Evaluation in Mice of a Conjugate Vaccine for Cholera Made from Vibrio cholerae O1 (Ogawa) O-Specific Polysaccharide

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.methodology: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.principal findings: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.conclusion: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. © 2014.