US20220152166A1 - A contraceptive vaccine based on the sperm-associated protein catsper - Google Patents
A contraceptive vaccine based on the sperm-associated protein catsper Download PDFInfo
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- US20220152166A1 US20220152166A1 US17/428,865 US202017428865A US2022152166A1 US 20220152166 A1 US20220152166 A1 US 20220152166A1 US 202017428865 A US202017428865 A US 202017428865A US 2022152166 A1 US2022152166 A1 US 2022152166A1
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- catsper3
- catsper1
- catsper2
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0006—Contraceptive vaccins; Vaccines against sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5256—Virus expressing foreign proteins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5258—Virus-like particles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6075—Viral proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/20011—Papillomaviridae
- C12N2710/20022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/20011—Papillomaviridae
- C12N2710/20023—Virus like particles [VLP]
Definitions
- a contraceptive chimeric virus-like particle including an antigenic carrier domain and one or more antigenic regions from a sperm cell in the antigenic carrier domain.
- the antigenic carrier domain includes one or more capsid proteins.
- the one or more capsid proteins include L1 from human papillomavirus.
- CGP amino acid residues are adjacent the N-terminal end of the one or more antigenic regions and GPC amino acid residues are adjacent the C-terminal end of the one or more antigenic regions.
- the one or more antigenic regions include structural elements of the Catsper ion channel complex.
- the structural elements include at least a portion of one or more loops positioned between the transmembrane helical segments of the Catsper ion channel complex. In some embodiments, the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 s1 and Cat
- the virus-like particle includes SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof.
- Some embodiments of the present disclosure relate to a method of making a contraceptive chimeric virus-like particle including inserting a gene for an antigenic carrier protein into a plasmid, preparing overlapping primers for a chimeric gene of the antigenic carrier and one or more antigenic regions from a sperm cell, performing a polymerase chain reaction to amplify the chimeric gene, and synthesizing a virus-like particle from the chimeric gene.
- the one or more antigenic regions include structural elements of the Catsper ion channel complex.
- the structural elements include at least a portion of one or more loops positioned between the transmembrane helical segments of the Catsper ion channel complex.
- the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsper ⁇ loop 785-805, Catsper ⁇ loop 331-348, or combinations thereof.
- the virus-like particle includes SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof.
- Some embodiments of the present disclosure relate to a method for providing contraceptive treatment to a patient including preparing a composition including a contraceptive chimeric virus-like particle including an antigenic carrier domain and one or more antigenic regions from a sperm cell in the antigenic carrier domain, and administering the composition to a patient to heighten an immune response of the patient to the one or more antigenic regions.
- the antigenic carrier domain includes L1 from human papillomavirus.
- the one or more antigenic regions include structural elements of the Catsper ion channel complex, wherein the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsper ⁇ loop 785-805, Cat
- the one or more antigenic regions includes SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof.
- the composition is administered subcutaneously, intravenously, intranasally, or combinations thereof.
- the method further includes administering a supplemental composition to the patient to reverse the effects of the composition, the supplemental composition including a reversal agent having a protein sequence substantially identical to that of the one or more antigenic regions.
- the reversal agent includes one or more peptides, the one or more peptides include SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof.
- FIG. 1 is a schematic representation of a contraceptive chimeric virus-like particle according to some embodiments of the present disclosure
- FIG. 2 is a chart of a method of making a contraceptive chimeric virus-like particle according to some embodiments of the present disclosure
- FIG. 3A is a chart of a method of providing contraceptive treatment to a patient according to some embodiments of the present disclosure.
- FIG. 3B is a chart of a method of providing contraceptive treatment to a patient according to some embodiments of the present disclosure.
- the contraceptive vaccine provides contraceptive benefits to the user with an effectiveness substantially equivalent to traditional hormonal contraceptives, implanted contraceptives, physical contraceptives, etc.
- the contraceptive vaccine heightens an immune response of the user to a structure present on sperm cells.
- the contraceptive vaccine heightens an immune response of the user to a structure of a protein or combination of proteins present on sperm cells.
- the contraceptive vaccine stimulates production of anti-sperm antibodies in the user.
- the contraceptive vaccine stimulates production of anti-sperm antibodies that, upon, binding to a sperm cell, inhibit the ability of the sperm cell to fertilize an egg cell. In some embodiments, the contraceptive vaccine stimulates production of anti-sperm antibodies that, upon, binding to a sperm cell, inhibit the sperm cell's motility.
