{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:03:34Z","timestamp":1789578214102,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Gates Foundation","doi-asserted-by":"publisher","award":["INV-067376"],"award-info":[{"award-number":["INV-067376"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Gates Foundation","doi-asserted-by":"publisher","award":["INV-006888"],"award-info":[{"award-number":["INV-006888"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"award":["INV-067376"],"award-info":[{"award-number":["INV-067376"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-006888"],"award-info":[{"award-number":["INV-006888"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Twenty years after the introduction of rotavirus vaccines, the 15th International Rotavirus Symposium convened researchers, clinicians, immunization program managers, and policymakers to review advances in rotavirus epidemiology, immunology, vaccine development, and implementation. Rotavirus vaccination has contributed to sustained reductions in severe rotavirus hospitalizations and child mortality, yet population-level benefits remain heterogeneous and are constrained by gaps in coverage, supply-related program disruptions, and context-specific vaccine performance. Presenters highlighted evidence from multi-pathogen surveillance confirming that rotavirus remains a leading cause of pediatric diarrhea requiring hospitalization despite widespread vaccine introduction. Accumulating evidence implicates maternally derived antibodies, environmental enteric dysfunction, and early-life microbiome development as contributors to reduced oral vaccine performance in low- and middle-income communities, while recent studies of next-generation vaccine candidates underscore the need for improved correlates of protection and clinically meaningful efficacy endpoints. Collectively, the symposium emphasized that further reductions in rotavirus morbidity and mortality will require strengthening delivery of existing vaccines\u2014including improving coverage, minimizing supply interruptions, and reaching zero-dose and under-immunized children\u2014while sustaining surveillance and investing in integrated enteric disease prevention and next-generation vaccines to optimize protection in high-burden settings.<\/jats:p>","DOI":"10.3390\/vaccines14090815","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:07:29Z","timestamp":1789574849000},"page":"815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rotavirus Vaccines at 20 Years: Success, Challenges, and the Road Ahead"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1020-232X","authenticated-orcid":false,"given":"Alice S.","family":"Carter","sequence":"first","affiliation":[{"name":"Vaccine Epidemiology, Global Immunization, Sabin Vaccine Institute, Washington, DC 20006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4946-037X","authenticated-orcid":false,"given":"Duncan","family":"Steele","sequence":"additional","affiliation":[{"name":"Enterics, Diagnostics, Genomics & Epidemiology, Gates Foundation, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathuram","family":"Santosham","sequence":"additional","affiliation":[{"name":"Department of International Health and Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5893-3725","authenticated-orcid":false,"given":"Michelle J.","family":"Groome","sequence":"additional","affiliation":[{"name":"South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise O.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Vaccine Epidemiology, Global Immunization, Sabin Vaccine Institute, Washington, DC 20006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/infdis\/jiaa081","article-title":"Global Impact of Rotavirus Vaccination on Diarrhea Hospitalizations and Deaths Among Children <5 Years Old: 2006\u20132019","volume":"222","author":"Burnett","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_2","unstructured":"(2026, June 23). Rotavirus Vaccine | ViewHub. Available online: https:\/\/view-hub.org\/vaccine\/rota."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/S1473-3099(24)00158-0","article-title":"Global burden associated with 85 pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"24","author":"Naghavi","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e919","DOI":"10.1016\/S2214-109X(24)00078-0","article-title":"Estimated global and regional causes of deaths from diarrhoea in children younger than 5 years during 2000-21: A systematic review and Bayesian multinomial analysis","volume":"12","author":"Black","year":"2024","journal-title":"Lancet Glob. Health"},{"key":"ref_5","unstructured":"(2026, April 07). Rotavirus Vaccines: WHO Position Paper\u2014July 2021. Available online: https:\/\/www.who.int\/publications\/i\/item\/WHO-WER9628."