Systemic, Mucosal, and Memory Immune Responses following Cholera

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.

Identifying recent cholera infections using a multiplex bead serological assay

“…Based on a review of the published literature on immune responses to V. cholerae infection [30][31][32], we selected seven known cholera-related antigens to investigate with a multiplex bead assay. These included O1 serogroup Ogawa serotype O-specific polysaccharide (OSP, part of the LPS), O1 serogroup Inaba serotype OSP, cholera toxin B subunit (CT-B), cholera toxin holotoxin (CT-H), Toxin co-regulated pilus subunit A (TcpA), V. cholerae cytolysin (VCC) (also known as hemolysin A), and V. cholerae sialidase.…”

Long-Term Kinetics of Serological Antibodies against Vibrio cholerae Following a Clinical Cholera Case: A Systematic Review and Meta-Analysis

“…Furthermore, the correlation of vibriocidal antibody titers with protection remains debatable. Cholera vaccines that induce vibriocidal antibodies similar to those generated by wild-type infections have not clearly been clinically effective [ 28 , 53 ]. However, vaccine-induced vibriocidal seroconversion is associated with protection [ 51 ].…”

“…They more efficiently enter the gut lumen and prevent V. cholerae from adhering and colonizing to the gut and might result in long-term protective immunity in individuals recovering from cholera [ 27 ]. Furthermore, clinical cholera leads to the development of anti-LPS antibodies with avidity indices that correlate with memory B cell responses; thus, protection against cholera is currently hypothesized to be mediated by anti-LPS antibodies and more specifically by antibodies for O-specific polysaccharides [ 28 ]. Indeed, consistent associations had been reported between OSP-specific IgA and IgG antibodies and a lower risk of infection by V. cholerae in household contacts of patients with cholera [ 63 ].…”

“…Furthermore, vibriocidal responses are also associated with protection against V. cholerae infection. Previous studies have demonstrated that anti-CTB and anti-LPS antibodies and vibriocidal antibody titers sharply increase immediately (within 7–30 days) after symptom onset and rapidly decrease within 360 days [ 28 , 29 ]. Following clinical cholera, serum anti-CTB and anti-LPS antibodies provide a better indication of immune protection than the vibriocidal antibody [ 30 ].…”

“…Following clinical cholera, serum anti-CTB and anti-LPS antibodies provide a better indication of immune protection than the vibriocidal antibody [ 30 ]. Several cohort studies reported the expression of antibodies following cholera, and several reviews on this topic have been published [ 10 , 25 , 28 , 31 ]; however, none of them have carried out a meta-analysis, i.e., the evidence has not been quantitatively synthesized yet. Therefore, we conducted a systematic review and meta-analysis to evaluate how antibody levels change quantitatively over time after clinical cholera.…”