulation according to any one of examples 186-196, wherein the CNS virus is heat-sensitive.

[0593] Example 198. The enema formulation according to any one of examples 186-197, wherein the CNS virus is chemically inactivated.

[0594] Example 199. The enema formulation according to any one of examples 186-198, wherein the enema formulation is maintained in a frozen state until administration.

[0595] Example 200. The enema formulation according to any one of examples 186-199, wherein the CNS virus is attenuated.

[0596] Example 201. The enema formulation according to any one of examples 186-200, further comprising lyophilization stabilizers.

[0597] Example 202. The enema formulation according to any one of examples 186-201, further comprising penetrants.

[0598] Example 203. The enema formulation according to any one of examples 186-202, further comprising a high molecular weight glycoprotein.

[0599] Example 204. The enema formulation according to any one of examples 186-203, wherein the enema formulation comprises the CNS virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0600] Example 205. The enema formulation according to example 198, wherein the enema formulation comprises the CNS virus at approximately lxlO^A4 PFU per dose.

[0601] Example 206. A suppository, formulated for rectal administration, and comprising a central nervous system (CNS) virus.

[0602] Example 207. The suppository according to example 206, further comprising a suspension of cells supportive of the CNS virus.

[0603] Example 208. The suppository according to any one of examples 206-207, wherein the suppository comprises a layered capsule.

[0604] Example 209. The suppository according to any one of examples 206-208, wherein the CNS virus is unencapsulated.

[0605] Example 210. The suppository according to any one of examples 206-209, wherein the CNS virus comprises at least one CNS virus selected from the group consisting of: an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), and a varicella zoster virus (VZV).

[0606] Example 211. The suppository according to any one of examples 206-210, wherein the CNS virus is live.

[0607] Example 212. The suppository according to any one of examples 206-211, wherein the CNS virus is heat inactivated.

[0608] Example 213. The suppository according to any one of examples 206-212, wherein the CNS virus is heat-sensitive.

[0609] Example 214. The suppository according to any one of examples 206-213, wherein the CNS virus is chemically inactivated.

[0610] Example 215. The suppository according to any one of examples 206-214, wherein the suppository is maintained in a frozen state until administration.

[0611] Example 216. The suppository according to any one of examples 206-215, wherein the CNS virus is attenuated.

[0612] Example 217. The suppository according to any one of examples 206-216, further comprising lyophilization stabilizers.

[0613] Example 218. The suppository according to any one of examples 206-217, further comprising penetrants.

[0614] Example 219. The suppository according to any one of examples 206-218, further comprising a high molecular weight glycoprotein.

[0615] Example 220. The suppository according to any one of examples 206-219, wherein the suppository comprises the CNS virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0616] Example 221. The suppository according to example 220, wherein the suppository comprises the CNS virus at approximately lxlO^A4 PFU per dose.

[0617] Example 222. A swab-compatible gel, formulated for rectal administration, and comprising a central nervous system (CNS) virus.

[0618] Example 223. The swab-compatible gel according to example 222, further comprising a suspension of cells supportive of the CNS virus.

[0619] Example 224. The swab-compatible gel according to any one of examples 222-223, wherein the swab-compatible gel comprises a polymer. [0620] Example 225. The swab-compatible gel according to any one of examples 222-224, wherein the CNS virus is unencapsulated.

[0621] Example 226. The swab-compatible gel according to any one of examples 222-225, wherein the CNS virus comprises at least one CNS virus selected from the group consisting of: an enterovirus, an arbovirus, a herpes simplex virus (HSV), a human immunodeficiency virus (HIV), and a varicella zoster virus (VZV).

[0622] Example 227. The swab-compatible gel according to any one of examples 222-226, wherein the CNS virus is live.

[0623] Example 228. The swab-compatible gel according to any one of examples 222-227, wherein the CNS virus is heat inactivated.

[0624] Example 229. The swab-compatible gel according to any one of examples 222-228, wherein the CNS virus is heat-sensitive.

[0625] Example 230. The swab-compatible gel according to any one of examples 222-229, wherein the CNS virus is chemically inactivated.

[0626] Example 231. The swab-compatible gel according to any one of examples 222-230, wherein the swab-compatible gel is maintained in a frozen state until administration.

