Induction of systemic, mucosal and memory antibody responses targeting Vibrio cholerae O1 O-specific polysaccharide (OSP) in adults following oral vaccination with an oral killed whole cell cholera vaccine in Bangladesh

Abstract

Background Oral cholera vaccine (OCV) containing killed Vibrio cholerae O1 and O139 organisms (Bivalent-OCV; Biv-OCV) are playing a central role in global cholera control strategies. OCV is currently administered in a 2-dose regimen (day 0 and 14). There is a growing body of evidence that immune responses targeting the O-specific polysaccharide (OSP) of V . cholerae mediate protection against cholera. There are limited data on anti-OSP responses in recipients of Biv-OCV. We assessed serum antibody responses against O1 OSP, as well as antibody secreting cell (ASC) responses (a surrogate marker for mucosal immunity) and memory B cell responses in blood of adult recipients of Biv-OCV in Dhaka, Bangladesh. Methodology/Principal findings We enrolled 30 healthy adults in this study and administered two doses of OCV (Shanchol) at days 0 and 14. Blood samples were collected before vaccination (day 0) and 7 days after each vaccination (day 7 and day 21), as well as on day 44. Serum responses were largely IgA with minimal IgG and IgM responses in this population. There was no appreciable boosting following day 14 vaccination. There were significant anti-OSP IgA ASC responses on day 7 following the first vaccination, but none after the second immunization. Anti-OSP IgA memory B cell responses were detectable 30 days after completion of the vaccination series, with no evident induction of IgG memory responses. In this population, anti-Ogawa OSP responses were more prominent than anti-Inaba responses, perhaps reflecting impact of previous exposure. Serum anti-OSP responses returned to baseline within 30 days of completing the vaccine series. Conclusion Our results call into question the utility of the 2-dose regimen separated by 14 days in adults in cholera endemic areas, and also suggest that Biv-OCV-induced immune responses targeting OSP are largely IgA in this highly endemic cholera area. Studies in children in cholera-endemic areas need to be performed. Protective efficacy that extends for more than a month after vaccination presumably is mediated by direct mucosal immune response which is not assessed in this study. Our results suggest a single dose of OCV in adults in a cholera endemic zone may be sufficient to mediate at least short-term protection.

Strategies for activating TLR4 to improve vaccine effectiveness

“…Mucosal tissues are the main entry portal of many pathogens, including influenza, and the mucosal immune system provides the first line of defense against infections, apart from innate immunity (Akter et al, 2019;Rydell & Sjoholm, 2004). Immunization with Morus alba L. in the vaccinated group increased IgM and IgG more than vaccination only.…”

Gut Microbiota and Development of Vibrio cholerae-Specific Long-Term Memory B Cells in Adults after Whole-Cell Killed Oral Cholera Vaccine

“…Studies of household contacts of patients with cholera indicate that measurable V. cholerae -specific MBC responses to the O-specific polysaccharide (OSP) component of the V. cholerae LPS correlate with protection against infection ( 15 , 16 ). After vaccination with Shanchol, V. cholerae OSP-specific MBC responses are induced in some adults living in cholera areas of endemicity, such as Haiti and Bangladesh ( 17 , 18 ). These responses peak 3 to 6 weeks after vaccination and wane over the period of 1 year ( 17 , 18 ).…”

“…After vaccination with Shanchol, V. cholerae OSP-specific MBC responses are induced in some adults living in cholera areas of endemicity, such as Haiti and Bangladesh ( 17 , 18 ). These responses peak 3 to 6 weeks after vaccination and wane over the period of 1 year ( 17 , 18 ). Depending on the serotype and immunoglobin isotype, 0 to 67% of vaccine recipients develop detectable OSP MBC responses after vaccination ( 17 , 18 ).…”

“…These responses peak 3 to 6 weeks after vaccination and wane over the period of 1 year ( 17 , 18 ). Depending on the serotype and immunoglobin isotype, 0 to 67% of vaccine recipients develop detectable OSP MBC responses after vaccination ( 17 , 18 ).…”

Mucosal immune responses to Vibrio cholerae O-specific polysaccharide in adults following oral vaccination not optimally assessed

“…On August 1, 2019 in the journal PLOS Neglected Tropical Diseases, Akter et al published an in-depth study of the immune responses to Vibrio cholerae O-specific polysaccharide in adults following oral vaccination with a killed whole-cell cholera vaccine in an endemic population (Bangladesh). 1 They state that vaccine responses in serum and mucosal samples to oral cholera vaccination are maximal following the first dose of vaccination, without evident boosting with the second dose. They conclude that these observations suggest that a single dose of oral cholera vaccine may be sufficient to mediate protection in adults in a cholera endemic zone.…”