Systemic, Mucosal, and Memory Immune Responses following Cholera.

Edward T Ryan,Firdausi Qadri,Ashraful Islam Khan,Owen Jensen,Jason B Harris,Stephen B Calderwood,Ana A Weil,Taufiqur Rahman Bhuiyan,Daniel T Leung,Fahima Chowdhury,Regina C Larocque,Richelle C Charles

doi:10.3390/tropicalmed6040192

Abstract

Vibrio cholerae O1, the major causative agent of cholera, remains a significant public health threat. Although there are available vaccines for cholera, the protection provided by killed whole-cell cholera vaccines in young children is poor. An obstacle to the development of improved cholera vaccines is the need for a better understanding of the primary mechanisms of cholera immunity and identification of improved correlates of protection. Considerable progress has been made over the last decade in understanding the adaptive and innate immune responses to cholera disease as well as V. cholerae infection. This review will assess what is currently known about the systemic, mucosal, memory, and innate immune responses to clinical cholera, as well as recent advances in our understanding of the mechanisms and correlates of protection against V. cholerae O1 infection.

Highlights

Cholera is a severe dehydrating disease of humans caused by Vibrio cholerae serogroup O1 and O139
Before O-specific polysaccharide (OSP) became available as a reagent for use in immunologic assays, a body of evidence showed that LPS responses occur following cholera and vaccination in both children and adults, and that these responses correlated with protection against cholera, including in young children [12,13,14,15]
Individuals with cholera are protected for a period well beyond when the serum vibriocidal antibody, circulating antigen-specific plasmablasts, and serum antibody to specific cholera antigens have disappeared or waned in the circulation, suggesting that longerterm protection may depend on anamnestic responses mediated by immunologic memory following primary infection

Summary

Introduction

Cholera is a severe dehydrating disease of humans caused by Vibrio cholerae serogroup O1 and O139. Before OSP became available as a reagent for use in immunologic assays, a body of evidence showed that LPS responses (plasma, mucosal and memory) occur following cholera and vaccination in both children and adults, and that these responses correlated with protection against cholera, including in young children [12,13,14,15]. Anti-OSP/LPS IgG, IgA and IgM responses following immunization of children in Bangladesh with killed oral cholera vaccines are significantly lower than those induced following clinical disease in age-matched patients, including the absence of anti-LPS memory responses in vaccinees despite induction of vibriocidal responses [15,16,18]. This effect requires at least two-point binding of OSP-specific antibodies [21,22,23,24,25,26]

Protein Antigens

Memory B-Cells

Innate Immune Responses to Cholera

Interaction between Microbiota and Cholera Immunity

Findings

Conclusions