Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Current oral cholera vaccines induce lower protective efficacy and shorter duration of protection against cholera than wild-type infection provides, and this difference is most pronounced in young children. Despite this, there are limited data comparing immune responses in children following wild-type disease versus vaccination, especially with regard to memory responses associated with long-term immunity. Here, we report a comparison of immune responses in young children (2 to 5 years of age;<jats:italic>n</jats:italic>= 20) and older children (6 to 17 years of age;<jats:italic>n</jats:italic>= 20) given two doses of an oral killed cholera vaccine containing recombinant cholera toxin B subunit (CtxB) 14 days apart and compare these responses to those induced in similarly aged children recovering from infection with<jats:named-content content-type="genus-species">Vibrio cholerae</jats:named-content>O1 Ogawa in Bangladesh. We found that the two vaccine groups had comparable vibriocidal and lipopolysaccharide (LPS)-specific plasma antibody responses. Vaccinees developed lower levels of IgG memory B cell (MBC) responses against CtxB but no significant MBC responses against LPS. In contrast, children recovering from natural cholera infection developed prominent LPS IgG and IgA MBC responses, as well as CtxB IgG MBC responses. Plasma LPS IgG, IgA, and IgM responses, as well as vibriocidal responses, were also significantly higher in children following disease than after vaccination. Our findings suggest that acute and memory immune responses following oral cholera vaccination in children are significantly lower than those observed following wild-type disease, especially responses targeting LPS. These findings may explain, in part, the lower efficacy of oral cholera vaccination in children.</jats:p>

Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

“…We have recently demonstrated that LPSspecific antibody and memory B cell responses are correlated with protection against cholera in household contacts of patients with cholera (14). We have also shown that in children, two doses of WC-rBS vaccine induce significantly lower plasma LPS antibody levels and memory B cell levels than wild-type infection (15). Thus, we hypothesized that differences in V. cholerae polysaccharide-specific humoral responses partly account for differences in the durations of protection provided by infection and vaccination.…”

“…The mechanisms behind these observations are not well understood. We have previously shown that immune responses, including memory B cell responses, to V. cholerae LPS are associated with immunity against cholera (14,27) and that in children memory B cell responses targeting LPS are induced and more sustained by natural infection than by vaccination (15). In this report, we describe the antibody response of child vaccinees and patients against OSP, the component of LPS that defines serogroup specificity and perhaps is an important target of immune responses that mediate protection.…”

“…We analyzed stored plasma samples collected from studies of the WC-rBS vaccine in children from Mirpur, an urban area in Dhaka, Bangladesh (15,18,19). The studies were approved by the Research Review and Ethics Review Committees of the ICDDR,B, Dhaka, Bangladesh.…”

Comparison of Immune Responses to the O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi Adult Patients with Cholera

“…The mechanism underlying the longer protection afforded by natural infection with cholera is not yet fully understood, although memory responses particularly to LPS may play a part (14,18,20,33). Interestingly, current oral killed-cholera vaccines do not induce memory B-cell responses targeting LPS, while wild-type disease does, even in young children (1,24,25).…”

Genomic correlates of variability in immune response to an oral cholera vaccine

“…46 Serum vibriocidal activity, measured by a bactericidal assay requiring the fixation of complement by antibody that is bound specifically to vibrios, is used extensively as a marker of immunity to V. cholerae, but has limitations. 47,48 On the basis of Genomics of response to cholera vaccine PP Majumder et al recent reccommendations 49 to measure LPS-response in multiple immunoglobulin isotypes and results 50,51 which indicate that levels of all immunoglobulin isotypes (IgG, IgM and IgA) determine the nature and extent of protection afforded by oral cholera vaccination, we have used the total anti-LPS AR and also the traditional vibriocidal assay. Clinical trials of many oral vaccines have underscored the importance of understanding the reasons for variability in immune response to oral vaccines, 52 and the identification of genetic factors in the host linked to vaccine immunogenicity.…”