WO2022204017A1 - Évaluations d'immunisation à l'aide d'un échantillon salivaire ou nasal - Google Patents

Évaluations d'immunisation à l'aide d'un échantillon salivaire ou nasal Download PDF

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WO2022204017A1
WO2022204017A1 PCT/US2022/021129 US2022021129W WO2022204017A1 WO 2022204017 A1 WO2022204017 A1 WO 2022204017A1 US 2022021129 W US2022021129 W US 2022021129W WO 2022204017 A1 WO2022204017 A1 WO 2022204017A1
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vaccine
antibody
binds
antigen
derived
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PCT/US2022/021129
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English (en)
Inventor
Vladimir I. Slepnev
Albina IBRAYEVA
Aubree MADES
Lauren LOPEZ
Prithivi CHELLAMUTHU
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Curative Inc.
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Publication of WO2022204017A1 publication Critical patent/WO2022204017A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase

Definitions

  • the present disclosure is directed to methods comprising the determination of a level of an antibody in an oral or nasal sample, such as for assessing an antibody profile or vaccine immunogenicity. Also provided in other aspects of the disclosure are kits and compositions useful for the methods described herein.
  • the present application provides, in some aspects, methods of determining an antibody profile in a composition comprising a saliva or nasal sample from an individual, wherein the saliva or nasal sample is collected from the individual following administration of a vaccine against a disease, such as a cancer or a disease caused by an infectious agent.
  • a method of assessing vaccine immunogenicity in an individual following administration of a vaccine against an infectious agent comprising: (a) determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva sample from the individual; and (b) comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • the saliva sample is collected by the individual.
  • the composition comprising the saliva sample comprises a reagent.
  • a method of assessing vaccine immunogenicity in an individual following administration of a vaccine against an infectious agent comprising: determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a nasal sample from the individual, wherein the individual displays vaccine immunogenicity if the antibody that binds to the antigen of, or derived from, the vaccine is present.
  • the method further comprises comprising comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • the nasal sample is collected by the individual. In some embodiments, the nasal sample is collected using a nasal swab. In some embodiments, the composition comprising the nasal sample comprises a reagent.
  • the saliva or nasal sample from the individual is obtained at least about 3 days following administration of the vaccine. In some embodiments, the saliva or nasal sample from the individual is obtained at least about 10 days following administration of the vaccine. In some embodiments, the saliva or nasal sample from the individual is obtained at 15 days following administration of the vaccine.
  • the administration of the vaccine is the first administration of the vaccine to the individual. In some embodiments, the administration of the vaccine is the second administration of the vaccine to the individual.
  • the level of the reference antibody that binds the antigen of, or derived from, the infectious agent is the median or mean level of the reference antibody determined from the population of patients infected with the infectious agent, and wherein the population of patients is at least about 10 patients. In some embodiments, each patient of the population of patients has been infected with the infectious agent within about 1 year of determining a level of the reference antibody.
  • the population of patients infected with the infectious agent suffered a disease associated with the infectious agent.
  • the antigen of, or derived from, the vaccine and the antigen of, or derived from, the infectious agent are the same.
  • the vaccine is an mRNA vaccine.
  • the isotype of the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent is selected from the group consisting of IgG, IgA, and IgM, or a combination thereof.
  • the isotype of the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent is the same.
  • the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent are IgG.
  • the infectious agent is a virus.
  • the virus is of the Coronaviridae family.
  • the virus is of the Betacoronavirus genus.
  • the virus is of the Sarbecovirus subgenus.
  • the virus is of the SARSr-CoV species.
  • the virus is a SARS-CoV strain.
  • the vims is selected from the group consisting of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Bat SARS-like coronavirus WIV1 (Bat SL-CoV-WIVl), alpha coronaviruses 229E (HCoV-229E), New Haven coronavirus NL63 (HCoV-NL63), beta coronaviruses OC43 (HCoV-OC43), coronavirus HKU 1 (HCoV-HKU 1 ), and Middle East Respiratory Syndrome coronavirus (MERS-CoV).
  • SARS-CoV-2 Severe Acute Respiratory Syndrome coronavirus 2
  • SARS-CoV Severe Acute Respiratory Syndrome coronavirus
  • Bat SARS-like coronavirus WIV1 Bat SL-CoV-WIVl
  • alpha coronaviruses 229E HcoV-229E
  • the antibody that binds to the antigen of, or derived from, the vaccine binds to a nucleocapsid of the vims.
  • the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a nucleocapsid of the vims.
  • the antibody that binds to the antigen of, or derived from, the vaccine binds to a spike protein of the vims.
  • the antibody that binds to the antigen of, or derived from, the vaccine binds to a SI domain of the spike protein of the vims.
  • the antibody that binds to the antigen of, or derived from, the vaccine binds to a S2 domain of the spike protein of the vims.
  • the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a spike protein of the vims.
  • the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a SI domain of the spike protein of the vims.
  • the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a S2 domain of the spike protein of the vims.
  • determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises measuring the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine in the composition comprising the saliva sample.
  • determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises measuring the concentration of the antibody that binds to the antigen of, or derived from, the vaccine in the composition comprising the saliva sample.
  • the method further comprises determining the level of the antibody that binds to the antigen of, or derived from, the vaccine in a saliva sample from the individual acquired from the individual at least 3 months after administration of the vaccine. [0024] In some embodiments, the method further comprises obtaining the saliva or nasal sample. In some embodiments, the method further comprises admixing the saliva or nasal sample with a reagent.
  • the method further comprises a sample processing step.
  • determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises an enzyme-linked immunosorbent assay (ELISA) technique.
  • the ELISA technique is a quantitative ELISA technique.
  • the infectious agent causes a disease.
  • the disease is Coronavirus Disease-2019 (COVID-19), an Angiotensin-Converting Enzyme 2 (ACE2)-associated disease, Acute Respiratory Distress Syndrome (ARDS), Severe Acute Respiratory Syndrome (SARS), or Middle East respiratory syndrome (MERS).
  • ACE2 Angiotensin-Converting Enzyme 2
  • ARDS Acute Respiratory Distress Syndrome
  • SARS Severe Acute Respiratory Syndrome
  • MERS Middle East respiratory syndrome
  • a method of determining an antibody profile in a composition comprising a saliva or nasal sample from an individual, wherein the saliva or nasal sample is collected from the individual following administration of a vaccine against an infectious agent comprising determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising the saliva or nasal sample from the individual, wherein the antibody profile is based on the level of the antibody that binds to the antigen of, or derived from, the vaccine.
  • the antibody profile comprises the presence or absence of the antigen of, or derived from, the vaccine.
  • the antibody profile comprises the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine.
  • the antibody profile comprises the quantity of the antibody that binds to the antigen of, or derived from, the vaccine.
  • the method further comprises comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent.
  • a method of assessing vaccine immunogenicity in an individual following administration of a vaccine against a disease comprising: (a) determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva or a nasal sample from the individual; and (b) comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • a method of determining an antibody profile in a composition comprising a saliva or nasal sample from an individual, wherein the saliva or nasal sample is collected from the individual following administration of a vaccine against a disease comprising determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising the saliva or nasal sample from the individual, wherein the antibody profile is based on the level of the antibody that binds to the antigen of, or derived from, the vaccine.
  • the disease is a cancer.
  • the antigen is a polypeptide.
  • the antigen is a polypeptide present in or on the surface of a cancer cell.
  • the vaccine is an mRNA vaccine.
  • FIG. 2 shows a plot of the detection of IgG antibodies against SARS-CoV-2 from saliva samples in the days following vaccination by a first Moderna vaccine dose in individuals previously infected by the virus. Positive antibody signal was detected in all individuals 20 days post vaccination based on a positive cutoff of 0.2 absorbance units (a.u.).