- the contraceptive vaccine when administered to women, stimulates production of anti-sperm antibodies, e.g., in the vaginal mucosa, which bind sperm and prevent hyperactive motility in the sperm, rendering the sperm incapable of penetrating an egg.
- the contraceptive vaccine stimulates production of anti-sperm antibodies, e.g., in the epidydimis, which render the sperm substantially inert.
- the contraceptive vaccine includes a contraceptive chimeric virus-like particle (VLP) 100 .
- VLP 100 includes two or more domains 102 .
- VLP 100 includes an antigenic carrier domain 104 .
- antigenic carrier domain 104 includes one or more capsid proteins.
- the one or more capsid proteins include L1 from human papillomavirus.
- VLP 100 includes an antigenic domain 106 .
- antigenic domain 106 includes one or more antigenic regions 106 A.
- antigenic regions 106 A are positioned within the antigenic carrier domain 104 .
- antigenic regions 106 A satisfy one or more of the following: are exposed on or about the sperm cell outer surface, are present only in sperm cells and in no other tissue in the human body, and are required for sperm function.
- antigenic regions 106 A include structural features or portions of structural features from a sperm cell.
- antigenic regions 106 A include structural elements of a protein or combination of proteins present on sperm cells.
- antigenic regions 106 A are present on sperm cell flagellum. In some embodiments, antigenic regions 106 A include structural elements of the Catsper ion channel complex. In some embodiments, antigenic regions 106 A include at least a portion of one or more loops positioned between the transmembrane helical segments of the Catsper ion channel complex.
- antigenic regions 106 A include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsper ⁇ loop 785-805, Catsper ⁇ loop 331-348, or combinations thereof.
- antigenic regions 106 A include SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof.
- CGP amino acid residues are adjacent the N-terminal end of antigenic regions 106 A.
- GPC amino acid residues are adjacent the C-terminal end of one or more antigenic regions 106 A. Without wishing to be bound by theory, these additional residues help stabilize antigenic regions 106 A within antigenic carrier domain 104 .
- VLP 100 include SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof.
- VLP 100 is included in a composition.
- the composition includes one or more preservatives, stabilizers, wetting agents, emulsifiers, buffers, fillers, etc.
- the composition is configured for administration to a user subcutaneously, intravenously, intranasally, or combinations thereof.
- some embodiments of the present disclosure are directed to a method 200 of making a contraceptive chimeric VLP.
- a gene for an antigenic carrier protein is inserted into a plasmid.
- overlapping primers for a chimeric gene of the antigenic carrier and one or more antigenic regions from a sperm cell are prepared.
- the one or more antigenic regions include structural elements of the Catsper ion channel complex, e.g., the structural elements include at least a portion of one or more loops positioned between the transmembrane helical segments of the complex.
- the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsper ⁇ loop 785-805, Catsper ⁇ loop 331-348, or combinations thereof.
- a polymerase chain reaction is performed to amplify the chimeric gene.
- a VLP is synthesized from the chimeric gene.
- the VLP is synthesized in bacterial or yeast cell culture.
- the VLP includes SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof.
- the VLP folds spontaneously.
- the VLP is one or more of VLP 100 discussed above.
- a composition including a contraceptive chimeric VLP including an antigenic carrier domain and one or more antigenic regions from a sperm cell in the antigenic carrier domain is prepared.
- the chimeric VLP is one or more of VLP 100 discussed above.
- the composition is administered to a patient to heighten an immune response of the patient to the one or more antigenic regions.
- the composition is administered to the patient subcutaneously, intravenously, intranasally, or combinations thereof.
- contraceptive immunity is expected to last for about 1 to about 9 years, based on prior experience for women immunized against HPV.
- a supplemental composition is administered to the patient to reverse the effects of the composition.
- the supplemental composition includes a reversal agent having a protein sequence substantially identical to that of the one or more antigenic regions.
- the supplemental composition does not include an antigenic carrier protein.
- the reversal agent includes one or more peptides, the one or more peptides including SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID.
- the supplemental composition includes one or more preservatives, stabilizers, wetting agents, emulsifiers, buffers, fillers, etc.
- the induced immunoinfertility of the composition is reversed by sequestering the anti-sperm antibodies using overdosing with the supplemental composition.
- a window of fertility may be created by the application of a reversal agent.
