Antibody-Based Correlates of Protection Against Cholera Analysis of a Challenge Study in a Cholera-Naïve Population

Abstract

Immunologic correlates of protection can be used to infer vaccine efficacy for populations in which challenge trials or field studies are infeasible. In a recent cholera challenge trial (WH Cohen et al, Clinical Infectious Disease 62: 1329-1335, 2016), 134 North American cholera-naïve volunteers were randomized to receive either the live, attenuated single-dose cholera vaccine CVD 103-HgR or placebo, and titers of vibriocidal antibodies against classical Inaba were assessed 10 days after treatment. Subsequent to the immunologic evaluation, each subject ingested a fixed quantity of virulent V. cholerae O1 El Tor Inaba. Data from this trial suggest that vaccine-induced increase in vibriocidal antibody titer prior to challenge is tightly linked with protection: 51/51 vaccinees with post-vaccination vibriocidal titers >= 2560 were protected against moderate/severe cholera, and 60/62 vaccinees who seroconverted, or experienced a 4-fold or greater increase in vibriocidal titer relative to pre-vaccination levels, were similarly protected. Atypically high vibriocidal titers were observed in some placebo subjects; protection was limited in these individuals and differed substantially from the level of protection experienced by vaccinees with the same post-vaccination titers. Since only 1 of 66 placebo recipients experienced seroconversion, seroconversion was found to be uniquely associated with vaccination and insensitive to the effects of factors that can cause titers to be elevated but are weakly associated with protection. Thus, vibriocidal seroconversion was found to be better than vibriocidal titer for inferring vaccine efficacy in cholera-naïve populations for which studies based upon exposure to V. cholerae are impractical.

FIG 1

Overlap of absolute vibriocidal antibody titer distribution in vaccinees and placebo recipients and overlap of fold increase in vibriocidal antibody titer.