[0627] Example 232. The swab-compatible gel according to any one of examples 222-231, wherein the CNS virus is attenuated.

[0628] Example 233. The swab-compatible gel according to any one of examples 222-232, further comprising lyophilization stabilizers.

[0629] Example 234. The swab-compatible gel according to any one of examples 222-233, further comprising penetrants.

[0630] Example 235. The swab-compatible gel according to any one of examples 222-234, further comprising a high molecular weight glycoprotein.

[0631] Example 236. The swab-compatible gel according to any one of examples 222-235, wherein the swab-compatible gel comprises the CNS virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

[0632] Example 237. The swab-compatible gel according to example 230, wherein the swab-compatible gel comprises the CNS virus at approximately lxlO^A4 PFU per dose.

[0633] Example 238. A suppository for rectal administration, comprising: a capsule containing: an active ingredient; and a reporter dye.

[0634] Example 239. The suppository according to example 238, wherein the active ingredient is a vaccine.

[0635] Example 240. The suppository according to any one of examples 238-239, wherein the active ingredient is a drug.

[0636] Example 241. The suppository according to any one of examples 238-240, wherein the active ingredient is an antigen.

[0637] Example 242. The suppository according to any one of examples 238-241, wherein the active ingredient is an inactive virus.

[0638] Example 243. The suppository according to any one of examples 238-242, wherein the active ingredient is a live virus.

[0639] Example 244. The suppository according to any one of examples 238-243, wherein the active ingredient is nucleic acid encoding a viral antigen.

[0640] Example 245. The suppository according to any one of examples 238-244, wherein the active ingredient is a bacterial pathogen.

[0641] Example 246. The suppository according to any one of examples 238-245, wherein the reporter dye is fluorescent.

[0642] Example 247. The suppository according to any one of examples 238-246, wherein the reporter dye is methylene blue.

[0643] Example 248. The suppository according to any one of examples 238-247, wherein the reporter dye is indigo carmine.

[0644] Example 249. The suppository according to any one of examples 238-248, wherein the reporter dye is turmeric.

[0645] Example 250. The suppository according to any one of examples 238-249, wherein the reporter dye is beet extract.

[0646] Example 251. The suppository according to any one of examples 238-250, wherein the capsule comprises a polymer. [0647] Example 252. The suppository according to any one of examples 238-251, further comprising lyophilization stabilizers.

[0648] Example 253. The suppository according to any one of examples 238-252, further comprising penetrants.

[0649] Example 254. The suppository according to any one of examples 238-253, further comprising a high molecular weight glycoprotein.

[0650] Example 255. The suppository according to any one of examples 238-254, wherein the suppository is formulated such that the reporter dye comprises part of the capsule.

[0651] Example 256. The suppository according to any one of examples 238-255, wherein the capsule is produced by additive manufacturing.

[0652] Example 257. The suppository according to any one of examples 238-256, wherein the suppository is produced by additive manufacturing.

[0653] Example 258. The suppository according to any one of examples 238-257, wherein the capsule is produced by serial layer manufacturing.

[0654] Example 259. The suppository according to any one of examples 238-258, wherein the suppository is produced by serial layer manufacturing.

[0655] Example 260. The suppository according to any one of examples 238-259, wherein the capsule comprises a first layer and a second layer.

[0656] Example 261. The suppository according to example 260, wherein the first layer is an outer layer, and the second layer is an inner layer.

[0657] Example 262. The suppository according to example 261, wherein the outer layer comprises a polymeric substance.

[0658] Example 263. The suppository according to example 261, wherein the inner layer comprises the reporter dye.

[0659] Example 264. The suppository according to any one of examples 238-263, wherein the active ingredient is a live virus.

[0660] Example 265. The suppository according to example 264, wherein the live virus is maintained outside the capsule until administration.

[0661] Example 266. The suppository according to example 264, wherein the live virus is a heat- sensitive strain of SARS-CoV-Example 2. [0662] Example 267. The suppository according to example 264, wherein the capsule further comprises a suspension of cells supportive of the live virus.

[0663] Example 268. The suppository according to example 267, wherein the suspension of cells comprises a first viral host cell type and a second viral host cell type.

[0664] Example 269. The suppository according to example 268, wherein the first viral host cell type supports a different rate of viral replication compared with the second viral host cell type.

[0665] Example 270. A method, comprising: rectally administering a suppository to a subject, the suppository including a reporter dye; and, subsequently, checking for rectal presence of the reporter dye.

[0666] Example 271. The method according to example 270, wherein checking for rectal presence of the reporter dye is performed by wiping a perianal area of the subject with a disposable product and viewing the reporter dye on the disposable product.

[0667] Example 272. The method according to example 271, wherein wiping the perianal area with the disposable product comprises wiping the perianal area with a tissue.

[0668] Example 273. The method according to example 271, wherein wiping the perianal area with the disposable product comprises wiping the perianal area with a wipe.

[0669] Example 274. The method according to example 271, wiping the perianal area with the disposable product comprises wiping the perianal area with a swab.

[0670] Example 275. A method, comprising: identifying a subject that has been rectally administered with a suppository that includes a reporter dye; and, subsequently, checking for rectal presence of the reporter dye.

[0671] Example 276. The method according to example 275, wherein checking for rectal presence of the reporter dye is performed by wiping a perianal area of the subject with a disposable product and viewing the reporter dye on the disposable product.

[0672] Example 277. The method according to example 276, wherein wiping the perianal area with the disposable product comprises wiping the perianal area with a tissue.

[0673] Example 278. The method according to example 276, wherein wiping the perianal area with the disposable product comprises wiping the perianal area with a wipe. [0674] Example 279. The method according to example 276, wiping the perianal area with the disposable product comprises wiping the perianal area with a swab.

[0675] Example 280. A method, comprising: rectally receiving a suppository that includes a reporter dye; and, subsequently, checking for rectal presence of the reporter dye.

[0676] Example 281. The method according to example 280, wherein checking for rectal presence of the reporter dye is performed by wiping a perianal area of the subject with a disposable product and viewing the reporter dye on the disposable product.

[0677] Example 282. The method according to example 281, wherein wiping the perianal area with the disposable product comprises wiping the perianal area with a tissue.

[0678] Example 283. The method according to example 281, wherein wiping the perianal area with the disposable product comprises wiping the perianal area with a wipe.

[0679] Example 284. The method according to example 281, wiping the perianal area with the disposable product comprises wiping the perianal area with a swab.

[0680] Example 285. A method, comprising: providing an encapsulating material, a reporter dye, and an active ingredient; and, forming a suppository that includes the encapsulating material, the reporter dye, and the active ingredient.

[0681] Example 286. The method according to example 285, wherein forming the suppository comprises forming the suppository by additive manufacturing.

[0682] Example 287. The method according to any one of examples 285-286, wherein forming the suppository comprises forming the suppository by serial layer manufacturing.

[0683] Example 288. The method according to any one of examples 285-287, wherein the reporter dye includes methylene blue, and forming the suppository comprises forming the suppository that includes methylene blue.

[0684] Example 289. The method according to any one of examples 285-288, wherein the reporter dye includes carmine red, and forming the suppository comprises forming the suppository that includes carmine red.

[0685] Example 290. The method according to any one of examples 285-289, wherein the reporter dye includes a turmeric extract, and forming the suppository comprises forming the suppository that includes the turmeric extract. [0686] Example 291. The method according to any one of examples 285-290, wherein the reporter dye includes a beet extract, and forming the suppository comprises forming the suppository that includes the beet extract.

[0687] Example 292. The method according to any one of examples 285-291, wherein the reporter dye is fluorescent, and forming the suppository comprises forming the suppository that includes the fluorescent reporter dye.

[0688] Example 293. The method according to any one of examples 285-292, wherein the reporter dye is chemiluminescent, and forming the suppository comprises forming the suppository that includes the chemiluminescent reporter dye.

[0689] Example 294. The method according to any one of examples 285-293, wherein the reporter dye is encapsulated in microbeads, and forming the suppository comprises forming the suppository that includes the reporter dye that is encapsulated in microbeads.

[0690] Example 295. The method according to any one of examples 285-294, wherein the active ingredient includes a SARS-CoV-2 virus, and forming the suppository comprises forming the suppository that includes the SARS-CoV-2 virus.

[0691] Example 296. The method according to any one of examples 285-295, wherein the active ingredient includes a respiratory pathogen, and forming the suppository comprises forming the suppository that includes the respiratory pathogen.