- chimeric L1 VLP forming proteins that include short antigenic segments from the sperm cationic ion channel Catsper were prepared. Antigenic segments of Catsper were predicted by identifying extracellular loops using the homology model. Site of insertion into the L1 gene were identified by multiple sequence alignment of homolog papilloma virus L1 sequences. Three candidate insertion sites were identified as sites of natural insertion/deletion. Bracketing CGP . . . GPC sequences were added to stabilize the inserted loop. DNA sequences were designed using DNAWorks.
- the gene for HPV Type 11 L1 was synthesized using the assembly PCR method. The gene was inserted into the pET28a+ vector at NdeI and EcoRI cloning sites. The plasmid was grown and purified from cell culture using Escherichia coli strain DH5 ⁇ . Chimeric constructs were made by amplifying the plasmid (inverse PCR) using overlapping oligos including the sequence of the desired antigenic region. Amplicons were transformed into DH5 ⁇ cells for plasmid amplification, and were moved into BL21(DE3)pLysS cells for protein expression.
- IB Isolation of inclusion body (IB).
- Recombinant proteins L1 protein of HPV Type 11 (L1), L1 with Catsper loop S3-S4 (P1), and L1 with Catsper-Epsilon loop 331-348 (C5) were expressed in E. coli.
- Recombinant proteins (L1, P1 and C5) were purified from inclusion bodies (IBs) isolated from E. coli Bl21(DE3) transformed by the plasmid constructs pET28a-L1-P1 and pET28a-L1-C5. Cells from a 500 ml culture of transformed E. coli cells, after induction for recombinant protein synthesis, were harvested.
- the wet cell biomass approximately 1 g in weight, was suspended in 25 ml of buffer (50 mM Tris, 50 mM NaCl, pH 9.5) by gentle stirring. The suspension was subjected to sonication (15 cycles, 10 Sec on and 10 sec off in ice) and then centrifuged for 20 min at 12,000 g at 4° C. to pellet the IBs. Harvested IBs were washed twice with wash buffer 50 mM Tris (pH 9.5).
- buffer 50 mM Tris, 50 mM NaCl, pH 9.5
- Solubilization and refolding Comparatively purified IBs were solubilized in 5 ml of solubilization buffer (50 mM Tris (pH 9.5), 50 mM NaCl, 50 mM NaCl, 8 M urea), and stirred gently at room temperature for 2 h. The resultant suspension was centrifuged at 11000 rpm for 36 min at 25° C. to collect total soluble protein.
- solubilization buffer 50 mM Tris (pH 9.5), 50 mM NaCl, 50 mM NaCl, 8 M urea
- Solubilized IBs were refolded in 10 volumes of ice cold refolding buffer (50 mM Tris, 50 mM NaCl, 5% ⁇ -mercaptoethanol and 100 mM L-Arginine (pH9.5)) using pulsatile dilution method at a rate of approximately 0.1 ml/min. Refolded protein was centrifuged at 11000 rpm for 45 minutes at 4° C.
- VLP Virus-like particles
- Methods and system according to some embodiments of the present disclosure are directed to a contraceptive vaccine for providing long-lasting yet reversible contraceptive effects.
- the structure of the contraceptive vaccine stimulates an immune response to antigens present only in sperm cells, with the resulting anti-sperm antibodies effective to bind sperm and render those cells incapable of fertilization.
- the production and use of the contraceptive vaccine are simple. The need for hormone treatment and/or surgery are avoided as no action beyond vaccination is necessary to realize the benefits of the compositions of the present disclosure.
- the contraceptive immunity is easily and immediately reversible, with the immunity returning automatically to the contraceptive state with time as well.
Abstract
A composition includes a contraceptive chimeric virus-like particle with an antigenic carrier domain and one or more antigenic regions from a sperm cell in the antigenic carrier domain, with the antigenic carrier domain including human papillomavirus L1 capsid protein and the antigenic regions including one or more structural elements of the Catsper ion channel complex. When administered to a patient, the contraceptive vaccine stimulates production of anti-sperm antibodies that, upon binding to a sperm cell, inhibit the sperm cell's motility and thus inhibit the ability of the sperm cell to fertilize an egg cell. The induced immunoinfertility of the composition can be reversed for brief or extended lengths of time by overdosing the patient with a reversal agent lacking the antigenic carrier domain but having a protein sequence substantially identical to that of the one or more antigenic regions to sequester the anti-sperm antibodies.