  • the present application provides, in some aspects, methods of determining an antibody profile in a composition comprising a saliva or nasal sample from an individual, wherein the saliva or nasal sample is collected from the individual following administration of a vaccine against a disease, such as a cancer or a disease caused by an infectious agent.
  • the method comprises assessing vaccine immunogenicity in the individual following administration of the vaccine against the disease.
  • the present application is based, at least in part, on the inventors’ findings that antibodies that bind an antigen of, or derived from, a vaccine can be measured in oral and/or nasal specimens obtained following administration of the vaccine, and that such measurements can be used to assess the status of an individual, e.g ., based on vaccine immunogenicity or the need for initial and/or further vaccination.
  • a critical need for rapid, reliable, non-invasive, and safe testing procedures to, e.g. , evaluate immunization status, such as SARS-Cov-2 immunization status, of an individual.
  • immunization status such as SARS-Cov-2 immunization status
  • mRNA vaccines have demonstrated strong protection against COVID-19 disease caused by the SARS CoV-2 virus.
  • the mRNA vaccines require two injections within a relatively short period of time (about 3 weeks apart).
  • the need for multiple injections during a time of vaccine shortage presents a difficult choice in vaccine distribution.
  • should available vaccines be used by administering a single dose to maximal number of patients or by administering both injections to a smaller population thereby extending epidemics for at least twice as long.
  • some individuals are protective immunity after a single vaccination and others do not. Assessing effectiveness of vaccination at the population scale would provide an optimal approach to balance broad application without compromising efficiency of vaccination.
  • serological methods are needed to assess response to a vaccination. Common serological methods are slow, expensive, and inconvenient to be applied at a large scale, such as for hundreds of millions of patients.
  • the disclosure provided herein enables an alternative approach based on measuring one or more antibodies to a viral antigen (such as of, or derived from, a vaccine) using self- collected saliva or nasal specimen.
  • the disclosure provided herein presents a rapid, reliable, non-invasive, and safe testing procedure to, e.g, evaluate immunization status, such as SARS- Cov-2 immunization status, of an individual in a manner that can be completed rapidly on a mass scale.
  • a level of detected antibodies in a saliva or nasal sample from an individual following administration of a vaccine (such as at least about two weeks after administration) at or higher than a median (or average) level of antibodies in patients infected with SARS CoV-2 virus indicates protection against COVID-19 disease.
  • Such information can then be utilized to characterize a patient, such as not needing additional vaccination, needing additional vaccination, or having protective immunity.
  • the disclosure provided herein is broadly applicable to vaccines targeting a disease.
  • the methods described herein are useful evaluating a patient response to a vaccine, including an mRNA vaccine, against a cancer.
  • the methods described herein are useful for assessing for a level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva or a nasal sample from the individual.
  • antibody testing could be conducted using nasal swab specimens.
  • Advantages of nasal swab collection comprise non-invasive self-collection which does not require the participation of health care professional, faster collection speed, and comparing to saliva specimen collection, doesn’t require restrictions of food or drinking prior to sample collection.
  • Specimen collection from upper respiratory organs is particularly useful for determining immune response to respiratory pathogens, as the presence of antibody at the primary site of infection should provide protection against said respiratory pathogens.
  • polypeptide and “protein,” as used herein, may be used interchangeably to refer to a polymer comprising amino acid residues, and are not limited to a minimum length. Such polymers may contain natural or non-natural amino acid residues, or combinations thereof, and include, but are not limited to, peptides, polypeptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. Full-length polypeptides or proteins, and fragments thereof, are encompassed by this definition. The terms also include modified species thereof, e.g ., post- translational modifications of one or more residues, for example, methylation, phosphorylation glycosylation, sialylation, or acetylation.
  • antibody includes full-length antibodies and antigen-binding fragments thereof.
  • a full-length antibody comprises two heavy chains and two light chains.
  • the variable regions of the light and heavy chains are responsible for antigen binding.
  • the variable region in both chains generally contain three highly variable loops called the complementarity determining regions (CDRs) (light chain (LC) CDRs including LC-CDR1, LC-CDR2, and LC- CDR3, heavy chain (HC) CDRs including HC-CDR1, HC-CDR2, and HC-CDR3).
  • CDRs complementarity determining regions
  • CDR boundaries for the antibodies and antigen-binding fragments disclosed herein may be defined or identified by the conventions of Rabat, Chothia, or Al-Lazikani (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Rabat 1987; Rabat 1991).
  • the three CDRs of the heavy or light chains are interposed between flanking stretches known as framework regions (FRs), which are more highly conserved than the CDRs and form a scaffold to support the hypervariable loops.
  • FRs framework regions
  • the constant regions of the heavy and light chains are not involved in antigen binding, but exhibit various effector functions.
  • Antibodies are assigned to classes based on the amino acid sequence of the constant region of their heavy chain.
  • the five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, which are characterized by the presence of a, d, e, g, and m heavy chains, respectively.
  • Several of the major antibody classes are divided into subclasses such as lgGl (g ⁇ heavy chain), lgG2 ( j 2 heavy chain), lgG3 (g3 heavy chain), lgG4 (g4 heavy chain), IgAl (al heavy chain), or lgA2 (a2 heavy chain).
  • antigen-binding fragment refers to an antibody fragment including, for example, a diabody, a Fab, a Fab', a F(ab')2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv 1 ), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), an scFv dimer (bivalent diabody), a multispecific antibody formed from a portion of an antibody comprising one or more CDRs, a camelized single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, or any other antibody fragment that binds to an antigen but does not comprise a complete antibody structure.
  • an antigen-binding fragment is capable of binding to the same antigen to which the parent antibody or a parent antibody fragment (e.g ., a parent scFv) binds.
  • an antigen-binding fragment may comprise one or more CDRs from a particular human antibody grafted to a framework region from one or more different human antibodies.
  • epitope refers to the specific group of atoms or amino acids on an antigen to which an antibody binds. Two antibodies may bind the same epitope within an antigen if they exhibit competitive binding for the antigen.
  • the term “specifically binds” or “specific for” refers to measurable and reproducible interactions, such as binding between a target and an antibody that is determinative of the presence of the target in the presence of a heterogeneous population of molecules, including biological molecules.
  • an antibody that specifically binds to a target (which can be an epitope) is an antibody that binds this target with greater affinity, avidity, more readily, and/or with greater duration than its bindings to other targets.
  • an antibody that specifically binds to an antigen reacts with one or more antigenic determinants of the antigen with a binding affinity that is at least about 10 times its binding affinity for other targets.
  • CDR complementarity determining region
  • CDR complementarity determining region
  • Rabat etal. J. Biol. Chem. 252:6609-6616 (1977); Rabat et al., U.S. Dept of Health and Human Services, “Sequences of proteins of immunological interest” (1991); by Chothia etal. , J. Mol. Biol. 196:901-917 (1987); and MacCallum etal., J. Mol. Biol. 262:732-745 (1996), where the definitions include overlapping or subsets of amino acid residues when compared against each other.
  • an FcR of this invention is one that binds an IgG antibody (a g receptor) and includes receptors of the FcyRI, FcyRII, and FcyRIII subclasses, including allelic variants and alternatively spliced forms of these receptors.
  • FcyRII receptors include FcyRIIA (an “activating receptor”) and FcyRIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof.
  • Activating receptor FcyRIIA contains an immunoreceptor tyrosine-based activation motif (IT AM) in its cytoplasmic domain.
  • Inhibiting receptor FcyRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (see review M. in Daeron, Annu. Rev. Immunol. 15:203-234 (1997)).
  • the term includes allotypes, such as FcyRIIIA allotypes: Fc/yRTTTA-Phel 58 Fc Y RHlA-Val l 5 Fc Y RIIA-R131 and/or Fc Y RIIA-H131.
  • FcRs are reviewed in Ravetch and Kinet, Annu. Rev.
