{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:22:07Z","timestamp":1791404527780,"version":"4.3.3"},"reference-count":109,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill &amp; Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1164384"],"award-info":[{"award-number":["OPP1164384"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["201945\/Z\/16\/Z"],"award-info":[{"award-number":["201945\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["PDF\u20102018\u201011\u2010ST2\u2010006"],"award-info":[{"award-number":["PDF\u20102018\u201011\u2010ST2\u2010006"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children &lt;5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Gu\u00e9rin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.<\/jats:p>","DOI":"10.3390\/vaccines10030418","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T20:19:10Z","timestamp":1646943550000},"page":"418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Leveraging Beneficial Off-Target Effects of Live-Attenuated Rotavirus Vaccines"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6215-270X","authenticated-orcid":false,"given":"Prisca","family":"Benedicto-Matambo","sequence":"first","affiliation":[{"name":"Virology Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 312225, Malawi"},{"name":"Centre for Global Vaccine Research, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK"},{"name":"Department of Medical Laboratory Sciences, Faculty of Biomedical Sciences and Health Professions, College of Medicine, Kamuzu University of Health Sciences, Blantyre 312225, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5452-6601","authenticated-orcid":false,"given":"Julie E.","family":"Bines","sequence":"additional","affiliation":[{"name":"Enteric Diseases Group, Murdoch Children\u2019s Research Institute, Department of Gastroenterology and Clinical Nutrition, Royal Children\u2019s Hospital and Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8585-7948","authenticated-orcid":false,"given":"Chikondi","family":"Malamba-Banda","sequence":"additional","affiliation":[{"name":"Virology Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 312225, Malawi"},{"name":"Centre for Global Vaccine Research, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK"},{"name":"Department of Medical Laboratory Sciences, Faculty of Biomedical Sciences and Health Professions, College of Medicine, Kamuzu University of Health Sciences, Blantyre 312225, Malawi"},{"name":"Department of Biological Sciences, Academy of Medical Sciences, Malawi University of Science and Technology, Blantyre 312225, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac T.","family":"Shawa","sequence":"additional","affiliation":[{"name":"Virology Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 312225, Malawi"},{"name":"Department of Medical Laboratory Sciences, Faculty of Biomedical Sciences and Health Professions, College of Medicine, Kamuzu University of Health Sciences, Blantyre 312225, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8291-4388","authenticated-orcid":false,"given":"Kayla","family":"Barnes","sequence":"additional","affiliation":[{"name":"Virology Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 312225, Malawi"},{"name":"Harvard School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0841-7586","authenticated-orcid":false,"given":"Arox W.","family":"Kamng\u2019ona","sequence":"additional","affiliation":[{"name":"Virology Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 312225, Malawi"},{"name":"Department of Biomedical Sciences, Faculty of Biomedical Sciences and Health Profession, College of Medicine, Kamuzu University of Health Sciences, Blantyre 312225, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9770-0163","authenticated-orcid":false,"given":"Daniel","family":"Hungerford","sequence":"additional","affiliation":[{"name":"Centre for Global Vaccine Research, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK"},{"name":"NIHR Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-2210","authenticated-orcid":false,"given":"Kondwani C.","family":"Jambo","sequence":"additional","affiliation":[{"name":"Virology Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 312225, Malawi"},{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5816-6423","authenticated-orcid":false,"given":"Miren","family":"Iturriza-Gomara","sequence":"additional","affiliation":[{"name":"Centre for Global Vaccine Research, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK"},{"name":"NIHR Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, Liverpool L69 7BE, UK"},{"name":"Centre for Vaccine Innovation and Access, Program for Appropriate Technology in Health (PATH), 1218 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel A.","family":"Cunliffe","sequence":"additional","affiliation":[{"name":"Centre for Global Vaccine Research, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK"},{"name":"NIHR Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1575-1953","authenticated-orcid":false,"given":"Katie L.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Tasmania, Hobart, TAS 7005, Australia"},{"name":"School of Health and Biomedical Science, Royal Melbourne Institute of Technology (RMIT), Bundoora, VIC 3083, Australia"},{"name":"Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3376-8529","authenticated-orcid":false,"given":"Khuzwayo C.","family":"Jere","sequence":"additional","affiliation":[{"name":"Virology Research Group, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 312225, Malawi"},{"name":"Centre for Global Vaccine Research, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK"},{"name":"Department of Medical Laboratory Sciences, Faculty of Biomedical Sciences and Health Professions, College of Medicine, Kamuzu University of Health Sciences, Blantyre 312225, Malawi"},{"name":"NIHR Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, Liverpool L69 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","unstructured":"WHO (2021, October 11). 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