PMID- 15213154 OWN - NLM STAT- MEDLINE DCOM- 20040806 LR - 20181113 IS - 0019-9567 (Print) IS - 1098-5522 (Electronic) IS - 0019-9567 (Linking) VI - 72 IP - 7 DP - 2004 Jul TI - Synthetic fragments of Vibrio cholerae O1 Inaba O-specific polysaccharide bound to a protein carrier are immunogenic in mice but do not induce protective antibodies. PG - 4090-101 AB - Development of Vibrio cholerae lipopolysaccharide (LPS) as a cholera vaccine immunogen is justified by the correlation of vibriocidal anti-LPS response with immunity. Two V. cholerae O1 LPS serotypes, Inaba and Ogawa, are associated with endemic and pandemic cholera. Both serotypes induce protective antibody following infection or vaccination. Structurally, the LPSs that define the serotypes are identical except for the terminal perosamine moiety, which has a methoxyl group at position 2 in Ogawa but a hydroxyl group in Inaba. The terminal sugar of the Ogawa LPS is a protective B-cell epitope. We chemically synthesized the terminal hexasaccharides of V. cholerae serotype Ogawa, which comprises in part the O-specific polysaccharide component of the native LPS, and coupled the oligosaccharide at different molar ratios to bovine serum albumin (BSA). Our initial studies with Ogawa immunogens showed that the conjugates induced protective antibody. We hypothesized that antibodies specific for the terminal sugar of Inaba LPS would also be protective. Neoglycoconjugates were prepared from synthetic Inaba oligosaccharides (disaccharide, tetrasaccharide, and hexasaccharide) and BSA at different levels of substitution. BALB/c mice responded to the Inaba carbohydrate (CHO)-BSA conjugates with levels of serum antibodies of comparable magnitude to those of mice immunized with Ogawa CHO-BSA conjugates, but the Inaba-specific antibodies (immunoglobulin M [IgM] and IgG1) were neither vibriocidal nor protective in the infant mouse cholera model. We hypothesize that the anti-Inaba antibodies induced by the Inaba CHO-BSA conjugates have enough affinity to be screened via enzyme-linked immunosorbent assay but not enough to be protective in vivo. FAU - Meeks, Michael D AU - Meeks MD AD - Department of Microbiology and Immunology, Dartmouth Medical School, 630 W. Borwell Bldg., Lebanon, NH 03756, USA. FAU - Saksena, Rina AU - Saksena R FAU - Ma, Xingquan AU - Ma X FAU - Wade, Terri K AU - Wade TK FAU - Taylor, Ronald K AU - Taylor RK FAU - Kovac, Pavol AU - Kovac P FAU - Wade, William F AU - Wade WF LA - eng GR - R01 AI025096/AI/NIAID NIH HHS/United States GR - R37 AI025096/AI/NIAID NIH HHS/United States GR - AI 25096/AI/NIAID NIH HHS/United States GR - AI 47373/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Antibodies) RN - 0 (O Antigens) RN - 27432CM55Q (Serum Albumin, Bovine) SB - IM MH - Animals MH - Antibodies/*immunology MH - Female MH - Mice MH - O Antigens/*immunology/metabolism MH - Serum Albumin, Bovine/metabolism MH - Vibrio cholerae O1/*immunology PMC - PMC427411 EDAT- 2004/06/24 05:00 MHDA- 2004/08/07 05:00 PMCR- 2004/07/01 CRDT- 2004/06/24 05:00 PHST- 2004/06/24 05:00 [pubmed] PHST- 2004/08/07 05:00 [medline] PHST- 2004/06/24 05:00 [entrez] PHST- 2004/07/01 00:00 [pmc-release] AID - 72/7/4090 [pii] AID - 0182-04 [pii] AID - 10.1128/IAI.72.7.4090-4101.2004 [doi] PST - ppublish SO - Infect Immun. 2004 Jul;72(7):4090-101. doi: 10.1128/IAI.72.7.4090-4101.2004.