  • FcR neonatal receptor
  • a “functional Fc fragment” possesses an “effector function” of a native sequence Fc region.
  • effector functions include Clq binding; complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g. B cell receptor; BCR), etc.
  • Such effector functions generally require the Fc region to be combined with a binding domain (e.g. an antibody variable domain) and can be assessed using various assays known in the art.
  • the term “individual” refers to a mammal and includes, but is not limited to, human, bovine, horse, feline, canine, rodent, or primate.
  • Reference to “about” a value or parameter herein includes (and describes) variations that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X.”
  • sample such as a saliva sample or a nasal sample
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • the sample is obtained following administration of a vaccine, such as a pre-determined number of days following administration of the vaccine.
  • the method comprises the determination of a level of an antibody that binds to an antigen of, or derived from, a vaccine in a composition comprising a saliva or nasal sample from an individual following administration of the vaccine.
  • a method of determining an antibody profile in a composition comprising a saliva or nasal sample from an individual, wherein the saliva or nasal sample is collected from the individual following administration of a vaccine against a disease comprising determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising the saliva or nasal sample from the individual, wherein the antibody profile is based on the level of the antibody that binds to the antigen of, or derived from, the vaccine.
  • the antibody profile comprises a comparison against a reference antibody level.
  • the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the disease determined from a population of patients having the disease.
  • the disease is a cancer.
  • the disease is caused by, or a result of, an infection by an infectious agent.
  • the infectious agent is a virus.
  • a method of assessing vaccine immunogenicity in an individual following administration of a vaccine against a disease comprising determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva or nasal sample from the individual.
  • the method further comprises comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the disease determined from a population of patients having the disease.
  • the disease is a cancer.
  • the disease is caused by, or a result of, an infection by an infectious agent.
  • the infectious agent is a virus.
  • a method of assessing vaccine immunogenicity in an individual following administration of a vaccine against an infectious agent comprising: (a) determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva or nasal sample from the individual; and (b) comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • the infectious agent is a virus.
  • a method of assessing vaccine immunogenicity in an individual following administration of a vaccine against an infectious agent comprising: (a) determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva or nasal sample from the individual; and (b) comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the an infectious agent (such as a SARS-CoV virus, for example, SARS-CoV-2 virus, or a variant thereof) determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the infectious agent (such as a SARS-CoV virus, for example, SARS-CoV-2 virus, or a variant thereof) determined from a population of patients infected with the infectious
  • the antibody and/or the reference antibody bind to a nucleocapsid of the infectious agent (such as a SARS-CoV virus, for example, SARS-CoV-2 virus, or a variant thereof).
  • the antibody and/or the reference antibody bind to a spike protein of the infectious agent (such as a SARS- CoV virus, for example, SARS-CoV-2 virus, or a variant thereof).
  • the antibody and/or the reference antibody bind to a SI domain of the spike protein of the SARS- CoV virus (such as a SARS-CoV-2 virus, or a variant thereof).
  • the antibody and/or the reference antibody bind to a S2 domain of the spike protein of the SARS- CoV virus (such as a SARS-CoV-2 virus, or a variant thereof).
  • a method of assessing vaccine immunogenicity in an individual following administration of a vaccine against a cancer comprising: (a) determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva or nasal sample from the individual; and (b) comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the cancer determined from a population of patients infected with the cancer, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • the methods provided herein are applicable to variety of diseases and infectious agents thereof.
  • the methods may be used to analyze the disease and/or infectious agent in a sample, such as a saliva sample and/or a nasal sample.
  • the infectious agent is a virus.
  • the virus is of the Coronaviridae family.
  • the virus is of the Betacoronavirus genus.
  • the virus is of the Sarbecovirus subgenus.
  • the virus is of the SARSr-CoV species.
  • the virus is a SARS-CoV strain.
  • the virus is a Severe Acute Respiratory Syndrome coronavirus 2 (SARS- CoV-2), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Bat SARS-like coronavirus WIV1 (Bat SL-CoV-WIVl), alpha coronaviruses 229E (HCoV-229E), New Haven coronavirus NL63 (HCoV-NL63), beta coronaviruses OC43 (HCoV-OC43), coronavirus HKU1 (HCoV-HKUl), or Middle East Respiratory Syndrome coronavirus (MERS-CoV).
  • SARS- CoV-2 Severe Acute Respiratory Syndrome coronavirus 2
  • SARS-CoV Severe Acute Respiratory Syndrome coronavirus
  • Bat SARS-like coronavirus WIV1 Bat SL-CoV-WIVl
  • alpha coronaviruses 229E HcoV-229E
  • the virus is a SARS-CoV-2 virus.
  • the virus is a SARS-CoV-2 variant.
  • Exemplary SARS-CoV-2 variants and spike protein mutations associated with these variants are shown in Table A below.
  • the SARS-COV-2 variants described herein are named by the World Health Organization or according to the Phylogenetic Assignment of Named Global Outbreak (PANGO) Lineages software. It is understood that the same variants may be referred to using different naming systems and algorithms in the art.
  • the SARS-CoV-2 variant is selected from the group consisting of an Alpha (i.e., B.l.1.7 and Q) variant, a Beta (i.e., B.1.351) variant, a Gamma (i.e., P.1, also known as B.1.1.28.1) variant, an Epsilon (i.e., B.1.427 or B.1.429) variant, an Eta (i.e.,
  • B.1.525 an Iota (i.e., B.1.526) variant, a Kappa (i.e., B.1.617.1) variant, a B. 1.617.3 variant, a Zeta (z.e., P.2) variant, a Mu (i.e., B 1 621 or B.1.621.1) variant, aDelta (i.e.,
  • the SARS-CoV-2 variant is a Delta variant, such as a B.1.617.2 variant, or an AY variant.
  • the SARS-CoV-2 variant is an Omicron variant, such as a B.1.529 variant or a BA variant.
  • the SARS-CoV-2 variant has one or more mutations (e.g., insertion, deletion, and/or substitution) in the spike protein.
  • the one or more mutations in the spike protein may affect viral fitness, such as transmissibility, virulence, and/or drug resistance (e.g, resistance to neutralizing antibodies and/or resistance to a vaccine). In some embodiments, the one or more mutations in the spike protein do not substantially alter viral fitness. In some embodiments, the SARS-CoV-2 variant does not have a mutation in the spike protein
  • the infectious agent causes a disease.
  • the disease is Coronavirus Disease-2019 (COVID-19), an Angiotensin-Converting Enzyme 2 (ACE2)-associated disease, Acute Respiratory Distress Syndrome (ARDS), Severe Acute Respiratory Syndrome (SARS), or Middle East respiratory syndrome (MERS).
  • ACE2 Angiotensin-Converting Enzyme 2
  • ARDS Acute Respiratory Distress Syndrome
  • SARS Severe Acute Respiratory Syndrome
  • MERS Middle East respiratory syndrome
  • the disease is a variant of COVID-19, an ACE2-assoicated disease, ARDS,
  • the methods comprise administering a vaccine against the disease or infectious agent.
  • the antigen of, or derived from the infectious agent may be bound by an antibody.
  • the antibody that binds to the antigen of, or derived from, the vaccine binds to a nucleocapsid of the infectious agent (e.g., a virus).
  • the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a nucleocapsid of the virus.
  • the antibody and the reference antibody both bind to a nucleocapsid of the virus.
  • the nucleocapsid comprises a spike protein.
  • the antibody that binds to the antigen of, or derived from, the vaccine binds to a spike protein of the virus.
  • the antibody that binds to the antigen of, or derived from, the vaccine binds to a SI domain of the spike protein of the virus.
  • the antibody that binds to the antigen of, or derived from, the vaccine binds to a S2 domain of the spike protein of the virus.
  • the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a spike protein of the virus.
  • the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a SI domain of the spike protein of the virus. In some embodiments, the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a S2 domain of the spike protein of the virus.