Description
- This application is a national stage filing of International Patent Application No. PCT/US2020/017449, filed Feb. 10, 2020, which claims the benefit of U.S. Provisional Application Nos. 62/802,922, filed Feb. 8, 2019, and 62/970,249, filed Feb. 5, 2020, which are incorporated by reference as if disclosed herein in their entireties.
- Almost half of all pregnancies worldwide are unwanted or mistimed. Current long-acting reversible contraceptive technology is focused on hormonal methods or surgery. Despite their overall effectiveness, there are myriad drawbacks to the contraceptive technologies available to women and men. By way of example, some women cannot tolerate hormonal contraception. Further, hormonal methods often require significant discipline or discomfort in the patient. For example, a regimen of pills or patches need to be taken or applied at regular intervals over the time that the contraceptive effect is desired. Implanted or intrauterine devices can cause mild to severe side-effects and complications, and still may require a clinical visit for reversal or for reimplantation.
- What is desired, therefore, is an effective, long-lasting, and reversible contraceptive treatment with increased ease of use that also reduces the treatment-related burden on the patients desiring the contraceptive effects.
- Accordingly, some embodiments of the present disclosure relate to a contraceptive chimeric virus-like particle including an antigenic carrier domain and one or more antigenic regions from a sperm cell in the antigenic carrier domain. In some embodiments, the antigenic carrier domain includes one or more capsid proteins. In some embodiments, the one or more capsid proteins include L1 from human papillomavirus. In some embodiments, CGP amino acid residues are adjacent the N-terminal end of the one or more antigenic regions and GPC amino acid residues are adjacent the C-terminal end of the one or more antigenic regions. In some embodiments, the one or more antigenic regions include structural elements of the Catsper ion channel complex. In some embodiments, the structural elements include at least a portion of one or more loops positioned between the transmembrane helical segments of the Catsper ion channel complex. In some embodiments, the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsperδ loop 785-805, Catsperε loop 331-348, or combinations thereof. In some embodiments, the virus-like particle includes SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof.
- Some embodiments of the present disclosure relate to a method of making a contraceptive chimeric virus-like particle including inserting a gene for an antigenic carrier protein into a plasmid, preparing overlapping primers for a chimeric gene of the antigenic carrier and one or more antigenic regions from a sperm cell, performing a polymerase chain reaction to amplify the chimeric gene, and synthesizing a virus-like particle from the chimeric gene. In some embodiments, the one or more antigenic regions include structural elements of the Catsper ion channel complex. In some embodiments, the structural elements include at least a portion of one or more loops positioned between the transmembrane helical segments of the Catsper ion channel complex. In some embodiments, the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsperδ loop 785-805, Catsperε loop 331-348, or combinations thereof. In some embodiments, the virus-like particle includes SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof.
- Some embodiments of the present disclosure relate to a method for providing contraceptive treatment to a patient including preparing a composition including a contraceptive chimeric virus-like particle including an antigenic carrier domain and one or more antigenic regions from a sperm cell in the antigenic carrier domain, and administering the composition to a patient to heighten an immune response of the patient to the one or more antigenic regions. In some embodiments, the antigenic carrier domain includes L1 from human papillomavirus. In some embodiments, the one or more antigenic regions include structural elements of the Catsper ion channel complex, wherein the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsperδ loop 785-805, Catsperε loop 331-348, or combinations thereof. In some embodiments, the one or more antigenic regions includes SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof. In some embodiments, the composition is administered subcutaneously, intravenously, intranasally, or combinations thereof. In some embodiments, the method further includes administering a supplemental composition to the patient to reverse the effects of the composition, the supplemental composition including a reversal agent having a protein sequence substantially identical to that of the one or more antigenic regions. In some embodiments, the reversal agent includes one or more peptides, the one or more peptides include SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof.
