title: Evaluation in mice of a conjugate vaccine for cholera made from Vibrio cholerae O1 (Ogawa) O-specific polysaccharide.
abstract: BACKGROUND
  Protective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children.
  
  
  METHODS
  Here we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc) made from V. cholerae O1 Ogawa O-Specific Polysaccharide-core (OSP) and recombinant tetanus toxoid heavy chain fragment (TThc). We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli.
  
  
  RESULTS
  We detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model.
  
  
  CONCLUSIONS
  We describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens.
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
authors: Mohammad Murshid
authors: MM
authors: Alam
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Megan Kelly
authors: MK
authors: Bufano
authors: NIDDK, LBC, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Peng
authors: P
authors: Xu
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Anuj
authors: A
authors: Kalsy
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Y
authors: Y
authors: Yu
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Y Wu
authors: YW
authors: Freeman
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
authors: Tania
authors: T
authors: Sultana
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
authors: Md Rasheduzzaman
authors: MR
authors: Rashu
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Ishaan
authors: I
authors: Desai
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors: Grace
authors: G
authors: Eckhoff
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Daniel T
authors: DT
authors: Leung
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Richelle C
authors: RC
authors: Charles
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Regina C
authors: RC
authors: LaRocque
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Jason B
authors: JB
authors: Harris
authors: Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors: John D
authors: JD
authors: Clements
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Stephen B
authors: SB
authors: Calderwood
authors: International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
authors: Firdausi
authors: F
authors: Qadri
authors: CBER, FDA, Laboratory of Bacterial Toxins, Bethesda, Maryland, United States of America.
authors: W F
authors: WF
authors: Vann
authors: NIDDK, LBC, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Pavol
authors: P
authors: Kováč
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: Edward T
authors: ET
authors: Ryan
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002771:Cholera / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D019081:O Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D019081:O Antigens; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate