{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T01:44:12Z","timestamp":1698889452246},"reference-count":51,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>There is a need for next-generation cholera vaccines that provide high-level and durable protection in young children in cholera-endemic areas. A cholera conjugate vaccine (CCV) is in development to address this need. This vaccine contains the O-specific polysaccharide (OSP) of <jats:italic>Vibrio cholerae<\/jats:italic> O1 conjugated via squaric acid chemistry to a recombinant fragment of the tetanus toxin heavy chain (OSP:rTTHc). This vaccine has been shown previously to be immunogenic and protective in mice and found to be safe in a recent preclinical toxicological analysis in rabbits. We took advantage of excess serum samples collected as part of the toxicological study and assessed the immunogenicity of CCV OSP:rTTHc in rabbits. We found that vaccination with CCV induced OSP-, lipopolysaccharide (LPS)-, and rTTHc-specific immune responses in rabbits, that immune responses were functional as assessed by vibriocidal activity, and that immune responses were protective against death in an established virulent challenge assay. CCV OSP:rTTHc immunogenicity in two animal model systems (mice and rabbits) is encouraging and supports further development of this vaccine for evaluation in humans.<\/jats:p>","DOI":"10.4269\/ajtmh.23-0259","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T14:32:01Z","timestamp":1696257121000},"page":"1122-1128","source":"Crossref","is-referenced-by-count":0,"title":["Vaccination of Rabbits with a Cholera Conjugate Vaccine Comprising O-Specific Polysaccharide and a Recombinant Fragment of Tetanus Toxin Heavy Chain Induces Protective Immune Responses against Vibrio cholerae O1"],"prefix":"10.4269","volume":"109","author":[{"given":"Meagan","family":"Kelly","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suhi","family":"Jeon","sequence":"additional","affiliation":[{"name":"Eubiologics Ltd, Gangnam-gu, Seoul, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeesun","family":"Yun","sequence":"additional","affiliation":[{"name":"Eubiologics Ltd, Gangnam-gu, Seoul, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byungman","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Inha University, Incheon, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minchul","family":"Park","sequence":"additional","affiliation":[{"name":"Eubiologics Ltd, Gangnam-gu, Seoul, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoonhee","family":"Whang","sequence":"additional","affiliation":[{"name":"Eubiologics Ltd, Gangnam-gu, Seoul, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chankyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Eubiologics Ltd, Gangnam-gu, Seoul, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richelle C.","family":"Charles","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taufiqur R.","family":"Bhuiyan","sequence":"additional","affiliation":[{"name":"icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Firdausi","family":"Qadri","sequence":"additional","affiliation":[{"name":"icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Kamruzzaman","sequence":"additional","affiliation":[{"name":"icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somyoung","family":"Cho","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willie F.","family":"Vann","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xu","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, NIH, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavol","family":"Kov\u00e1\u010d","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, NIH, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Ganapathy","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Lynch","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul, South Korea;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward T.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Immunology and Infectious Diseases, Harvard T. 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meta-analysis","volume":"17","author":"Bi","year":"2017"},{"key":"b8","series-title":"Vaccine","first-page":"A132","article-title":"Global oral cholera vaccine use, 2013\u20132018","volume":"38","author":"Pezzoli","year":"2020"},{"key":"b9","series-title":"Trans R Soc Trop Med Hyg","first-page":"251","article-title":"Use of Lot Quality Assurance Sampling (LQAS) to estimate vaccination coverage helps guide future vaccination efforts","volume":"102","author":"Alberti","year":"2008"},{"key":"b10","series-title":"PLoS Negl Trop Dis","first-page":"e0006376","article-title":"Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers","volume":"12","author":"Islam","year":"2018"},{"key":"b11","series-title":"PLoS Negl Trop Dis","first-page":"e0006399","article-title":"Plasma and memory B cell responses 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schedule","volume":"36","author":"Truck","year":"2017"},{"key":"b19","series-title":"Vaccine","first-page":"6936","article-title":"Scalable production and immunogenicity of a cholera conjugate vaccine","volume":"39","author":"Jeon","year":"2021"},{"key":"b20","series-title":"PLoS Negl Trop Dis","first-page":"e0003881","article-title":"A cholera conjugate vaccine containing O-specific polysaccharide (OSP) of V. cholerae O1 Inaba and recombinant fragment of tetanus toxin heavy chain (OSP:rTTHc) induces serum, memory and lamina proprial responses against OSP and is protective in mice","volume":"9","author":"Sayeed","year":"2015"},{"key":"b21","series-title":"PLoS Negl Trop Dis","first-page":"e2683","article-title":"Evaluation in mice of a conjugate vaccine for cholera made from Vibrio cholerae O1 (Ogawa) O-specific polysaccharide","volume":"8","author":"Alam","year":"2014"},{"key":"b22","series-title":"J Infect Dis","first-page":"230","article-title":"Lack of cross-protection against diarrhea due to Vibrio cholerae O139 (Bengal strain) after oral immunization of rabbits with V. cholerae O1 vaccine strain CVD103-HgR","volume":"169","author":"Albert","year":"1994"},{"key":"b23","series-title":"Infect Immun","first-page":"3571","article-title":"Comparison of immune responses in patients infected with Vibrio cholerae O139 and O1","volume":"65","author":"Qadri","year":"1997"},{"key":"b24","series-title":"Proc Natl Acad Sci USA","first-page":"11388","article-title":"The Vibrio cholerae O139 serogroup antigen includes an O-antigen capsule and lipopolysaccharide virulence determinants","volume":"91","author":"Waldor","year":"1994"},{"key":"b25","series-title":"Lancet Microbe","first-page":"e228","article-title":"Predicting Vibrio cholerae infection and symptomatic disease: a systems serology study","volume":"4","author":"Wiens","year":"2023"},{"key":"b26","series-title":"Clin Vaccine Immunol","first-page":"1712","article-title":"Comparison of immune responses to the 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responses to meningococcal group C conjugate and group A and C polysaccharide vaccines in adolescents","volume":"68","author":"Zhang","year":"2000"},{"key":"b38","series-title":"Infect Immun","first-page":"4337","article-title":"Primary and booster mucosal immune responses to meningococcal group A and C conjugate and polysaccharide vaccines administered to university students in the United Kingdom","volume":"69","author":"Zhang","year":"2001"},{"key":"b39","series-title":"Epidemiol Infect","first-page":"201","article-title":"Salivary antibodies following parenteral immunization of infants with a meningococcal serogroup A and C conjugated vaccine","volume":"123","author":"Borrow","year":"1999"},{"key":"b40","series-title":"Vaccine","first-page":"547","article-title":"Salivary antibody response to vaccination with meningococcal A\/C polysaccharide vaccine in previously vaccinated and unvaccinated Gambian 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