[0692] Example 297. The method according to any one of examples 285-296, wherein the active ingredient includes a central nervous system (CNS) pathogen, and forming the suppository comprises forming the suppository that includes the CNS pathogen.

[0693] Example 298. The method according to any one of examples 285-297, wherein the active ingredient includes a drug, and forming the suppository comprises forming the suppository that includes the drug.

[0694] Example 299. The method according to any one of examples 285-298, wherein the active ingredient includes a biomolecule, and forming the suppository comprises forming the suppository that includes the biomolecule.

[0695] Example 300. The method according to any one of examples 285-299, wherein the active ingredient includes a vaccine, and forming the suppository comprises forming the suppository that includes the vaccine. [0696] Example 301. The method according to any one of examples 285-300, wherein the encapsulating material has a melting point of 25-37 degrees C, and forming the suppository comprises forming the suppository with the encapsulating material that has the melting point that is between 25 and 37 degrees C.

[0697] Example 302. The method according to any one of examples 285-301, wherein the encapsulating material includes glycerinated glycerin, and forming the suppository comprises forming the suppository that includes glycerinated glycerin.

[0698] Example 303. The method according to any one of examples 285-302, wherein the encapsulating material includes cocoa butter, and forming the suppository comprises forming the suppository that includes cocoa butter.

[0699] Example 304. The method according to any one of examples 285-303, wherein the encapsulating material includes a polyethylene glycol, and forming the suppository comprises forming the suppository that includes the polyethylene glycol.

[0700] Example 305. The method according to any one of examples 285-304, wherein the encapsulating material includes a hydrogel, and forming the suppository comprises forming the suppository that includes the hydrogel.

[0701] Example 306. The method according to any one of examples 285-305, wherein forming the suppository comprises adding a non-irritating excipient that has a melting point that is between 25 and 37 degrees C.

[0702] Example 307. The method according to any one of examples 285-306, wherein forming the suppository comprises forming the suppository to include the encapsulating material and the reporter dye in an outer layer, and the active ingredient in a core internal to the outer layer.

[0703] Example 308. The method according to any one of examples 285-307, wherein forming the suppository comprises forming the suppository to include the encapsulating material in a capsule layer, and the active ingredient and the reporter dye in a core internal to the capsule layer.

[0704] Example 309. The method according to any one of examples 285-308, wherein forming the suppository comprises forming the suppository to include the encapsulating material in a capsule layer, the reporter dye in a reporter dye layer that is discrete from the capsule layer, and the active ingredient in a core that is discrete from the reporter dye layer. [0705] Example 310. The method according to example 309, wherein forming the suppository comprises forming the suppository such that the reporter dye layer is internal to the capsule layer, and the core is internal to the reporter dye layer.

[0706] Example 311. A method, comprising: lining a suppository capsule with a reporter dye; and subsequently, filling the lined capsule with an active ingredient.

[0707] Example 312. The method according to example 311, wherein lining the suppository capsule with the reporter dye comprises lining the suppository capsule with the reporter dye by serial layer manufacturing.

[0708] Example 313. The method according to any one of examples 311-312, wherein the reporter dye comprises methylene blue, and lining the suppository capsule with the reporter dye comprises lining the suppository capsule with methylene blue.

[0709] Example 314. The method according to any one of examples 311-313, wherein the reporter dye comprises carmine red, and lining the suppository capsule with the reporter dye comprises lining the suppository capsule with carmine red.

[0710] Example 315. The method according to any one of examples 311-314, wherein the reporter dye comprises a turmeric extract, and lining the suppository capsule with the reporter dye comprises lining the suppository capsule with the turmeric extract.

[0711] Example 316. The method according to any one of examples 311-315, wherein the reporter dye comprises a beet extract, and lining the suppository capsule with the reporter dye comprises lining the suppository capsule with the beet extract.

[0712] Example 317. The method according to any one of examples 311-316, wherein the active ingredient comprises a SARS-CoV-2 virus, and filling the lined capsule with the active ingredient comprises filling the lined capsule with the SARS-CoV-2 virus.

[0713] Example 318. The method according to any one of examples 311-317, wherein the active ingredient comprises a respiratory pathogen, and filling the lined capsule with the active ingredient comprises filling the lined capsule with the respiratory pathogen.