- The drawings show embodiments of the disclosed subject matter for the purpose of illustrating the invention. However, it should be understood that the present application is not limited to the precise arrangements and instrumentalities shown in the drawings, wherein:
-
FIG. 1 is a schematic representation of a contraceptive chimeric virus-like particle according to some embodiments of the present disclosure; -
FIG. 2 is a chart of a method of making a contraceptive chimeric virus-like particle according to some embodiments of the present disclosure; -
FIG. 3A is a chart of a method of providing contraceptive treatment to a patient according to some embodiments of the present disclosure; and -
FIG. 3B is a chart of a method of providing contraceptive treatment to a patient according to some embodiments of the present disclosure. - Referring now to
FIG. 1 , some embodiments of the present disclosure are directed to a vaccine for providing contraceptive treatment to an individual, user, patient, etc. In some embodiments, the contraceptive vaccine provides contraceptive benefits to the user with an effectiveness substantially equivalent to traditional hormonal contraceptives, implanted contraceptives, physical contraceptives, etc. In some embodiments, the contraceptive vaccine heightens an immune response of the user to a structure present on sperm cells. In some embodiments, the contraceptive vaccine heightens an immune response of the user to a structure of a protein or combination of proteins present on sperm cells. In some embodiments, the contraceptive vaccine stimulates production of anti-sperm antibodies in the user. In some embodiments, the contraceptive vaccine stimulates production of anti-sperm antibodies that, upon, binding to a sperm cell, inhibit the ability of the sperm cell to fertilize an egg cell. In some embodiments, the contraceptive vaccine stimulates production of anti-sperm antibodies that, upon, binding to a sperm cell, inhibit the sperm cell's motility. Without wishing to be bound by theory, when administered to women, the contraceptive vaccine stimulates production of anti-sperm antibodies, e.g., in the vaginal mucosa, which bind sperm and prevent hyperactive motility in the sperm, rendering the sperm incapable of penetrating an egg. Again without wishing to be bound by theory, when administered to men, the contraceptive vaccine stimulates production of anti-sperm antibodies, e.g., in the epidydimis, which render the sperm substantially inert. - In some embodiments, the contraceptive vaccine includes a contraceptive chimeric virus-like particle (VLP) 100. In some embodiments,
VLP 100 includes two ormore domains 102. In some embodiments,VLP 100 includes anantigenic carrier domain 104. In some embodiments,antigenic carrier domain 104 includes one or more capsid proteins. In some embodiments, the one or more capsid proteins include L1 from human papillomavirus. - In some embodiments,
VLP 100 includes anantigenic domain 106. In some embodiments,antigenic domain 106 includes one or moreantigenic regions 106A. In some embodiments,antigenic regions 106A are positioned within theantigenic carrier domain 104. In some embodiments,antigenic regions 106A satisfy one or more of the following: are exposed on or about the sperm cell outer surface, are present only in sperm cells and in no other tissue in the human body, and are required for sperm function. In some embodiments,antigenic regions 106A include structural features or portions of structural features from a sperm cell. In some embodiments,antigenic regions 106A include structural elements of a protein or combination of proteins present on sperm cells. In some embodiments,antigenic regions 106A are present on sperm cell flagellum. In some embodiments,antigenic regions 106A include structural elements of the Catsper ion channel complex. In some embodiments,antigenic regions 106A include at least a portion of one or more loops positioned between the transmembrane helical segments of the Catsper ion channel complex. In some embodiments,antigenic regions 106A include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsperδ loop 785-805, Catsperε loop 331-348, or combinations thereof. In some embodiments,antigenic regions 106A include SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof. - In some embodiments, CGP amino acid residues are adjacent the N-terminal end of
antigenic regions 106A. In some embodiments, GPC amino acid residues are adjacent the C-terminal end of one or moreantigenic regions 106A. Without wishing to be bound by theory, these additional residues help stabilizeantigenic regions 106A withinantigenic carrier domain 104. In some embodiments,VLP 100 include SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof. - In some embodiments,
VLP 100 is included in a composition. In some embodiments, the composition includes one or more preservatives, stabilizers, wetting agents, emulsifiers, buffers, fillers, etc. In some embodiments, the composition is configured for administration to a user subcutaneously, intravenously, intranasally, or combinations thereof. - Referring now to
