{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:54Z","timestamp":1785437034927,"version":"3.56.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI175214"],"award-info":[{"award-number":["R01AI175214"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI177144"],"award-info":[{"award-number":["R01AI177144"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      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\n                      <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                      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\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      biotypes and serogroups, we found that antibodies raised against a shared epitope (EP #1, IQSQNMTKAAQ) provided partial protection against\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      bacterial adherence\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . 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.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        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\n                        <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                        infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.00350-26","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:02:30Z","timestamp":1777554150000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Vibrio cholerae<\/i>\n                    O1 classical and El Tor toxin-coregulated pilus subunit A (TcpA) epitopes that induce biotype-specific and cross-protective antibodies against bacterial adherence"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-6377","authenticated-orcid":true,"given":"Sai Simha Reddy","family":"Vakamalla","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology, University of Illinois Urbana-Champaign","place":["Urbana, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9338-5119","authenticated-orcid":true,"given":"David A.","family":"Sack","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of International Health, Johns Hopkins University Bloomberg School of Public Health","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-2257","authenticated-orcid":true,"given":"Weiping","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047426m28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology, University of Illinois Urbana-Champaign","place":["Urbana, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003832"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30559-7"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-82-1-101"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2000.62.513"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2012.11-0435"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001145"},{"key":"e_1_3_4_8_2","first-page":"431","article-title":"Cholera annual report 2022","volume":"2022","author":"(WHO) WHO","year":"2022","unstructured":"(WHO) WHO. 2022. 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