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7119","DOI":"10.1016\/j.vaccine.2018.06.026","article-title":"Impact of Rotavirus Vaccines in Sub-Saharan African Countries","volume":"36","author":"Mwenda","year":"2018","journal-title":"Vaccine"},{"key":"ref_7","unstructured":"Weldegebriel, G. (October, January 30). Trends in rotavirus positivity following vaccine introduction in East and Southern Africa, 2010\u20132023. Proceedings of the 15th International Rotavirus Symposium, Cape Town, South Africa. Available online: https:\/\/www.sabin.org\/app\/uploads\/2025\/10\/Goitom-Weldegebriel-IRS15.pdf."},{"key":"ref_8","unstructured":"Ola, F. (October, January 30). Impact of Rotavirus Vaccine on Childhood Rotavirus Hospitalisations in Nigeria: Evidence from the First Two Years After Rotavirus Vaccine Introduction. Proceedings of the 15th International Rotavirus Symposium, Cape Town, South Africa. Available online: https:\/\/www.sabin.org\/app\/uploads\/2025\/10\/Francis-Ola-IRS15.pdf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12985-026-03126-0","article-title":"Molecular epidemiology of rotavirus causing diarrhea among under-five children after the introduction of rotavirus vaccines, Rotavac and Rotasiil, into the national immunization program of India","volume":"23","author":"Varghese","year":"2026","journal-title":"Virol. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1001\/jamapediatrics.2018.1960","article-title":"Rotavirus Vaccination and the Global Burden of Rotavirus Diarrhea Among Children Younger Than 5 Years","volume":"172","author":"Troeger","year":"2018","journal-title":"JAMA Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s41182-026-00917-7","article-title":"Prevalence and molecular epidemiology of rotavirus gastroenteritis among children in Nairobi\u2019s urban informal settlements following introduction of the Rotavac\u00ae vaccine","volume":"54","author":"Mbithi","year":"2026","journal-title":"Trop. Med. Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127944","DOI":"10.1016\/j.vaccine.2025.127944","article-title":"Rotasiil vaccine effectiveness against rotavirus-associated hospitalizations in the Democratic Republic of the Congo: Comparison of multivariate logistic regression and inverse probability treatment weighting methods in a test-negative design","volume":"68","author":"Lungayo","year":"2025","journal-title":"Vaccine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"126726","DOI":"10.1016\/j.vaccine.2025.126726","article-title":"Effectiveness of monovalent rotavirus vaccine against hospital-attended rotavirus gastroenteritis among children in Uganda","volume":"48","author":"Aanyu","year":"2025","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"128555","DOI":"10.1016\/j.vaccine.2026.128555","article-title":"Effectiveness of monovalent rotavirus vaccine among young children in Pakistan: A test-negative case-control evaluation","volume":"81","author":"Ali","year":"2026","journal-title":"Vaccine"},{"key":"ref_15","unstructured":"Thobari, J.A. (October, January 30). Effectiveness of Rotavac Against Severe Rotavirus Gastroenteritis in Indonesian Children During Early Vaccine Introduction Phase. Proceedings of the 15th International Rotavirus Symposium, Cape Town, South Africa. Available online: https:\/\/www.sabin.org\/app\/uploads\/2025\/10\/Jarir-at-Thobari-IRS15.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e009548","DOI":"10.1136\/bmjgh-2022-009548","article-title":"Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: Findings from the Global Pediatric Diarrhea Surveillance network","volume":"7","author":"Cohen","year":"2022","journal-title":"BMJ Glob. Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1047","DOI":"10.1093\/cid\/ciac561","article-title":"Risk Factors for Mortality Among Children Younger Than Age 5 Years with Severe Diarrhea in Low- and Middle-income Countries: Findings from the World Health Organization-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks","volume":"76","author":"Hartman","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1093\/cid\/ciac948","article-title":"Stunting Following Moderate-to-Severe Diarrhea Among Children Aged <5 Years in Africa Before and After Rotavirus Vaccine Introduction: A Comparison of the Global Enteric Multicenter Study and the Vaccine Impact on Diarrhea in Africa (VIDA) Study","volume":"76","author":"Nasrin","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105818","DOI":"10.1016\/j.meegid.2025.105818","article-title":"Whole genome characterisation of DS-1-like G8P [4] rotavirus A strains circulating in South Africa between 2009 and 2021 reveals endemic sub-lineages and evidence of radical epitope changes","volume":"134","author":"Shange","year":"2025","journal-title":"Infect. Genet. Evol."