'O antigenic' polysaccharide specific memory B cell responses in Bangladeshi Cholera patients infected with Vibrio cholerae O1

Abstract

Cholera, caused by Vibrio cholerae O1/O139, is an acute dehydrating enteric disease with high mortality rate if untreated. Several efforts have been made to develop effective vaccines, and effort is still continuing. The available oral cholera vaccines provide protection for 3-5 years in adult and for shorter duration in younger children. However, it was observed that natural infections in cholera endemic areas provide longer term protective immunity lasting for 7-10 years, but the mechanism is not completely understood. It was hypothesized that this protective immunity may be mediated by memory B cell responses. In this study 60 hospitalized cholera culture confirmed patients were evaluated for their immune response up to 180 days after onset of illness. A method of polyclonal stimulation of peripheral blood mononuclear cells followed by an enzyme-linked immunospot assay was used to study memory B cell responses specific to V. cholerae O1 antigens, lipopolysaccharide (LPS) and Ospecific polyscaccharide (OSP) of LPS. To observe circulating plasma antibody responses enzyme-linked immuno assay accompanied with memory B cell studies were carried out at different study points. All patients exhibited LPS and OSP-specific memory B cell proliferation by day 30. LPS-specific IgG and IgM memory B cell responses were elevated throughout the follow up days, while LPS IgA response magnitude waned down by day 90, but persisted up to day 180. However, OSPspecific IgA, IgG and IgM memory B cell response were found at day 30. The OSPspecific IgA and IgG memory B cell responses were elevated throughout the whole study period, while IgM responses started to wane down by day 180. Significant level of LPS and OSP-specific circulating plasma antibody for all the antibody isotypes were observed. Results suggested that such memory B cells might persist for longer period providing protective immunity against subsequent exposure to cholera. A vaccine, targeted to generate memory B cell, preferably OSP-specific will be important for evaluating effectiveness of vaccines and for design and formulation of future effective cholera vaccines.