Preliminary assessment of the safety and immunogenicity of a new CTXPhi-negative, hemagglutinin/protease-defective El Tor strain as a cholera vaccine candidate

Abstract

Vibrio cholerae 638 (El Tor, Ogawa), a new CTXPhi-negative hemagglutinin/protease-defective strain that is a cholera vaccine candidate, was examined for safety and immunogenicity in healthy adult volunteers. In a double-blind placebo-controlled study, no significant adverse reactions were observed in volunteers ingesting strain 638. Four volunteers of 42 who ingested strain 638 and 1 of 14 who received placebo experienced loose stools. The strain strongly colonized the human small bowel, as evidenced by its isolation from the stools of 37 of 42 volunteers. V. cholerae 638, at doses ranging from 4 x 10(7) to 2 x 10(9) vibrios, elicited significant serum vibriocidal antibody and anti-Ogawa immunoglobulin A antibody secreting cell responses.

FIG. 1

Construction of candidate vaccine strain 638. Construction of strain 81 (A) and strain 638 (B). Gene designations: cep, core-encoded pilus; orfU, open reading frame U; ace, accessory cholera enterotoxin; zot, zonula occludens toxin; ctxA, cholera toxin A subunit; ctxB, cholera toxin B subunit; RS1, repeat sequence; hap, hemagglutinin/protease; hap*, 5′ or 3′ half of hap; bla, β-lactamase; celA, C. thermocellum endoglucanase A; oriR6K, R6K origin of replication; mobRP4, RP4 mob (mobilization) region.