},{"key":"ref_20","unstructured":"Makekeng, P. (October, January 30). Acute gastroenteritis mortality among children under 5 years in Soweto, South Africa: Insights from minimally invasive tissue sampling, 2017\u20132025. Proceedings of the 15th International Rotavirus Symposium, Cape Town, South Africa. Available online: https:\/\/www.sabin.org\/app\/uploads\/2025\/10\/Palesa-Makekeng-IRS15.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S1473-3099(26)00136-2","article-title":"Post-mortem characterisation of pathogen-specific causes of infection-related deaths in African and south Asian neonates: A prospective, observational, multicentre study","volume":"26","author":"Alam","year":"2026","journal-title":"Lancet Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/infdis\/jiae597","article-title":"Rotavirus vaccine effectiveness stratified by national-level characteristics: An introduction to the 24-country MNSSTER-V Project, 2007\u20132023","volume":"232","author":"Burnett","year":"2025","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1080\/21645515.2020.1844525","article-title":"Update on rotavirus vaccine underperformance in low- to middle-income countries and next-generation vaccines","volume":"17","author":"Lee","year":"2021","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/cid\/civ828","article-title":"Prevaccination Rotavirus Serum IgG and IgA Are Associated with Lower Immunogenicity of Live, Oral Human Rotavirus Vaccine in South African Infants","volume":"62","author":"Moon","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7288","DOI":"10.1038\/s41467-021-27074-1","article-title":"Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants","volume":"12","author":"Parker","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Otero, C.E., Langel, S.N., Blasi, M., and Permar, S.R. (2020). Maternal antibody interference contributes to reduced rotavirus vaccine efficacy in developing countries. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1009010"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6343","DOI":"10.1038\/s44318-025-00582-2","article-title":"Mechanisms of maternal antibody interference with rotavirus vaccination","volume":"44","author":"Chandler","year":"2025","journal-title":"EMBO J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mandolo, J., Mulira, L., Moyo, M., Mvula, M., Mtonga, F., Henrion, M.Y.R., Wotcheni, W., Cunliffe, N.A., Barnes, K.G., and Jambo, K.C. (2025). Maternal-infant rotavirus-specific antibody kinetics to inform timing of vaccine boosting in Malawi: An observational study. PLoS Med., 22.","DOI":"10.1371\/journal.pmed.1004734"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.chom.2018.07.005","article-title":"Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial","volume":"24","author":"Harris","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.chom.2021.12.002","article-title":"Enteric virome negatively affects seroconversion following oral rotavirus vaccination in a longitudinally sampled cohort of Ghanaian infants","volume":"30","author":"Kim","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_31","unstructured":"Wirusanti, N.I., van Schajik, Y., Kim, J., Frempong, J.F., Simkhada, N., Fisher, S., Pucci, N., Piedade, G.J., Luchen, C.C., and Chibuye, M. (2025). Microbiota-derived indole metabolites inhibit rotavirus infection in vitro and in vivo and in human infants. bioRxiv."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Rubinstein, R.J., Vielot, N.A., Edwards, J., Reyes, Y., Gonz\u00e1lez, F., Toval-Ru\u00edz, C., Guti\u00e9rrez, L., Mijatovic-Rustempasic, S., Vilchez, S., and Sandler, R.S. (2025). Human milk oligosaccharides, oral rotavirus vaccine seroconversion, and rotavirus gastroenteritis risk in a vaccinated birth cohort. medRxiv.","DOI":"10.64898\/2025.12.04.25341660"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Laban, N.M., Goodier, M.R., Bosomprah, S., Simuyandi, M., Chisenga, C., Chilyabanyama, O.N., and Chilengi, R. (2022). T-Cell Responses after Rotavirus Infection or Vaccination in Children: A Systematic Review. Viruses, 14.","DOI":"10.3390\/v14030459"},{"key":"ref_34","unstructured":"Laban, N.M. (2024). Antibody and T-Cell Responses in Rotavirus Vaccinated Zambian Infants: Impact of Human Cytomegalovirus Infection. [Ph.D. Thesis, London School of Hygiene & Tropical Medicine]. Available online: https:\/\/researchonline.lshtm.ac.uk\/id\/eprint\/4674820\/1\/2024_ITD_PhD_Laban_N.pdf."