FIG. 2 , some embodiments of the present disclosure are directed to amethod 200 of making a contraceptive chimeric VLP. At 202, a gene for an antigenic carrier protein is inserted into a plasmid. At 204, overlapping primers for a chimeric gene of the antigenic carrier and one or more antigenic regions from a sperm cell are prepared. As discussed above, in some embodiments, the one or more antigenic regions include structural elements of the Catsper ion channel complex, e.g., the structural elements include at least a portion of one or more loops positioned between the transmembrane helical segments of the complex. In some embodiments, the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsperδ loop 785-805, Catsperε loop 331-348, or combinations thereof. At 206, a polymerase chain reaction is performed to amplify the chimeric gene. At 208, a VLP is synthesized from the chimeric gene. In some embodiments, the VLP is synthesized in bacterial or yeast cell culture. In some embodiments, the VLP includes SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof. In some embodiments, the VLP folds spontaneously. In some embodiments, the VLP is one or more ofVLP 100 discussed above. - Referring now to
FIG. 3A , some embodiments of the present disclosure are directed to amethod 300 for providing contraceptive treatment to a patient. At 302, a composition including a contraceptive chimeric VLP including an antigenic carrier domain and one or more antigenic regions from a sperm cell in the antigenic carrier domain is prepared. In some embodiments, the chimeric VLP is one or more ofVLP 100 discussed above. At 304, the composition is administered to a patient to heighten an immune response of the patient to the one or more antigenic regions. In some embodiments, the composition is administered to the patient subcutaneously, intravenously, intranasally, or combinations thereof. Without wishing to be bound by theory, contraceptive immunity is expected to last for about 1 to about 9 years, based on prior experience for women immunized against HPV. - Referring now to
FIG. 3B , in some embodiments, at 306, a supplemental composition is administered to the patient to reverse the effects of the composition. In some embodiments, the supplemental composition includes a reversal agent having a protein sequence substantially identical to that of the one or more antigenic regions. In some embodiments, the supplemental composition does not include an antigenic carrier protein. In some embodiments, the reversal agent includes one or more peptides, the one or more peptides including SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof. In some embodiments, the supplemental composition includes one or more preservatives, stabilizers, wetting agents, emulsifiers, buffers, fillers, etc. Without wishing to be bound by theory, the induced immunoinfertility of the composition is reversed by sequestering the anti-sperm antibodies using overdosing with the supplemental composition. In some embodiments, in the event that a sperm-immune individual wishes to recover fertility for a short period of time, a window of fertility may be created by the application of a reversal agent. - Design of chimeric L1. By way of example, chimeric L1 VLP forming proteins that include short antigenic segments from the sperm cationic ion channel Catsper were prepared. Antigenic segments of Catsper were predicted by identifying extracellular loops using the homology model. Site of insertion into the L1 gene were identified by multiple sequence alignment of homolog papilloma virus L1 sequences. Three candidate insertion sites were identified as sites of natural insertion/deletion. Bracketing CGP . . . GPC sequences were added to stabilize the inserted loop. DNA sequences were designed using DNAWorks.
- Cloning of chimeric L1. The gene for HPV Type 11 L1 was synthesized using the assembly PCR method. The gene was inserted into the pET28a+ vector at NdeI and EcoRI cloning sites. The plasmid was grown and purified from cell culture using Escherichia coli strain DH5α. Chimeric constructs were made by amplifying the plasmid (inverse PCR) using overlapping oligos including the sequence of the desired antigenic region. Amplicons were transformed into DH5α cells for plasmid amplification, and were moved into BL21(DE3)pLysS cells for protein expression.
- Isolation of inclusion body (IB). Recombinant proteins L1 protein of HPV Type 11 (L1), L1 with Catsper loop S3-S4 (P1), and L1 with Catsper-Epsilon loop 331-348 (C5) were expressed in E. coli. Recombinant proteins (L1, P1 and C5) were purified from inclusion bodies (IBs) isolated from E. coli Bl21(DE3) transformed by the plasmid constructs pET28a-L1-P1 and pET28a-L1-C5. Cells from a 500 ml culture of transformed E. coli cells, after induction for recombinant protein synthesis, were harvested. The wet cell biomass, approximately 1 g in weight, was suspended in 25 ml of buffer (50 mM Tris, 50 mM NaCl, pH 9.5) by gentle stirring. The suspension was subjected to sonication (15 cycles, 10 Sec on and 10 sec off in ice) and then centrifuged for 20 min at 12,000 g at 4° C. to pellet the IBs. Harvested IBs were washed twice with wash buffer 50 mM Tris (pH 9.5).
- Solubilization and refolding. Comparatively purified IBs were solubilized in 5 ml of solubilization buffer (50 mM Tris (pH 9.5), 50 mM NaCl, 50 mM NaCl, 8 M urea), and stirred gently at room temperature for 2 h. The resultant suspension was centrifuged at 11000 rpm for 36 min at 25° C. to collect total soluble protein. Solubilized IBs were refolded in 10 volumes of ice cold refolding buffer (50 mM Tris, 50 mM NaCl, 5% β-mercaptoethanol and 100 mM L-Arginine (pH9.5)) using pulsatile dilution method at a rate of approximately 0.1 ml/min. Refolded protein was centrifuged at 11000 rpm for 45 minutes at 4° C.