  • the antibody and the reference antibody bind to different domains of the spike protein of the virus.
  • the antibody binds to a SI domain of the spike protein of the virus, and the reference antibody binds to a S2 domain of the spike protein of the virus.
  • the antibody binds to a S2 domain of the spike protein of the virus, and the reference antibody binds to a SI domain of the spike protein of the virus.
  • the antibody and the reference antibody bind to the same domain of the spike protein of the virus. In some embodiments, the antibody and the reference antibody both bind to a SI domain of the spike protein of the virus. In some embodiments, the antibody and the reference antibody both bind to a S2 domain of the spike protein of the virus.
  • the disease is a cancer.
  • the antigen of, or derived from the cancer may be bound by an antibody.
  • the antigen is a polypeptide. In some embodiments, the antigen is a polypeptide present in or on the surface of a cancer cell.
  • the method comprises administering a vaccine against an infectious agent to an individual, such as any of the infectious agents described herein.
  • the vaccine is vaccine against COVID-19 (i.e., an mRNA vaccine against SARS- CoV-2) or a variant thereof, a vaccine against ACE2-associated disease vaccine or a variant thereof, a vaccine against ARDS or a variant thereof, a vaccine against SARS or a variant thereof, or a vaccine against MERS or a variant thereof.
  • the vaccine is a vaccine against COVID-19 (i.e., a vaccine against SARS-CoV-2), or a variant thereof.
  • the vaccine is vaccine against cancer.
  • the administration of the vaccine is the first administration of the vaccine to the individual. In some embodiments, the administration of the vaccine is the second administration of the vaccine to the individual. In some embodiments, the administration of the vaccine is the third, or greater, administration of the vaccine to the individual.
  • the vaccine is an inactivated virus vaccine, a live-attenuated virus vaccine, a subunit, recombinant, polysaccharide, or conjugate vaccine, a toxoid vaccine, a viral vector vaccine, or a messenger RNA (mRNA) vaccine.
  • the vaccine is an mRNA vaccine against COVID-19 (i.e., an mRNA vaccine against SARS-CoV-2) or a variant thereof, an mRNA vaccine against ACE2-associated disease vaccine or a variant thereof, an mRNA vaccine against ARDS or a variant thereof, an mRNA vaccine against SARS or a variant thereof, or an mRNA vaccine against MERS or a variant thereof.
  • the vaccine is an mRNA vaccine against COVID-19 (i.e., an mRNA vaccine against SARS- CoV-2), or a variant thereof.
  • the vaccine is an mRNA vaccine against cancer.
  • the antigen of, or derived from, the vaccine and the antigen of, or derived from, the infectious agent are the same.
  • the vaccine and the antigen of, or derived from, the infectious agent may both be derived from COVID-19 (i.e., SARS-CoV-2) or a variant thereof, an ACE2-associated disease or a variant thereof, ARDS or a variant thereof, SARS or a variant thereof, or MERS or a variant thereof.
  • the vaccine and the antigen of, or derived from, the infectious agent are both derived from COVID-19 (i.e., SARS-CoV-2).
  • the vaccine is an mRNA vaccine, and the mRNA vaccine and the antigen of, or derived from, the infectious agent are both derived from COVID-19 (i.e., SARS-CoV-2).
  • the antigen of, or derived from, the vaccine and the antigen of, or derived from, the disease are the same.
  • the vaccine and the antigen of, or derived from, the disease are both derived from a polypeptide present on a cancer cell.
  • the vaccine is an mRNA vaccine, and the mRNA vaccine and the antigen of, or derived from, the disease are both derived from a polypeptide present on a cancer cell.
  • the isotype of the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent is the same.
  • the isotype is IgG, IgM, or IgA. In some embodiments, the isotype is IgG.
  • the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent are IgG, IgM, or IgA. In some embodiments, the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent are IgG.
  • the sample is a biological sample.
  • the sample is a biological sample comprising a biological material.
  • the biological material is selected from the group consisting of a nucleic acid and a polypeptide.
  • the nucleic acid is an RNA or a DNA.
  • the sample comprises a bodily fluid, such as a sample comprising a saliva sample, a nasal sample, blood sample, serum sample, convalescent plasma sample, oropharyngeal sample, including that obtained from an oropharyngeal swab, nasopharyngeal sample, including that obtained from a nasal swab (e.g., a nasopharyngeal swab), an oral swab, a buccal sample, bronchoalveolar lavage sample, including that obtained from an endotracheal aspirator, a urine sample, a sweat sample, a sputum sample, a saliva sample, a tear sample, a nasal sample, a bodily excretion sample, or cerebrospinal fluid sample.
  • a bodily fluid such as a sample comprising a saliva sample, a nasal sample, blood sample, serum sample, convalescent plasma sample, oropharyngeal sample, including that obtained from an oropharyngeal
  • the biological sample is of, or derived from, an individual, such as a human.
  • the individual is a mammal, such as a human, bovine, horse, feline, canine, rodent, or primate.
  • the method comprises obtaining the sample from an individual.
  • the sample is collected by the individual.
  • the sample is collected by the same individual from which the sample is of, or derived from.
  • the sample is collected by a different individual from which the sample is of, or derived from.
  • the sample comprises a reagent.
  • reagents may be used for sample collection and downstream analysis.
  • the reagent is capable of stabilizing the sample.
  • the reagent is capable of eluting material from a sample collection tool, such as a swab.
  • the reagent is capable of determining the level of an antibody, such as for use in an enzyme-linked immunosorbent assay (ELISA) technique.
  • the sample comprises one reagent.
  • the sample comprises more than one reagent, such as a combination of reagents that may be used, for example, to stabilize the sample, to elute material from the sample collection tool, and/or to determine the level of an antibody (e.g., a reagent for use in an ELISA technique).
  • a combination of reagents that may be used, for example, to stabilize the sample, to elute material from the sample collection tool, and/or to determine the level of an antibody (e.g., a reagent for use in an ELISA technique).
  • an antibody e.g., a reagent for use in an ELISA technique
  • the sample is a saliva sample.
  • the saliva sample is collected by an individual.
  • the saliva sample is collected by the same individual from which the sample is of, or derived from.
  • the saliva sample is collected by a different individual from which the sample is of, or derived from.
  • the saliva is collected using an oral swab.
  • the composition comprising the saliva sample comprises a reagent, such as any of the reagents described herein.
  • the sample is a nasal sample.
  • the nasal sample is collected by an individual.
  • the nasal sample is collected by the same individual from which the sample is of, or derived from.
  • the nasal sample is collected by a different individual from which the sample is of, or derived from.
  • the nasal sample is collected using a nasal swab.
  • the composition comprising the nasal sample comprises a reagent, such as any of the reagents described herein.
  • the sample (e.g., a saliva or nasal sample) from the individual is obtained following administration of a vaccine, such as any of the vaccines described herein.
  • a vaccine such as any of the vaccines described herein.
  • the sample from the individual is obtained between about 1 day and about 30 days following administration of the vaccine, such as between any of about 1 day and about 5 days, about 2 days and about 12 days, about 5 days and about 18 days, about 8 days and about 20 days, and about 12 days and about 30 days, following administration of the vaccine.
  • the sample from the individual is obtained less than about 30 days following administration of the vaccine, such as less than any of about 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 days, or fewer, following administration of the vaccine. In some embodiments, the sample from the individual is obtained at least about 1 day following administration of the vaccine, such as at least any of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,
  • the sample (e.g., a saliva or nasal sample) from the individual is obtained at least about 3 days following administration of the vaccine. In some embodiments, the sample (e.g., a saliva or nasal sample) from the individual is obtained at least about 10 days following administration of the vaccine. In some embodiments, the sample (e.g., a saliva or nasal sample) from the individual is obtained at 15 days following administration of the vaccine.
  • the method further comprises obtaining the sample (e.g., a saliva or nasal sample).