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S1473-3099(20)30001-3","article-title":"Safety and immunogenicity of a parenteral trivalent P2-VP8 subunit rotavirus vaccine: A multisite, randomised, double-blind, placebo-controlled trial","volume":"20","author":"Groome","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"128019","DOI":"10.1016\/j.vaccine.2025.128019","article-title":"Safety, immunogenicity, and relative efficacy of a parenteral trivalent rotavirus subunit vaccine candidate (TV P2-VP8) in healthy Ghanaian, Malawian, and Zambian infants","volume":"70","author":"Tewari","year":"2026","journal-title":"Vaccine"},{"key":"ref_37","unstructured":"Lemire, G. (October, January 30). Preliminary Immune Correlates of Risk Analysis from the trivalent P2-VP8 Rotavirus Vaccine Trial. Proceedings of the 15th International Rotavirus Symposium, Cape Town, South Africa. Available online: https:\/\/www.sabin.org\/app\/uploads\/2025\/10\/Gabrielle-Lemire-IRS15.pdf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S1473-3099(21)00473-4","article-title":"Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: A randomised, double-blind, four-arm parallel group dose-ranging study","volume":"22","author":"Witte","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Morgan, B., Lyons, E.A., Handley, A., Bogdanovic-Sakran, N., Pavlic, D., Witte, D., Mandolo, J., Turner, A., Jere, K.C., and Justice, F. (2024). Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi. Viruses, 16.","DOI":"10.3390\/v16091488"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Temprana, C.F., Arg\u00fcelles, M.H., Gutierrez, N.M., Barril, P.A., Esteban, L.E., Silvestre, D., Mandile, M.G., Glikmann, G., and Castello, A.A. (2018). Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203700"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"126768","DOI":"10.1016\/j.vaccine.2025.126768","article-title":"A decade of rotavirus vaccination in the World Health Organization African Region: An in-depth analysis of vaccine coverage from 2012 to 2023","volume":"48","author":"Mwenda","year":"2025","journal-title":"Vaccine"},{"key":"ref_42","unstructured":"(2026, June 26). Immunization Data. WHO Immunization Data Portal\u2014Detail Page. Available online: https:\/\/immunizationdata.who.int\/global\/wiise-detail-page."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Mandomando, I., Messa, A., Biey, J.N.M., Paluku, G., Mumba, M., and Mwenda, J.M. (2023). Lessons Learned and Future Perspectives for Rotavirus Vaccines Switch in the World Health Organization, Regional Office for Africa. Vaccines, 11.","DOI":"10.3390\/vaccines11040788"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"127012","DOI":"10.1016\/j.vaccine.2025.127012","article-title":"Challenges and lessons learned during the switching of rotavirus vaccine from Rotarix to Rotavac in Zambia","volume":"55","author":"Mpabalwani","year":"2025","journal-title":"Vaccine"},{"key":"ref_45","unstructured":"Rennert, W. (October, January 30). The Epidemiology of Rotavirus Gastroenteritis in Palestine 2014\u20132025. Proceedings of the 15th International Rotavirus Symposium, Cape Town, South Africa. Available online: https:\/\/www.sabin.org\/app\/uploads\/2025\/10\/Wolfgang-Rennert-IRS15.pdf."},{"key":"ref_46","unstructured":"Umar, M. (October, January 30). Bridging Access and Trust: A Community-Driven Strategy to Strengthen Rotavirus Vaccine Uptake in Refugee-Hosting Districts of South Western Uganda. Proceedings of the 15th International Rotavirus Symposium, Cape Town, South Africa. Available online: https:\/\/www.sabin.org\/app\/uploads\/2025\/10\/Muhumuza-Umar-IRS15.pdf."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"128010","DOI":"10.1016\/j.vaccine.2025.128010","article-title":"An impact and cost-effectiveness analysis of rotavirus vaccine introduction in Egypt","volume":"69","author":"Shaheen","year":"2026","journal-title":"Vaccine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"126478","DOI":"10.1016\/j.vaccine.2024.126478","article-title":"Cost effectiveness analysis of rotavirus vaccination in Indonesia","volume":"43","author":"Thobari","year":"2025","journal-title":"Vaccine"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/815\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:22:59Z","timestamp":1789575779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["vaccines14090815"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14090815","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}