A contraceptive vaccine based on the sperm-associated protein catsper

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.

What is claimed is: 
     
         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.