- Dialysis and in vitro assembly of Virus-like particles (VLP). Refolded protein was filtered through 0.2 μm filter (VWR) and dialyzed against dialysis buffer (50 mM Tris, 100 mM NaCl, pH 9.5) using 12-14 kDa cut off dialysis membrane (Spectra/Por, VWR) at 4° C. NaCl concentration was increased stepwise up to 500 mM after three changes of dialysis buffer at 3 h intervals. Final dialysis was carried out for 2 h against high salt buffer (50 mM Tris, 500 mM NaCl, pH 9.5).
- Methods and system according to some embodiments of the present disclosure are directed to a contraceptive vaccine for providing long-lasting yet reversible contraceptive effects. The structure of the contraceptive vaccine stimulates an immune response to antigens present only in sperm cells, with the resulting anti-sperm antibodies effective to bind sperm and render those cells incapable of fertilization. The production and use of the contraceptive vaccine are simple. The need for hormone treatment and/or surgery are avoided as no action beyond vaccination is necessary to realize the benefits of the compositions of the present disclosure. Finally, the contraceptive immunity is easily and immediately reversible, with the immunity returning automatically to the contraceptive state with time as well.
- Although the invention has been described and illustrated with respect to exemplary embodiments thereof, it should be understood by those skilled in the art that the foregoing and various other changes, omissions and additions may be made therein and thereto, without parting from the spirit and scope of the present invention.
Claims (20)
1. A contraceptive chimeric virus-like particle, comprising:
an antigenic carrier domain; and
one or more antigenic regions from a sperm cell in the antigenic carrier domain.
2. The chimeric virus-like particle according to claim 1 , wherein the antigenic carrier domain includes one or more capsid proteins.
3. The chimeric virus-like particle according to claim 2 , wherein the one or more capsid proteins include L1 from human papillomavirus.
4. The chimeric virus-like particle according to claim 1 , wherein CGP amino acid residues are adjacent the N-terminal end of the one or more antigenic regions and GPC amino acid residues are adjacent the C-terminal end of the one or more antigenic regions.
5. The chimeric virus-like particle according to claim 1 , wherein the one or more antigenic regions include structural elements of the Catsper ion channel complex.
6. The chimeric virus-like particle according to claim 5 , wherein the structural elements include at least a portion of one or more loops positioned between the transmembrane helical segments of the Catsper ion channel complex.
7. The chimeric virus-like particle according to claim 6 , wherein the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsperδ loop 785-805, Catsperε loop 331-348, or combinations thereof.
8. The chimeric virus-like particle according to claim 7 , wherein the virus-like particle includes SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof.
9. A method of making a contraceptive chimeric virus-like particle, comprising:
inserting a gene for an antigenic carrier protein into a plasmid;
preparing overlapping primers for a chimeric gene of the antigenic carrier and one or more antigenic regions from a sperm cell;
performing a polymerase chain reaction to amplify the chimeric gene; and
synthesizing a virus-like particle from the chimeric gene.
10. The method according to claim 9 , wherein the one or more antigenic regions include structural elements of the Catsper ion channel complex.
11. The method according to claim 10 , wherein the structural elements include at least a portion of one or more loops positioned between the transmembrane helical segments of the Catsper ion channel complex.
12. The method according to claim 11 , wherein the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsperδ loop 785-805, Catsperε loop 331-348, or combinations thereof.
13. The method according to claim 12 , wherein the virus-like particle includes SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, or combinations thereof.
14. A method for providing contraceptive treatment to a patient, comprising:
preparing a composition including a contraceptive chimeric virus-like particle including an antigenic carrier domain and one or more antigenic regions from a sperm cell in the antigenic carrier domain; and
administering the composition to a patient to heighten an immune response of the patient to the one or more antigenic regions.