  • Obtaining the sample may comprise, for example, obtaining a saliva swab or a nasal swab from the individual.
  • the method further comprises admixing the sample (e.g., a saliva or nasal sample) with a reagent, such as any of the reagents described herein.
  • the method further comprises a sample processing step.
  • the sample processing step allows for analysis of the sample.
  • the sample processing comprises stabilizing the sample.
  • the sample processing comprises eluting material from a sample collection tool.
  • the sample processing comprises determining the level of an antibody (e.g., detecting and/or quantifying an antibody) in the sample, such as via use of an ELISA technique.
  • the method comprises determining the level of an antibody that binds to an antigen of, or derived from, a vaccine.
  • determining the level of the antibody comprises measuring the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine in a composition comprising a sample, such as any of the samples described herein.
  • the sample is a saliva sample.
  • determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises measuring the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine in the composition comprising the saliva sample.
  • determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises measuring the concentration of the antibody that binds to the antigen of, or derived from, the vaccine in the composition comprising the saliva sample.
  • the sample is a nasal sample.
  • determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises measuring the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine in the composition comprising the nasal sample.
  • determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises measuring the concentration of the antibody that binds to the antigen of, or derived from, the vaccine in the composition comprising the nasal sample.
  • the method further comprises determining the level of the antibody that binds to the antigen of, or derived from, the vaccine in a sample from an individual acquired from the individual after administration of the vaccine.
  • the sample from the individual is acquired from the individual between about 1 month and about 12 months after administration of the vaccine, such as between any of about 1 month and about 6 months, about 2 months and about 8 months, and about 6 months and about 12 months, after administration of the vaccine.
  • the sample from the individual is acquired from the individual less than about 12 months after administration of the vaccine, such as less than any of about 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1.5, 1, or fewer months, after administration of the vaccine.
  • the sample from the individual is acquired from the individual at least about 1 month after administration of the vaccine, such as at least any of about 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more months after administration of the vaccine.
  • the method further comprises determining the level of the antibody that binds to the antigen of, or derived from, the vaccine in a sample from the individual acquired from the individual at least 3 months after administration of the vaccine.
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises performing a technique that detects and/or quantifies peptides, proteins, and/or antibodies.
  • the technique detects the antibody that binds to the antigen of, or derived from, the vaccine.
  • the technique quantifies the antibody that binds to the antigen of, or derived from, the vaccine.
  • the technique detects and quantifies the antibody that binds to the antigen of, or derived from, the vaccine.
  • the technique is an ELISA technique, an enzyme-linked immunospot (EPISPOT) technique, an immunoblotting technique (i.e., western blotting), an immunohistochemistry technique, an immunocytochemistry technique, a flow cytometry and fluorescence-activated cell sorting (FACS) technique, or any combination thereof.
  • EPISPOT enzyme-linked immunospot
  • FACS fluorescence-activated cell sorting
  • the technique an ELISA technique. In some embodiments, the ELISA technique is a quantitative ELISA technique.
  • the methods provided herein may comprise use of a reference antibody.
  • the reference antibody binds an antigen of, or derived from, an infectious agent determined from a population of patients infected with the infectious agent. Additional descriptions of suitable reference antibodies and diseases and infectious agents are provided herein.
  • the method comprises comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • level of the antibody that binds the antigen of, or derived from, the vaccine is equal to the reference antibody level. In some embodiments, the level of the antibody that binds the antigen of, or derived from, the vaccine is greater than the reference antibody level. In some embodiments, the level of the antibody that binds the antigen of, or derived from, the vaccine is between about 1.5 times and about 10 times greater than the reference antibody level, such as between about 1.5 times and about 4 times, about 2.5 times and about 5 times, and about 5 times and about 10 times, greater than the reference antibody level.
  • the level of the antibody that binds the antigen of, or derived from, the vaccine is less than about 10 times greater than the reference antibody level, such as about any of 9 times, 8 times, 7 times, 6, times, 5 times, 4.5 times, 4 times, 3.5 times, 3 times, 2.5 times, 2 times, 1.5 times, or fewer, greater than the reference antibody level. In some embodiments, the level of the antibody that binds the antigen of, or derived from, the vaccine is at least about 1.5 times greater than the reference antibody level, such as about any of 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times or more, greater than the reference antibody level.
  • the level of the reference antibody that binds the antigen of, or derived from, the infectious agent is the median level of the reference antibody determined from the population of patients infected with the infectious agent. In some embodiments, the level of the reference antibody that binds the antigen of, or derived from, the infectious agent is the mean level of the reference antibody determined from the population of patients infected with the infectious agent. In some embodiments, the population of patients is at least about 10 patients.
  • each patient of the population of patients has been infected with the infectious agent within about 1 year of determining a level of the reference antibody, such as within about 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 1 year and 1 month, 1 year and 2 months, 1 year and 3 months, 1 year and 4 months, 1 year and 5 months, 1 year and 6 months, or 2 years, of determining a level of the reference antibody.
  • the level of the reference antibody is based on a known or literature value. In some embodiments, the level of the reference antibody is based on a level of the reference antibody in the individual prior to administration of the vaccine. In some embodiments, the level of the reference antibody is based on a population of individuals who have not received the vaccine. In some embodiments, the level of the reference antibody is based on a population of patients having a disease and/or infection targeted by the vaccine. In some embodiments, the population of patients infected with the infectious agent suffered a disease associated with the infectious agent.
  • the isotype of the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent is IgG, IgA, IgM, or a combination thereof. In some embodiments, the isotype of the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent is IgG.
  • the method further comprises comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent.
  • the composition comprises a sample, such as a saliva sample or a nasal sample, from an individual.
  • the sample is collected from the individual following administration of a vaccine against an infectious agent and/or a disease.
  • An antibody profile may comprise evaluating properties, such as antibody levels and/or antibody binding properties, of an antibody in a sample.
  • the antibody profile may comprise, but is not limited to: i) the level of the antibody that binds to an antigen of, or derived from, the vaccine; ii) the presence or absence of an antigen of, or derived from, the vaccine; iii) the signal proportional to the antibody that binds to an antigen of, or derived from, the vaccine; and/or, iv) the quantity of the antibody that binds to an antigen of, or derived from, the vaccine.
  • Techniques for determining an antibody profile are provided herein.
  • the technique detects the antibody that binds to the antigen of, or derived from, the vaccine.
  • the technique quantifies the antibody that binds to the antigen of, or derived from, the vaccine.
  • the technique detects and quantifies the antibody that binds to the antigen of, or derived from, the vaccine.
  • the technique is an ELISA technique, an enzyme-linked immunospot (EPISPOT) technique, an immunoblotting technique (i.e., western blotting), an immunohistochemistry technique, an immunocytochemistry technique, a flow cytometry and fluorescence-activated cell sorting (FACS) technique, or any combination thereof.
  • EPISPOT enzyme-linked immunospot
  • FACS fluorescence-activated cell sorting
  • the technique an ELISA technique. In some embodiments, the ELISA technique is a quantitative ELISA technique.
  • the method comprises determining the antibody profile in a composition comprising a sample, such as a saliva sample or a nasal sample, from an individual, collected from the individual following administration of a vaccine against a disease. In some embodiments, the method comprises determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising the sample from the individual. In some embodiments, the antibody profile is based on the level of the antibody that binds to the antigen of, or derived from, the vaccine.
  • the method further comprises comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent.
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • the infectious agent is a vims.
  • the vaccine is an mRNA vaccine.
  • a method of determining an antibody profile in a composition comprising a sample from an individual that is collected from the individual following administration of a vaccine against a disease.
  • the method comprises determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising the sample from the individual.
  • the antibody profile is based on the level of the antibody that binds to the antigen of, or derived from, the vaccine.
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • the disease is cancer.
  • the antigen is a polypeptide.