[0714] Example 319. The method according to any one of examples 311-318, wherein the active ingredient comprises a central nervous system (CNS) pathogen, and filling the lined capsule with the active ingredient comprises filling the lined capsule with the CNS pathogen. [0715] Example 320. The method according to any one of examples 311-319, wherein the active ingredient comprises a drug, and filling the lined capsule with the active ingredient comprises filling the lined capsule with the drug.

[0716] Example 321. The method according to any one of examples 311-320, wherein the active ingredient comprises a biomolecule, and filling the lined capsule with the active ingredient comprises filling the lined capsule with the biomolecule.

[0717] Example 322. The method according to any one of examples 311-321, wherein the active ingredient comprises a vaccine, and filling the lined capsule with the active ingredient comprises filling the lined capsule with the vaccine.

[0718] Example 323. A method, comprising: forming an encapsulation mixture by mixing a reporter dye with a molten encapsulating material; and forming a suppository by encapsulating an active ingredient in the encapsulation mixture.

[0719] Example 324. A method, comprising: providing a dissolvable capsule; encapsulating an active ingredient as a solid insert in the dissolvable capsule to create a suppository; and injecting a reporter dye between the dissolvable capsule and the solid insert.

[0720] Example 325. A method, comprising: identifying a human subject to be immunized against a non-gastrointestinal pathogen, and responsively to the identifying, rectally infecting the subject with the non- gastrointestinal pathogen.

[0721] Example 326. The method according to example 325, wherein the human subject is a human subject infected with the non-gastrointestinal pathogen, and rectally infecting the subject is used as a means of stimulating a systemic immune response to the non- gastrointestinal pathogen.

[0722] Example 327. The method according to any one of examples 325-326, wherein the human subject is a human subject infected with the non-gastrointestinal pathogen, and rectally infecting the subject is used as a means of stimulating an immune response to the non-gastrointestinal pathogen. It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.

[0723] Example 328. A wipe, formulated for rectal application, and comprising a non- pathogenic, recombinant virus encoding an epitope of a pathogen.

[0724] Example 329. A suppository, formulated for rectal administration, and comprising a non-pathogenic, recombinant virus encoding an epitope of a pathogen .

[0725] Example 330. An enema, formulated for rectal administration, and comprising a non-pathogenic, recombinant virus encoding an epitope of a pathogen.

[0726] Example 331. A wipe, formulated for rectal application, and comprising a first virus encoding an epitope of a second virus.

[0727] Example 332. A suppository, formulated for rectal administration, and comprising a first virus encoding an epitope of a second virus.

[0728] Example 333. An enema, formulated for rectal administration, and comprising a first virus encoding an epitope of a second virus.

[0729] Example 334. The wipe according to any one of examples 1-19, wherein the respiratory virus is a recombinant virus encoding an epitope of HIV.

[0730] Example 335. The suppository according to any one of examples 20-39, wherein the respiratory virus is a recombinant virus encoding an epitope of HIV.

[0731] Example 336. The method according to any one of examples 74-90, wherein the respiratory virus is a recombinant virus comprising an epitope of HIV, and wherein inoculating the subject with the respiratory virus comprises inoculating the subject with the recombinant influenza virus comprising an epitope of HIV.

[0732] Example 337: The swab-compatible gel according to any one of claims 151-166, wherein the respiratory virus is a recombinant virus encoding an epitope of a pathogen.

[0733] Example 338: The enema formulation according to any one of claims 167-185, wherein the respiratory virus is a recombinant virus encoding an epitope of a pathogen.

Claims

1. A wipe, formulated for rectal application, and comprising a respiratory virus.

2. The wipe according to claim 1, further comprising a suspension of cells supportive of the respiratory virus.

3. The wipe according to any one of claims 1-2, wherein the wipe comprises a swabcompatible gel.

4. The wipe according to any one of claims 1-3, wherein the wipe comprises a polymeric material.

5. The wipe according to any one of claims 1-4, wherein the respiratory virus is unencapsulated.

6. The suppository according to any one of claims 1-5, wherein the respiratory virus is an RNA virus.

7. The suppository according to any one of claims 1-6, wherein the respiratory virus is an influenza virus.

8. The suppository according to any one of claims 1-6, wherein the respiratory virus is a coronavirus.

9. The wipe according to claim 8, wherein the respiratory virus is SARS-CoV-2.

10. The wipe according to any one of claims 1-6, wherein the respiratory virus is a recombinant virus that encodes an epitope of a pathogen.