15. The method according to claim 14 , wherein the antigenic carrier domain includes L1 from human papillomavirus.
16. The method according to claim 14 , wherein the one or more antigenic regions include structural elements of the Catsper ion channel complex, wherein the structural elements include at least a portion of: the loop between Catsper1 s1 and Catsper1 s2, the loop between Catsper2 s5 and Catsper2 p-loop, the loop between Catsper1 s3 and Catsper1 s4, the loop between Catsper2 s1 and Catsper2 s2, the loop between Catsper3 s1 and Catsper3 s2, the loop between Catsper1 s5 and Catsper1 p-loop, the loop between Catsper2 p-loop and Catsper2 s6, the loop between Catsper3 s3 and Catsper3 s4, the loop between Catsper3 s5 and Catsper3 p-loop, the loop between Catsper3 p-loop and Catsper3 s6, the loop between Catsper4 s1 and Catsper4 s2, the loop between Catsper4 p-loop and Catsper4 s6, Catsperδ loop 785-805, Catsperε loop 331-348, or combinations thereof.
17. The method according to claim 16 , wherein the one or more antigenic regions includes SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof.
18. The method according to claim 14 , wherein the composition is administered subcutaneously, intravenously, intranasally, or combinations thereof.
19. The method according to claim 14 , further comprising:
administering a supplemental composition to the patient to reverse the effects of the composition, the supplemental composition including a reversal agent having a protein sequence substantially identical to that of the one or more antigenic regions.
20. The method according to claim 19 , wherein the reversal agent includes one or more peptides, the one or more peptides include SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12, SEQ. ID. NO.: 13, SEQ. ID. NO.: 14, SEQ. ID. NO.: 15, SEQ. ID. NO.: 16, SEQ. ID. NO.: 17, SEQ. ID. NO.: 18, SEQ. ID. NO.: 19, SEQ. ID. NO.: 20, SEQ. ID. NO.: 21, SEQ. ID. NO.: 22, or combinations thereof.
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US17/428,865 US20220152166A1 (en) | 2019-02-08 | 2020-02-10 | A contraceptive vaccine based on the sperm-associated protein catsper |
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US201962802922P | 2019-02-08 | 2019-02-08 | |
US202062970249P | 2020-02-05 | 2020-02-05 | |
PCT/US2020/017449 WO2020163853A1 (en) | 2019-02-08 | 2020-02-10 | A contraceptive vaccine based on the sperm-associated protein catsper |
US17/428,865 US20220152166A1 (en) | 2019-02-08 | 2020-02-10 | A contraceptive vaccine based on the sperm-associated protein catsper |
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US17/428,865 Abandoned US20220152166A1 (en) | 2019-02-08 | 2020-02-10 | A contraceptive vaccine based on the sperm-associated protein catsper |
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US (1) | US20220152166A1 (en) |
EP (1) | EP3920967A4 (en) |
JP (1) | JP2022519518A (en) |
CN (1) | CN113454210A (en) |
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WO (1) | WO2020163853A1 (en) |
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SE514982C2 (en) * | 1999-09-30 | 2001-05-28 | Active Biotech Ab | Carrier containing a major capsid protein L1 from human papillomavirus and its use |
US7189405B1 (en) * | 1999-10-29 | 2007-03-13 | Rice Peter A | Peptide mimics of conserved gonococcal epitopes and methods and compositions using them |
MXPA03010069A (en) * | 2001-05-03 | 2004-04-02 | Childrens Medical Center | Sperm-specific cation channel, and uses therefor. |
GB0212067D0 (en) * | 2002-05-24 | 2002-07-03 | Impharmatica Ltd | Proteins |
AU2007291936B2 (en) * | 2006-08-30 | 2012-09-27 | Artes Biotechnology Gmbh | Recombinant proteins and virus like particles comprising L and S polypeptides of avian hepadnaviridae and methods, nucleic acid constructs, vectors and host cells for producing same |
CN101747424A (en) * | 2008-12-19 | 2010-06-23 | 华中科技大学 | Polypeptide for male immunocontraception |
CN101816799B (en) * | 2010-04-09 | 2011-12-07 | 中国人民解放军第三军医大学 | Gene vaccine of sperm-specific cationic channel protein CatSper1 and preparation method thereof |
WO2014120975A1 (en) * | 2013-02-01 | 2014-08-07 | California Institute Of Technology | Antibody-mediated immunocontraception |
CA3002819A1 (en) * | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Sexually transmitted disease vaccines |
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- 2020-02-10 JP JP2021544400A patent/JP2022519518A/en active Pending
- 2020-02-10 CN CN202080013310.0A patent/CN113454210A/en active Pending
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CN113454210A (en) | 2021-09-28 |
AU2020218564A1 (en) | 2021-08-19 |
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