  • the polypeptide is present in or on the surface of a cancer cell.
  • the vaccine is an mRNA vaccine.
  • the antibody profile comprises the presence or absence of the antigen of, or derived from, the vaccine. In some embodiments, the presence or absence of the antigen of, or derived from, the vaccine is determined using any of the techniques described herein. In some embodiments, the antibody profile comprises the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine. In some embodiments, the signal is a visual signal. In some embodiments, the signal is a colorimetric, chemiluminescence, or fluorescence signal. In some embodiments, the signal is detected using spectrophotometer, fluorometer, or luminometer.
  • the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine is determined using any of the techniques described herein.
  • the antibody profile comprises the quantity of the antibody that binds to the antigen of, or derived from, the vaccine.
  • the antibody profile comprises the concentration of the antibody that binds to the antigen of, or derived from, the vaccine.
  • the quantity and/or concentration of the antibody that binds to the antigen of, or derived from, the vaccine is determined using any of the techniques described herein.
  • the methods provided herein may involve additional aspects of immunization assessments.
  • the methods may comprise immunizing an individual against a vaccine, assessing a response to a vaccination, selecting an individual for vaccination, evaluating the immunity of an individual against a disease, assessing an antibody that is present in an individual, evaluating (or re-evaluating) an individual based on an emerging variant of an infectious agent, assessing vaccine immunogenicity in an individual following administration of a vaccine against an infectious agent, or any combination thereof.
  • a method of immunizing an individual against a disease comprising assessing whether the individual needs a vaccination (including a repeat or booster vaccination) against the disease using the methods described herein.
  • the method comprises determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva or nasal sample from the individual.
  • the vaccine is against an infectious agent, such as a virus, that is cause by the disease.
  • the vaccine is against a disease, such as cancer.
  • the vaccine is an mRNA vaccine.
  • a method of assessing a response to a vaccination of an individual comprising assessing an immune response in the individual using the methods described herein.
  • the method comprises determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a sample from the individual.
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • the vaccine is against an infectious agent, such as a virus.
  • the vaccine is against a disease, such as cancer.
  • the vaccine is an mRNA vaccine.
  • the method comprises determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a sample from the individual.
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • the vaccine is against an infectious agent, such as a virus.
  • the vaccine is against a disease, such as cancer.
  • the vaccine is an mRNA vaccine.
  • the method comprises determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a sample from the individual.
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • the disease is caused by the infectious agent associated therewith, such as a virus.
  • the disease cancer is caused by the infectious agent associated therewith, such as a virus.
  • a method of assessing an antibody that is present in an individual comprising measuring an antibody that binds to a specific antigen, or portion thereof, using the methods described herein.
  • the method comprises determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a sample from the individual.
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • the antigen is a polypeptide.
  • the polypeptide is on the surface of a cancer cell.
  • the antigen is a spike protein on a virus.
  • a method of evaluating (or re-evaluating) an individual based on an emerging variant of an infectious agent, wherein the individual has been infected or immunized against another variant(s) of the infection agent comprising assessing for the presence of an antibody that provides protection against the other variant(s) using the methods described herein.
  • the method comprises determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a sample from the individual.
  • the sample is a saliva sample.
  • the sample is a nasal sample.
  • the infectious agent is a virus.
  • a method of assessing vaccine immunogenicity in an individual following administration of a vaccine against an infectious agent comprising: determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a sample from the individual, wherein the individual displays vaccine immunogenicity if the antibody that binds to the antigen of, or derived from, the vaccine is present.
  • the sample is a saliva sample.
  • the method further comprises comprising comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • the sample is a nasal sample.
  • the infectious agent is a virus.
  • the methods described herein are useful for assessing vaccine immunogenicity in an individual.
  • Vaccine immunogenicity may be used not only to determine how well a vaccine works in an individual (e.g., the ability to provoke an immune response in an individual), but also the type of immune response that that the vaccine generates over time.
  • the methods are useful for monitoring immunogenicity provided by a vaccine over time.
  • the methods are useful for monitoring residual and/or long-term immunity provided by the vaccine over time.
  • the vaccine immunogenicity is indicative of a level of protective immunity, such as protecting an individual from an infectious agent or developing a disease therefrom.
  • protective immunity comprises preventing an individual from being infected by the an infectious agent and/or suffering from a disease. In some embodiments, protective immunity comprises decreasing the effects (e.g., symptoms) associated with an infectious agent and/or a disease. In some embodiments, protective immunity comprises production of antibodies against the infectious agent and/or disease. In some embodiments, protective immunity comprises production of T cells (e.g., killer T cells) against the infectious agent and/or disease. In some embodiments, the methods described herein are useful for monitoring protective immunity of the vaccine over time. In some embodiments, the vaccine is a vaccine against an infectious agent or disease.
  • kits and/or compositions useful for any of the methods described herein comprises a sample collection device.
  • the kit comprises a sample collection tool, such as an oral swab or a nasal swab.
  • the kit further comprises instructions for collecting a sample, such as a saliva sample and/or a nasal sample.
  • kits and/or composition further comprises reagents useful for the methods described herein.
  • the kit comprises instructions according to the methods described herein.
  • Embodiment 1 A method of assessing vaccine immunogenicity in an individual following administration of a vaccine against an infectious agent, the method comprising: (a) determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva sample from the individual; and (b) comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • Embodiment 2 The method of embodiment 1, wherein the saliva sample is collected by the individual.
  • Embodiment 3 The method of embodiment 1 or 2, wherein the composition comprising the saliva sample comprises a reagent.
  • Embodiment 4 A method of assessing vaccine immunogenicity in an individual following administration of a vaccine against an infectious agent, the method comprising: determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a nasal sample from the individual, wherein the individual displays vaccine immunogenicity if the antibody that binds to the antigen of, or derived from, the vaccine is present.
  • Embodiment 5 The method of embodiment 4, further comprising comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • Embodiment 6 The method of embodiment 4 or 5, wherein the nasal sample is collected by the individual.
  • Embodiment 7 The method of embodiment 6, wherein the nasal sample is collected using a nasal swab.
  • Embodiment 8 The method of any one of embodiments 4-7, wherein the composition comprising the nasal sample comprises a reagent.
  • Embodiment 9 The method of any one of embodiments 1-8, wherein the saliva or nasal sample from the individual is obtained at least about 3 days following administration of the vaccine.
  • Embodiment 10 The method of any one of embodiments 1-9, wherein the saliva or nasal sample from the individual is obtained at least about 10 days following administration of the vaccine.
  • Embodiment 11 The method of any one of embodiments 1-10, wherein the saliva or nasal sample from the individual is obtained at 15 days following administration of the vaccine.
  • Embodiment 12 The method of any one of embodiments 1-11, wherein the administration of the vaccine is the first administration of the vaccine to the individual.
  • Embodiment 13 The method of any one of embodiments 1-11, wherein the administration of the vaccine is the second administration of the vaccine to the individual.
  • Embodiment 14 The method of any one of embodiments 1-3 and 5-13, wherein the level of the reference antibody that binds the antigen of, or derived from, the infectious agent is the median or mean level of the reference antibody determined from the population of patients infected with the infectious agent, and wherein the population of patients is at least about 10 patients.
  • Embodiment 15 The method of embodiment 14, wherein each patient of the population of patients has been infected with the infectious agent within about 1 year of determining a level of the reference antibody.
  • Embodiment 16 The method of any one of embodiments 1-3 and 5-15, wherein the population of patients infected with the infectious agent suffered a disease associated with the infectious agent.
  • Embodiment 17 The method of any one of embodiments 1-16, wherein the antigen of, or derived from, the vaccine and the antigen of, or derived from, the infectious agent are the same.
  • Embodiment 18 The method of any one of embodiments 1-17, wherein the vaccine is an mRNA vaccine.
