{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:29:50Z","timestamp":1758122990025},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2000,10,1]],"date-time":"2000-10-01T00:00:00Z","timestamp":970358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,12,24]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>A contraceptive vaccine directed against human chorionic gonadotropin (hCG) has previously undergone clinical testing that demonstrated the feasibility of the approach in preventing pregnancy in women. Some immunized volunteers however, did not respond with an adequate anti-hCG antibody response despite employing highly immunogenic bacterial toxoids as carriers. Since there is some evidence that T cell responses to a complex protein typically focus on a few immunodominant epitopes, we investigated the responsiveness to hCG in mice of different haplotypes using the protein carrier diphtheria toxoid (DT). Our data showed a differential carrier effect of DT. With the aim of making a more potent immunogen employing promiscuous pathogen-derived Th peptides as carriers, peptide:antigen stoichiometric ratios were optimized. When tested individually using alum as the adjuvant, three such peptide conjugates improved the anti-hCG response, though not consistently to levels higher than the DT conjugate. Immunization with a combination of these synthetic epitopes generated anti-hCG responses higher than those achieved with DT or with the individual peptides. Antibodies were of high affinity and capable of neutralizing the bioactivity of hCG, but were devoid of anti-peptide reactivity. These results support our view that differential hyporesponsiveness in a diverse population may arise from inadequate carrier effect and that it can be overcome by use of pathogen-derived broadly reactive non-B Th epitopes employing only alum, a permissible adjuvant.<\/jats:p>","DOI":"10.1046\/j.1365-2249.2000.01351.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T10:23:59Z","timestamp":1047378239000},"page":"101-108","source":"Crossref","is-referenced-by-count":7,"title":["Humoral hyporesponsiveness to a conjugate contraceptive vaccine and its bypass by diverse carriers using permissible adjuvant"],"prefix":"10.1093","volume":"122","author":[{"given":"A","family":"Mandokhot","sequence":"first","affiliation":[{"name":"National Institute of Immunology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Pal","sequence":"additional","affiliation":[{"name":"National Institute of Immunology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Nagpal","sequence":"additional","affiliation":[{"name":"National Institute of Immunology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V S","family":"Chauhan","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering & Biotechnology, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Ahlawat","sequence":"additional","affiliation":[{"name":"National Institute of Immunology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Om","family":"Singh","sequence":"additional","affiliation":[{"name":"National Institute of Immunology and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,12,24]]},"reference":[{"key":"2022011221085162200_b1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1073\/pnas.73.1.218","article-title":"Isoimmunization against human chorionic gonadotropin with conjugates of processed \u03b2-subunit of the hormone and tetanus toxoid","volume":"73","author":"Talwar","year":"1976","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011221085162200_b2","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S0015-0282(16)61024-5","article-title":"Antibody response and characteristics of antibodies in women immunized with three contraceptive vaccines inducing antibodies against human chorionic gonadotropin","volume":"52","author":"Singh","year":"1989","journal-title":"Fertil Steril"},{"key":"2022011221085162200_b3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0010-7824(90)90071-3","article-title":"Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine","volume":"41","author":"Talwar","year":"1990","journal-title":"Contraception"},{"key":"2022011221085162200_b4","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/j.1600-0897.1990.tb00654.x","article-title":"Bioneutralization capacity of the antibodies generated in women by the beta subunit of human chorionic gonadotropin (\u03b2hCG) and \u03b2hCG associated with alpha subunit of ovine luteinizing hormone linked to carriers","volume":"22","author":"Pal","year":"1990","journal-title":"Am J Reprod Immunol"},{"key":"2022011221085162200_b5","doi-asserted-by":"crossref","first-page":"8532","DOI":"10.1073\/pnas.91.18.8532","article-title":"A vaccine that prevents pregnancy in women","volume":"91","author":"Talwar","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011221085162200_b6","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/285664a0","article-title":"Carrier-priming leads to hapten-specific suppression","volume":"285","author":"Herzenberg","year":"1980","journal-title":"Nature"},{"key":"2022011221085162200_b7","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1084\/jem.155.6.1730","article-title":"Epitope-specific regulation: I. 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