Impaired immune response to natural infection as a correlate of vaccine failure in a field trial of killed oral cholera vaccines

Abstract

In a field trial carried out in 1985 in Matlab, Bangladesh, the authors evaluated whether subjects who developed Vibrio cholerae 01 infections during the first year after earlier receipt of B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) oral cholera vaccines exhibited deficient serum vibriocidal immune responses to these infections. After severe V. cholerae 01 infections (n = 70) in subjects > 5 years of age, the age group in which both vaccines were efficacious, a 6.5 geometric mean-fold rise of serum vibriocidal antibodies was observed among vaccinees, compared with an 18.6 geometric mean-fold rise in placebo-recipients (p < 0.01). Depressions of serum vibriocidal responses among vaccinees were even more marked after asymptomatic infections (n = 30): a 1.1 geometric mean-fold rise in vaccinees versus a 5.9 geometric mean-fold rise in placebo-recipients (p < 0.01). The authors conclude that subjects who failed to be protected by BS-WC and WC, despite being in the age group for which these vaccines were protective, exhibited poor immune responses even to the vigorous stimulus of natural infection. These findings raise the possibility that immune hyporesponsiveness may limit the potential efficacy attainable by cholera vaccines in populations with endemic cholera.

PIP: Natural infections by Vibrio cholerae 01 are known to confer substantial protection against recurrent infections in populations where cholera is endemic. This suggests that it may one day be possible to develop a highly effective oral vaccine against cholera. It is, however, curious that cholera continues to occur into adulthood in populations which have endemic cholera. This phenomenon could be the result of an inability among some individuals in endemic populations to mount suitable immune responses to natural infections. If such immune hyporesponsiveness is truly at work, it may be an important barrier against the development and use of an effective oral cholera vaccine. The authors evaluated whether deficient immune responses to natural infection were associated with the risk of vaccine failure among recipients of killed oral cholera vaccines in a field trial in Bangladesh during 1985. Their findings support the hypothesis that immune hyporesponsiveness, even after the vigorous stimulus of natural infection, may have limited the protection conferred by the vaccines studied in the trial.