  • Embodiment 19 The method of any one of embodiments 1-18, wherein the isotype of the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent is selected from the group consisting of IgG, IgA, and IgM, or a combination thereof.
  • Embodiment 20 The method of embodiment 19, wherein the isotype of the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent is the same.
  • Embodiment 21 The method of embodiment 19 or 20, wherein the antibody that binds to the antigen of, or derived from, the vaccine and the reference antibody that binds the antigen of, or derived from, the infectious agent are IgG.
  • Embodiment 22 The method of any one of embodiments 1-21, wherein the infectious agent is a virus.
  • Embodiment 23 The method of embodiment 22, wherein the virus is of the Coronaviridae family.
  • Embodiment 24 The method of embodiment 23, wherein the virus is of the Betacoronavirus genus.
  • Embodiment 25 The method of embodiment 23 or 24, wherein the virus is of the Sarbecovirus subgenus.
  • Embodiment 26 The method of any one of embodiments 23-25, wherein the virus is of the SARSr-CoV species.
  • Embodiment 27 The method of any one of embodiments 23-26, wherein the virus is a SARS-CoV strain.
  • Embodiment 28 The method of embodiment 23, wherein the virus is selected from the group consisting of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Bat SARS-like coronavirus WTVT (Bat SL-CoV-WIVl), alpha coronaviruses 229E (HCoV-229E), New Haven coronavirus NL63 (HCoV-NL63), beta coronaviruses OC43 (HCoV-OC43), coronavirus HKU1 (HCoV- HKU1), and Middle East Respiratory Syndrome coronavirus (MERS-CoV).
  • SARS-CoV-2 Severe Acute Respiratory Syndrome coronavirus 2
  • SARS-CoV Severe Acute Respiratory Syndrome coronavirus
  • Bat SARS-like coronavirus WTVT Bat SL-CoV-WIVl
  • Embodiment 29 The method of any one of embodiments 22-28, wherein the antibody that binds to the antigen of, or derived from, the vaccine binds to a nucleocapsid of the virus.
  • Embodiment 30 The method of any one of embodiments 22-29, wherein the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a nucleocapsid of the virus.
  • Embodiment 31 The method of any one of embodiments 22-28, wherein the antibody that binds to the antigen of, or derived from, the vaccine binds to a spike protein of the virus.
  • Embodiment 32 The method of 31, wherein the antibody that binds to the antigen of, or derived from, the vaccine binds to a SI domain of the spike protein of the virus.
  • Embodiment 33 The method of 31, wherein the antibody that binds to the antigen of, or derived from, the vaccine binds to a S2 domain of the spike protein of the virus.
  • Embodiment 34 The method of any one of embodiments 22-29 and 31-33, wherein the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a spike protein of the virus.
  • Embodiment 35 The method of embodiment 34, wherein the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a SI domain of the spike protein of the virus.
  • Embodiment 36 The method of embodiment 34, wherein the reference antibody that binds the antigen of, or derived from, the infectious agent binds to a S2 domain of the spike protein of the virus.
  • Embodiment 37 The method of any one of embodiments 1-36, wherein determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises measuring the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine in the composition comprising the saliva sample.
  • Embodiment 38 The method of any one of embodiments 1-37, wherein determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises measuring the concentration of the antibody that binds to the antigen of, or derived from, the vaccine in the composition comprising the saliva sample.
  • Embodiment 39 The method of any one of embodiments 1-38, further comprising determining the level of the antibody that binds to the antigen of, or derived from, the vaccine in a saliva sample from the individual acquired from the individual at least 3 months after administration of the vaccine.
  • Embodiment 40 The method of any one of embodiments 1-39, further comprising obtaining the saliva or nasal sample.
  • Embodiment 41 The method of any one of embodiments 1-40, further comprising admixing the saliva or nasal sample with a reagent.
  • Embodiment 42 The method of any one of embodiments 1-41, further comprising a sample processing step.
  • Embodiment 43 The method of any one of embodiments 1-42, wherein determining the level of the antibody that binds to the antigen of, or derived from, the vaccine comprises an ELISA technique.
  • Embodiment 44 The method of embodiment 43, wherein the ELISA technique is a quantitative ELISA technique.
  • Embodiment 45 The method of any one of embodiments 1-44, wherein the infectious agent causes a disease.
  • Embodiment 46 The method of embodiment 45, wherein the disease is Coronavirus Disease-2019 (COVID-19), an Angiotensin-Converting Enzyme 2 (ACE2)-associated disease, Acute Respiratory Distress Syndrome (ARDS), Severe Acute Respiratory Syndrome (SARS), or Middle East respiratory syndrome (MERS).
  • Coronavirus Disease-2019 COVID-19
  • Angiotensin-Converting Enzyme 2 ACE2
  • ARDS Acute Respiratory Distress Syndrome
  • SARS Severe Acute Respiratory Syndrome
  • MERS Middle East respiratory syndrome
  • Embodiment 47 A method of determining an antibody profile in a composition comprising a saliva or nasal sample from an individual, wherein the saliva or nasal sample is collected from the individual following administration of a vaccine against an infectious agent, the method comprising determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising the saliva or nasal sample from the individual, wherein the antibody profile is based on the level of the antibody that binds to the antigen of, or derived from, the vaccine.
  • Embodiment 48 The method of embodiment 47, wherein the antibody profile comprises the presence or absence of the antigen of, or derived from, the vaccine.
  • Embodiment 49 The method of embodiment 47 or 48, wherein the antibody profile comprises the signal proportional to the antibody that binds to the antigen of, or derived from, the vaccine.
  • Embodiment 50 The method of any one of embodiments 47-49, wherein the antibody profile comprises the quantity of the antibody that binds to the antigen of, or derived from, the vaccine.
  • Embodiment 51 The method of any one of embodiments 47-50, further comprising comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent.
  • Embodiment 52 A method of assessing vaccine immunogenicity in an individual following administration of a vaccine against a disease, the method comprising: (a) determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising a saliva or a nasal sample from the individual; and (b) comparing the level of the antibody that binds to the antigen of, or derived from, the vaccine with a reference antibody level, wherein the reference antibody level is based on a level of a reference antibody that binds an antigen of, or derived from, the infectious agent determined from a population of patients infected with the infectious agent, and wherein the individual displays vaccine immunogenicity if the level of the antibody that binds the antigen of, or derived from, the vaccine is equal to or greater than the reference antibody level.
  • Embodiment 53 A method of determining an antibody profile in a composition comprising a saliva or nasal sample from an individual, wherein the saliva or nasal sample is collected from the individual following administration of a vaccine against a disease, the method comprising determining the level of an antibody that binds to an antigen of, or derived from, the vaccine in a composition comprising the saliva or nasal sample from the individual, wherein the antibody profile is based on the level of the antibody that binds to the antigen of, or derived from, the vaccine.
  • Embodiment 54 The method of embodiment 52 or 53, wherein the disease is a cancer.
  • Embodiment 55 The method of any one of embodiments 52-54, wherein the antigen is a polypeptide.
  • Embodiment 56 The method of embodiment 55, wherein the polypeptide is present in or on the surface of a cancer cell.
  • Embodiment 57 The method of any one of embodiments 52-56, wherein the vaccine is an mRNA vaccine. V. Examples Example I
  • This example demonstrates antibody responses observed in saliva samples from individuals who received a SARS-CoV-2 vaccination.
  • Study enrollment was offered to adult frontline workers (aged 18 to 70) who were vaccinated for COVID-19 within 3-7 days of enrollment. 123 study participants were enrolled and 13 were unenrolled due to incomplete sample return. The study comprised participants vaccinated with mRNA vaccines manufactured by Moderna and Pfizer-BioNT. Verbal informed consent was obtained from each participant prior to enrollment in the study and any sample collection. Five days after vaccination, participants were trained to self-collect oral saliva fluid samples and provided specimens under observation for antibody and PCR testing.