11. The suppository according to claim 10, wherein the respiratory virus is a recombinant influenza virus that encodes an epitope of HIV.

12. The wipe according to any one of claims 1-9, wherein the respiratory virus is live.

13. The wipe according to any one of claims 1-12, wherein the respiratory virus is heat inactivated.

14. The wipe according to any one of claims 1-13, wherein the respiratory virus is heatsensitive.

15. The wipe according to any one of claims 1-14, wherein the respiratory virus is chemically inactivated.

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16. The wipe according to any one of claims 1-15, wherein the wipe is maintained in a frozen state until administration.

17. The wipe according to any one of claims 1-16, wherein the respiratory virus is attenuated.

18. The wipe according to any one of claims 1-17, further comprising lyophilization stabilizers.

19. The wipe according to any one of claims 1-18, further comprising penetrants.

20. The wipe according to any one of claims 1-19, wherein the wipe comprises the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

21. The wipe according to claim 20, wherein the wipe comprises the respiratory virus at approximately lxlO^A4 PFU per dose.

22. A suppository, formulated for rectal administration, and comprising a respiratory virus.

23. The suppository according to claim 22, further comprising a suspension of cells supportive of the respiratory virus.

24. The suppository according to any one of claims 22-23, wherein the respiratory virus is selected from the group consisting of: a rhinovirus, an adenovirus, a respiratory syncytial virus (RSV), a parainfluenza virus, a metapneumovirus, and an influenza virus.

25. The suppository according to any one of claims 22-24, wherein the suppository comprises a layered capsule.

26. The suppository according to any one of claims 22-25, wherein the respiratory virus is unencapsulated.

27. The suppository according to any one of claims 22-26, wherein the respiratory virus is an RNA virus.

28. The suppository according to any one of claims 22-27, wherein the respiratory virus is an influenza virus.

29. The suppository according to any one of claims 22-27, wherein the respiratory virus is a coronavirus.

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30. The suppository according to claim 29, wherein the coronavirus virus is SARS-CoV-

2.

31. The suppository according to any one of claims 22-27, wherein the respiratory virus is a recombinant virus that encodes an epitope of a pathogen.

32. The suppository according to claim 31, wherein the respiratory virus is a recombinant influenza virus that encodes an epitope of HIV.

33. The suppository according to any one of claims 22-30, wherein the respiratory virus is live.

34. The suppository according to any one of claims 22-33, wherein the respiratory virus is heat inactivated.

35. The suppository according to any one of claims 22-34, wherein the respiratory virus is heat-sensitive.

36. The suppository according to any one of claims 22-35, wherein the respiratory virus is chemically inactivated.

37. The suppository according to any one of claims 22-36, wherein the suppository is maintained in a frozen state until administration.

38. The suppository according to any one of claims 22-37, wherein the respiratory virus is attenuated.

39. The suppository according to any one of claims 22-38, further comprising lyophilization stabilizers.

40. The suppository according to any one of claims 22-39, further comprising penetrants.

41. The suppository according to any one of claims 22-40, further comprising a high molecular weight glycoprotein.

42. The suppository according to any one of claims 22-41, wherein the suppository comprises the respiratory virus at approximately lxlO^A2 to lxl0^A10 PFU per dose.

43. The suppository according to claim 42, wherein the suppository comprises the respiratory virus at approximately lxlO^A4 PFU per dose.

44. A wipe, formulated for mucosal application, and comprising a non-pathogenic, recombinant virus encoding an epitope of a pathogen.

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45. A suppository, formulated for mucosal administration, and comprising a non- pathogenic, recombinant virus encoding an epitope of a pathogen.

46. A wipe, formulated for mucosal application, and comprising a first virus encoding an epitope of a second virus.

47. A suppository, formulated for mucosal administration, and comprising a first virus encoding an epitope of a second virus.

48. A method, comprising: identifying a human subject to be immunized against HIV; and, responsively to the identifying, rectally administering, to the subject, a formulation comprising a recombinant influenza virus that encodes an epitope of HIV.

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