Work

Vibrio cholerae O1 classical and El Tor toxin-coregulated pilus subunit A (TcpA) epitopes that induce biotype-specific and cross-protective antibodies against bacterial adherence

Year: 2026

Type: article

Abstract: ABSTRACT The persistent and deadly cholera remains a significant burden on global health. Current countermeasures are inadequate against cholera. Toxin-coregulated pilin (TCP) has long been a target for understanding the biogenesis of Vibrio cholerae infection and for developing subunit vaccines against cholera. In this study, we examined TcpA B-cell epitopes of the O1 classical and El Tor biotypes, as well as the O139 serogroup, for functionality, potential biogenesis, and vaccine application. By empirically mapping TcpA functional epitopes across V. cholerae biotypes and serogroups, we found that antibodies raised against a shared epitope (EP #1, IQSQNMTKAAQ) provided partial protection against V. cholerae bacterial adherence in vitro . Data also showed that classical biotype TcpA epitope #6, ASKNLDLTNITHVE, is more effective in inducing functional antibodies against adherence of the classical biotype, but not against the El Tor biotype. Similarly, El Tor biotype TcpA epitopes #4 (FAAVADLGDFETSV) and #6 (GSANLNLTNITHVE) are effective in inducing functional antibodies against the adherence of El Tor biotype and O139 serogroup, but not against the classical biotype. This decodes early observations of a lack of cross-protection from TcpA-derived immunity. Interestingly, combined immunity raised against the classical epitope #6 and the El Tor epitope #6 (or #4) effectively protected against adherence from both biotypes. These results reveal the mechanism underlying the lack of protective immunity conferred by biotype-specific TcpA and indicate a combined epitope immunity for protection across biotypes and serogroups, providing a better understanding of TcpA immunity, perhaps its biogenesis, and guiding the development of cholera vaccines. IMPORTANCE Current countermeasures are inadequate against cholera, a disease that remains a significant global health burden. Oral cholera vaccines (OCVs) prequalified by the World Health Organization (WHO) are serogroup-specific. In addition to the supply shortage, these whole-cell vaccines provide limited protection to children under 5 years of age in endemic countries, the most vulnerable population to cholera, urgently calling for more effective prevention strategies. By examining functional immunity raised against shared and biotype-specific TcpA epitopes, this study revealed the mechanism underlying why TCP-related immunity from the O1 classical biotype does not extend protection to the O1 El Tor biotype. The current study also showed that a combined biotype-epitope immunity provides cross-protection against O1 El Tor and classical biotypes, as well as against the O139 serogroup, potentially paving the way for the development of a cross-protective vaccine against Vibrio cholerae infection.

Source: Applied and Environmental Microbiology

DOI: 10.1128/aem.00350-26

Authors: Sai Simha Reddy Vakamalla, David A. Sack, Weiping Zhang

Institutions: University of Illinois Urbana-Champaign, Johns Hopkins University

Language: English

Topic: Vibrio bacteria research studies

Subfield: Endocrinology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: National Institutes of Health, National Institute of Allergy and Infectious Diseases