{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:39:02Z","timestamp":1781188742787,"version":"3.54.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cholera is a public health threat in resource-limited settings and is responsible for causing over 3 million cases globally. Mucosal immune responses play an important role in protecting against <jats:italic>Vibrio cholerae<\/jats:italic> infection, a non-invasive mucosal pathogen, yet traditional plasma-based assays are invasive and logistically challenging, particularly during outbreaks in low- and middle-income countries (LMICs). Saliva offers a unique window into mucosal immunity and may serve as a non-invasive alternative for seroprevalence and vaccine immunogenicity studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a cross-sectional antibody profiling study to analyse cholera-specific antibodies in saliva and plasma samples from 74 participants upon presenting to the cholera treatment centres. These were collected from four treatment centres in Lusaka during Zambia\u2019s most severe cholera outbreak in 2024 caused by <jats:italic>Vibrio cholerae<\/jats:italic> O1 Ogawa. Levels of total IgG, IgG1-3, IgM, secretory IgA, and IgA1\u20132 isotypes were used to compare the biomarker profile between the two sample types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Saliva and plasma antibody profiles were comparable, with elevated IgA1 and IgA2 responses to cholera toxin-B (CtxB), sialidase, HlyA, and TcpA in saliva. Broader systemic responses were seen in plasma, including high CtxB-specific IgM, IgA1, and total IgG levels. Notably, biomarkers such as HlyA, Ogawa O-specific polysaccharide (OSP), and sialidase exhibited significant positive correlations between plasma and saliva. Elevated biomarker levels of HlyA, Ogawa O-specific polysaccharide (OSP), and sialidase in people living with HIV\/AIDS (PLWHA) suggested immunological differences that warrant further exploration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrate that saliva is a viable, non-invasive alternative for cholera antibody-based profiling, offering practical advantages in resource-constrained settings. Given its strong correlation with systemic antibody profiles, saliva may be a practical sample for sero-surveillance in resource-limited settings. Future studies should investigate the duration of these salivary responses to further substantiate their use in estimating disease burden and immunity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1641319","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T05:29:45Z","timestamp":1755235785000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Vibrio cholerae-specific antibodies in plasma and saliva in cholera patients during a severe outbreak in Zambia: an antibody profiling approach"],"prefix":"10.3389","volume":"16","author":[{"given":"Charlie C.","family":"Luchen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Ngo\u2019mbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fraser","family":"Liswaniso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Bosomprah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia A.","family":"Zhiteneva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richelle C.","family":"Charles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward T.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biana","family":"Bernshtein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C.","family":"Chisenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"B1","unstructured":"Multi-country outbreak of cholera, External situation report 19\u201318 October 2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008227","article-title":"Identification of cholera hotspots in Zambia: A spatiotemporal analysis of cholera data from 2008 to 2017","volume":"14","author":"Mwaba","year":"2020","journal-title":"PloS Negl Trop Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.11604\/pamj.2024.48.19.43659","article-title":"Multisectoral approach for the control of cholera outbreak - lessons and challenges from Lusaka district - Zambia, October 2023 - February 2024","volume":"48","author":"Kateule","year":"2024","journal-title":"Pan Afr Med J"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy414","article-title":"Cholera: immunity and prospects in vaccine development","volume":"218","author":"Harris","year":"2018","journal-title":"J Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab497","article-title":"Correlates of protection for cholera","volume":"224","author":"Iyer","year":"2021","journal-title":"J Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"6958293","DOI":"10.1155\/2016\/6958293","article-title":"Potential use of salivary markers for longitudinal monitoring of inflammatory immune responses to vaccination","volume":"2016","author":"Lim","year":"2016","journal-title":"Mediators Inflamm"},{"key":"B7","doi-asserted-by":"publisher","first-page":"uxae092","DOI":"10.1093\/cei\/uxae092","article-title":"Diagnostic accuracy of saliva-based testing as a Vibrio cholerae surveillance tool among naturally infected patients","volume":"219","author":"Chisenga","year":"2024","journal-title":"Clin Exp Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.24.2.203-209.1986","article-title":"Saliva, breast milk, and serum antibody responses as indirect measures of intestinal immunity after oral cholera vaccination or natural disease","volume":"24","author":"Jertborn","year":"1986","journal-title":"J Clin Microbiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4808-4814.2003","article-title":"Antigen-specific immunoglobulin A