  • Saliva specimens were collected using the OraSure® Oral Antibody Collection Devices (OACD); item number 3001-3442-70).
  • OACD OraSure® Oral Antibody Collection Devices
  • the OACD was used according to manufacture instructions. Briefly, the provided pad was brushed 5 times on each side of the lower and upper gums (lower left, lower right, upper left, and upper right gums for a total of 20 times) and then held between the lower gum on one side and the cheek for 2-5 minutes. The pad was then placed into the storage tube, with the provided storage solution. Specimens were kept on ice until they reached the study team. The specimens were processed as recommended by the manufacturer before being aliquoted and stored at -80°C until further use and antibody measurements.
  • the specimens were assessed for the presence of anti-SARS-CoV-2 antibodies, including those generated in response to vaccination.
  • OraSure Technologies SARS-CoV-2 Total Antibody ELISA for oral fluid specimen (item number 3001-3317-70, catalog #1125SB) targeting coronavirus spike protein antigens S 1 and S2 was run manually according to the manufacturer provided protocol. Briefly, 25 pL of provided sample diluent buffer was added to the desired wells of the plate followed by 100 pL of each specimen. Specimens were incubated at ambient temperature for 1 hour.
  • Sample wells were washed six times with a provided wash buffer (20X dilution with ddH?0, 0.35 mL per well), before the provided conjugate solution was added (0.1 mL per well) and incubated at ambient temperature for 1 hour. After a second wash step, the provided substrate solution was added (0.1 mL per well) and incubated at ambient temperature for 30 minutes. The provided stop solution was then added (0.1 mL per well) and absorbance of sample wells measured immediately at 450 nm and 630 nm, with output reports generated with O.D. at 630nm subtracted from O.D. at 450nm.
  • Specimen were classified according to the following: (a) specimens whose S/CO ratio was equal to or exceeding 1.0 were considered positive; (b) specimens with a ratio greater than 0.8 and less than 1.0 were considered equivocal; and (c) specimens with a ratio less than or equal to 0.8 were considered negative. Specimens with ratios in the equivocal range were designated to be rerun for antibody measurement. No specimens in this study fell into the equivocal category.
  • Self-collected oral fluid specimens can detect the quantity of anti-SARS-CoV-2 IgG antibodies among all persons who have received a vaccination for COVID-19 after 15 days with and without a history of COVID-19.
  • the quantity of anti-SARS-CoV-2 IgG antibodies increased and was sustained during the vaccination series.
  • Individuals with a history of COVID-19 experienced a greater initial antibody titer increase and concentration over the time points collected
  • This example demonstrates antibody responses observed in nasal samples from individuals who received a SARS-CoV-2 vaccination.
  • Participant 1 provided a matching oral sample.
  • Participant 2 provided 2 nasal specimens.
  • Nasal specimen were self-collected using iClean flocked swabs according to the following. Each participants removed the swab from the protective pouch and then inserted the entire absorbent tip of the swab into a first nostril of choice (about 3 ⁇ 4 of an inch (1.5 cm) insertion depth). The swab was slowly rotated in a circular path against the inside of a nostril at least 4 times (a total collection period of about 10-15 seconds). The participant then repeated collection in the other nostril using the same collection swab. The swab was then snapped and placed into a storage tube with a provided storage solution (OraSure® Oral Antibody Collection Devices (OACD), item number 3001-3442-70).
  • OACD OraSure® Oral Antibody Collection Devices
  • Each specimen was assessed for antibody response using the ELISA method described in Example 1.
  • antibody concentration from the oral swab was 304.7 ng/mL
  • antibody concentration from the nasal swab was 325.2 ng/mL
  • antibody concentration in the first nasal specimen was 313.2 ng/mL
  • antibody concentration in the second nasal specimen was 329.4 ng/mL.
  • antibody concentration in nasal specimens was determined to be comparable to the concentration of oral antibodies, and antibody concentration in nasal specimens was consistently observed between different samplings and different individuals.

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Abstract

La présente invention concerne, selon certains aspects, des procédés consistant à déterminer un profil d'anticorps dans un échantillon salivaire ou nasal issu d'un individu après l'administration d'un vaccin. Selon certains modes de réalisation, le profil d'anticorps est utile pour évaluer un individu, tel que pour évaluer l'immunogénicité vaccinale et les besoins en traitement vaccinal. Selon d'autres aspects, l'invention concerne des kits et des compositions utiles pour les procédés décrits ici.
PCT/US2022/021129 2021-03-22 2022-03-21 Évaluations d'immunisation à l'aide d'un échantillon salivaire ou nasal WO2022204017A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130224772A1 (en) * 2010-08-26 2013-08-29 University Of Washington Through Its Center For Commercialization Method for detecting anti-he4 antibodies and methods of diagnosis and/or prognosis of conditions associated with he4-expressing cells
US20200196994A1 (en) * 2018-12-19 2020-06-25 Johnson & Johnson Consumer Inc. Devices and Methods for Collecting Saliva Samples from the Oral Cavity

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130224772A1 (en) * 2010-08-26 2013-08-29 University Of Washington Through Its Center For Commercialization Method for detecting anti-he4 antibodies and methods of diagnosis and/or prognosis of conditions associated with he4-expressing cells
US20200196994A1 (en) * 2018-12-19 2020-06-25 Johnson & Johnson Consumer Inc. Devices and Methods for Collecting Saliva Samples from the Oral Cavity

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
KETAS THOMAS J., CHATURBHUJ DEVIDAS, CRUZ-PORTILLO VICTOR M, FRANCOMANO ERIK, GOLDEN ENCOUSE, CHANDRASEKHAR SHARANYA, DEBNATH GARG: "Antibody responses to SARS-CoV-2 mRNA vaccines are detectable in saliva", BIORXIV, 3 November 2021 (2021-11-03), pages 1 - 17, XP055975187, DOI: https://doi.org/10.1101/ 2021.03.11.434841 *
MACMULLAN MELANIE A., CHELLAMUTHU PRITHIVI, MADES AUBREE, DAS SUDIPTA, TURNER FRED, SLEPNEV VLADIMIR I., IBRAYEVA ALBINA: "Detection of SARS-CoV-2 Antibodies in Oral Fluid Obtained Using a Rapid Collection Device", JOURNAL OF CLINICAL MICROBIOLOGY, vol. 59, no. 2, 21 January 2021 (2021-01-21), pages 1 - 9, XP055975192 *
MADES AUBREE, CHELLAMATHU PRITHIVI, KOJIMA NOAH, LOPEZ LAUREN, MACMULLAN MELANIE A., DENNY NICHOLAS, ANGEL AARON N., SANTACRUZ MAR: "Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fuid and upper respiratory tract specimens following COVID-19 mRNA vaccination", NATURE SCIENTIFIC REPORTS, vol. 11, no. 1, 27 December 2021 (2021-12-27), pages 1 - 6, XP055975207 *
MCCULLOCH DENISE J., KIM ASHLEY E., WILCOX NAOMI C., LOGUE JENNIFER K., GRENINGER ALEX L., ENGLUND JANET A., CHU HELEN Y.: "Comparison of Unsupervised Home Self-collected Midnasal Swabs With Clinician-Collected Nasopharyngeal Swabs for Detection of SARS-CoV-2 Infection", JAMA NETWORK OPEN, vol. 3, no. 7, 22 July 2020 (2020-07-22), pages 1 - 4, XP055975189 *
PISANIC NORA, RANDAD PRANAY R., KRUCZYNSKI KATE, MANABE YUKARI C., THOMAS DAVID L., PEKOSZ ANDREW, KLEIN SABRA L., BETENBAUGH MICH: "COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva", JOURNAL OF CLINICAL MICROBIOLOGY, vol. 59, no. 1, 17 December 2020 (2020-12-17), pages 1 - 13, XP055975452 *

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