PHASE-1 EVALUATION OF VIBRIO-CHOLERAE O1, SEROTYPE INABA, POLYSACCHARIDE-CHOLERA TOXIN CONJUGATES IN ADULT VOLUNTEERS

Conjugate vaccines were prepared by binding hydrazine-treated lipopoly saccharide (DeALPS) from Vibrio cholerae O1, serotype Inaba, to choler a toxin (CT) variants CT-1 and CT-2. Volunteers (n = 75) were injected with either 25 mu g of DeALPS, alone or as a conjugate, or the licens ed cellular vaccine containing 4 x 10(9) organisms each of serotypes I naba and Ogawa per mi. No serious adverse reactions were observed. DeA LPS alone did not elicit serum LPS or vibriocidal antibodies in mice a nd only low levels of immunoglobulin M (IgM) anti-LPS in the volunteer s. Recipients of the cellular vaccine had the highest IgM anti-LPS lev els, but the difference was not statistically significant from that el icited by the conjugates. The conjugates elicited the highest levels o f IgG anti-LPS (DeALPS-CT-2 > DeALPS-CT-1 > cellular vaccine). Both co njugates and the cellular vaccine elicited vibriocidal antibodies: aft er 8 months, recipients of cellular vaccine had the highest geometric mean titer (1,249), followed by DeALPS-CT-2 (588) and DeALPS-CT-1 (330 ). The correlation coefficient between IgG anti-LPS and 2-mercaptoetha nol (2-ME)-resistant vibriocidal antibodies was 0.81 (P = 0.0004). Con valescent sera from cholera patients had a mean vibriocidal titer of 2 ,525 that was removed by treatment with 2-ME. The vibriocidal activiti es of sera from all vaccine groups and from the patients were absorbed (>75%) by LPS but not by either CT-1 or CT-2. Conjugate-induced IgG v ibriocidal antibodies persisted longer than those elicited by the whol e cell vaccine. Both conjugates, but not the cellular vaccine, elicite d IgG anti-CT.