antibodies secreted from circulating B cells are an effective marker for recent local immune responses in patients with cholera: comparison to antibody-secreting cell responses and other immunological markers","volume":"71","author":"Qadri","year":"2003","journal-title":"Infect Immun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007634","article-title":"Induction of systemic, mucosal and memory antibody responses targeting Vibrio cholerae O1 O-specific polysaccharide (OSP) in adults following oral vaccination with an oral killed whole cell cholera vaccine in Bangladesh","volume":"13","author":"Akter","year":"2019","journal-title":"PloS Negl Trop Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12977-017-0380-3","article-title":"Systems serology: profiling vaccine induced humoral immunity against HIV","volume":"14","author":"Chung","year":"2017","journal-title":"Retrovirology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41541-023-00613-1","article-title":"Systems serology-based comparison of antibody effector functions induced by adjuvanted vaccines to guide vaccine design","volume":"8","author":"Loos","year":"2023","journal-title":"NPJ Vaccines"},{"key":"B13","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jim.2018.01.013","article-title":"Optimization and qualification of an Fc Array assay for assessments of antibodies against HIV-1\/SIV","volume":"455","author":"Brown","year":"2018","journal-title":"J Immunol Methods"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(22)00391-3","article-title":"Predicting Vibrio cholerae infection and symptomatic disease: a systems serology study","volume":"4","author":"Wiens","year":"2023","journal-title":"Lancet Microbe"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics."},{"key":"B16","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B Methodol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02463\/full","article-title":"El tor biotype vibrio cholerae activates the caspase-11-independent canonical nlrp3 and pyrin inflammasomes","volume":"10","author":"Mamantopoulos","year":"2019","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011558","article-title":"Vibrio cholerae Hemolysin Is Required for Lethality, Developmental Delay, and Intestinal Vacuolation in Caenorhabditis elegans","volume":"5","author":"Cinar","year":"2010","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.01232-20","article-title":"Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera","volume":"6","author":"Kaisar","year":"2021","journal-title":"mSphere."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.jaci.2009.03.013","article-title":"IVIg contains a broad repertoire of anti-carbohydrate antibodies that is not restricted to the IgG2 subclass","volume":"123","author":"von Gunten","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00562-10","article-title":"Antigen-specific memory B-cell responses in Bangladeshi adults after one- or two-dose oral killed cholera vaccination and comparison with responses in patients with naturally acquired cholera \u25bf","volume":"18","author":"Alam","year":"2011","journal-title":"Clin Vaccine Immunol CVI."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0260552","article-title":"Effect of HIV status and retinol on immunogenicity to oral cholera vaccine in adult population living in an endemic area of Lukanga Swamps, Zambia","volume":"16","author":"Luchen","year":"2021","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00241\/full","article-title":"Compromised mucosal immunity: oral manifestations and systemic inflammation","volume":"8","author":"Heron","year":"2017","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1601-0825.2010.01727.x","article-title":"HIV infection and periodontal diseases: an overview of the post-HAART era","volume":"17","author":"Mataftsi","year":"2011","journal-title":"Oral Dis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.3390\/medicina58091214","article-title":"Oral manifestations associated with HIV\/AIDS patients","volume":"58","author":"Lomel\u00ed-Mart\u00ednez","year":"2022","journal-title":"Medicina (Mex)."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01900-22","article-title":"Identifying recent cholera infections using a multiplex bead serological assay","volume":"13","author":"Jones","year":"2022","journal-title":"mBio."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.01232-20","article-title":"Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera","volume":"6","author":"Kaisar","year":"2021","journal-title":"mSphere."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.12.005","article-title":"Human secretory igM: an elusive player in mucosal immunity","volume":"41","author":"Michaud","year":"2020","journal-title":"Trends Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.04.011","article-title":"Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection","volume":"36","author":"Haney","year":"2018","journal-title":"Vaccine."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007874","article-title":"Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba","volume":"13","author":"Hossain","year":"2019","journal-title":"PloS Negl Trop Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1641319\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T05:29:46Z","timestamp":1755235786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1641319\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":30,"alternative-id":["10.3389\/fimmu.2025.1641319"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1641319","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]},"article-number":"1641319"}}