Immune response of oral cholera vaccine, Shanchol in Bangladeshi recipients

Abstract

Cholera, an acute and severe dehydrating diarrheal disease caused by Vibrio cholerae O1 remains a major public health concern which has significant morbidity and mortality worldwide. Several efforts have been made to develop cholera vaccines that could confer long term protection. T cells play an important role in immunity to cholera and may contribute to the activation of B cells. So, understanding the memory T cell responses is important for optimizing design of oral cholera vaccine or immunization strategies. It had been investigated that immunization with the oral cholera vaccine, Shanchol, induces V. cholerae antigens specific CD4+ and CD8+ memory T cell responses in Bangladeshi adult participants. The study enrolled 45 adult healthy participants and divided them into three groups (In each group n=15) where two groups received double doses of the vaccine (14 days and 30 days apart) and another group received single dose of the vaccine alone. The main objective of the study was to examine V. cholerae antigens, including membrane preparation (MP) and mutant CT (mCT) specific T cell responses by the flow cytometric assay of the specific cell-mediated immune responses in activated whole blood (FASCIA). After vaccination stimulation with MP showed better proliferative CD4+/CD45RO+ and CD8+/CD45RO+ memory T-cell responses than mCT at day 7 compared to baseline in all vaccine cohorts. However, one month after the last dose of the vaccine, the responses were all most diminished over the period of day 90 in all vaccination regimens. Overall a high baseline proliferative CD4+ and CD8+ T cell responses to mCT was found in all vaccinee groups but it did not show increased memory T cell responsiveness significantly to mCT after vaccination. This is because the absence of cholera toxin (CT) and presence of Lipopolysaccharide (LPS) of different V. cholerae strains in the vaccine. Again, V. cholerae O1 Ogawa and Inaba specific vibriocidal antibody responses were also observed maximum at day 7 after administration of one dose of vaccine in all vaccine cohorts. After one month of last dose of the vaccination, the responses started to wane gradually and became vastly reduced at subsequent study days in all vaccination regimens. In contrast the two doses given 30 days apart showed significantly increased responses in comparison to baseline over the period of day 90. These findings suggested that single dose vaccine regimen was as effective as double dose vaccine regimens. So it can be concluded that this early proliferative T cell response is a potent tool that provides help for the generation of subsequent memory B cell responses. However, additional studies are needed to determine whether these early T-cell-mediated events would help to design a more effective vaccine as well as provide long-lasting immunity.