{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:26:08Z","timestamp":1783416368220,"version":"3.54.6"},"update-to":[{"DOI":"10.12688\/f1000research.164227.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000}},{"DOI":"10.12688\/f1000research.164227.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000}},{"DOI":"10.12688\/f1000research.164227.3","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000}}],"reference-count":67,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns5:p>Background Malnutrition impairs immune function and vaccine responses, particularly in low-income settings. This can lead to reduced seroconversion rates and compromised herd immunity in children. Nutritional interventions have been proposed to enhance vaccine immunogenicity, yet evidence remains scattered and context specific. Objective This systematic review assesses the impact of nutritional interventions\u2014especially vitamin A, zinc supplementation, and protein-energy rehabilitation\u2014on serological responses to routine childhood vaccines among malnourished children in low- and middle-income countries. Methods Following PRISMA guidelines, we searched PubMed, Embase, Cochrane Library, and WHO Global Health Library for studies published between 2000 and 2024. Eligible studies included randomized trials, cohort studies, and systematic reviews reporting on nutritional supplementation and vaccine seroconversion outcomes in malnourished children. Narrative reviews and retracted articles (e.g., Chandra RK) were excluded. Results From 3,245 records, 29 studies met the inclusion criteria. Vitamin A supplementation improved measles vaccine seroconversion by 35%, especially among deficient children. Zinc enhanced responses to oral vaccines (rotavirus and OPV) by 20%. Protein-energy rehabilitation significantly increased seroconversion rates for BCG and measles vaccines, particularly in children recovering from severe acute malnutrition. Evidence for iron supplementation and inactivated vaccines remained inconsistent. Conclusion Nutritional interventions can improve vaccine immunogenicity among malnourished children. Vaccination should not be delayed in malnourished children; instead, integrated strategies combining immunization and nutrition services should be prioritized to address immunity gaps in vulnerable populations.<\/ns5:p>","DOI":"10.12688\/f1000research.164227.4","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T14:15:07Z","timestamp":1757600107000},"page":"507","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Micronutrient and protein-energy supplementation enhance vaccine responses in undernourished children: Evidence from a systematic review"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-877X","authenticated-orcid":false,"given":"Guillaume","family":"Ngoie Mwamba","sequence":"first","affiliation":[{"name":"Department of Public Health Kamina 00243 Faculty of Medicine, University of Kamina, Kamina, DRC"},{"name":"Expanded Program on Immunization Kinshasa 00243 Ministry of Health, Kinshasa, DRC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-654X","authenticated-orcid":false,"given":"Michel","family":"Kabamba Nzaji","sequence":"additional","affiliation":[{"name":"Department of Public Health Kamina 00243 Faculty of Medicine, University of Kamina, Kamina, DRC"},{"name":"Expanded Program on Immunization Kinshasa 00243 Ministry of Health, Kinshasa, DRC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Luboya Numbi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Lubumbashi 00243 University of Lubumbashi, Lubumbashi, DRC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mala","family":"Ali Mapatano","sequence":"additional","affiliation":[{"name":"Department of Nutrition Kinshasa 00243 School of Public Health, University of Kinshasa, Kinshasa, DRC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul-Samson","family":"Lusamba Dikassa","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Kinshasa 00243 School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"109-128","DOI":"10.54963\/ti.v9i1.1010","article-title":"Global trends in childhood immunization research: A bibliometric analysis of publications from 1974 to 2025.","volume":"9","author":"J Noya","year":"2025","journal-title":"Trends Immunother."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1-23","DOI":"10.3389\/fnut.2022.1082500","article-title":"The relationship between nutrition and the immune system.","volume":"9","author":"C Munteanu","year":"2022","journal-title":"Front. 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In: F1000Research. Version 3.0.","author":"G Mwamba","year":"2025","journal-title":"Zenodo."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-507\/v4\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-507\/v4\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-507\/v4\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:04:08Z","timestamp":1783415048000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-507\/v4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":67,"URL":"https:\/\/doi.org\/10.12688\/f1000research.164227.4","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.164227.3","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.164227.2","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.164227.1","asserted-by":"subject"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-507\/v4#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.185041.r399142, Eknath D. Ahire, MET's Institute of Pharmacy, Nashik, 08 Aug 2025, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/14-507\/v3#referee-response-399142","order":0,"name":"referee-response-399142","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.185041.r399143, Philip C Calder, University of Southampton, Southampton, England, 08 Aug 2025, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/14-507\/v3#referee-response-399143","order":1,"name":"referee-response-399143","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.185041.r401076, Maren Johanne  Heilskov Rytter, Slagelse Hospital, Slagelse, 08 Aug 2025, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/14-507\/v3#referee-response-401076","order":2,"name":"referee-response-401076","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Guillaume NGOIE MWAMBA<\/b>; \n<i>Posted: 07 Sep 2025<\/i>; \n<b>Notes to Reviewers \u2013 Response to Dr. Maren Johanne Heilskov Rytter<\/b>  Manuscript title: Micronutrient and protein-energy supplementation enhances vaccine responses in undernourished children: Evidence from a systematic review Version: 3 \u2192 4 Reviewer: Dr. Maren Johanne Heilskov Rytter, Slagelse Hospital, Denmark General Note We sincerely thank the reviewer for the constructive and clinically insightful feedback. We have substantially revised the manuscript to address all concerns. Below is our detailed point-by-point response.  \n<b>Inclusion of narrative reviews.<\/b>  Reviewer&nbsp;comment: Most of the included articles are narrative reviews and do not fit the eligibility criteria. Response: All narrative reviews were removed. The revised dataset now contains only randomized controlled trials, cohort, and observational studies (29 in total). The PRISMA flow diagram, Abstract, Methods, and Results have been updated accordingly.  \n<b>Scientific rigor in the evidence base<\/b>  Reviewer comment: The manuscript does not reliably address the subject in a scientifically sound way. Response: The Results were rebuilt to focus exclusively on primary evidence. Table 1 (Excluded studies), Table 2 (Key findings), and Table 3 (GRADE summary) were added to transparently present study-level data and certainty of evidence.  \n<b>Confounding in observational studies<\/b>  Reviewer comment: Associations may be confounded by acute infection; biomarkers are acute-phase reactants. Response: The Discussion and Limitations were revised to highlight confounding by infection and the acute-phase behavior of biomarkers such as ferritin, zinc, and vitamin D.  \n<b>Fraudulent studies (Chandra RK)<\/b>  Reviewer comment: Studies by Chandra RK must be excluded. Response: All studies by Chandra RK were excluded. This is clearly stated in the Methods and shown in the PRISMA diagram under 'other reasons'.  \n<b>Conclusion on sequencing vaccination<\/b>  Reviewer comment: The statement suggesting nutritional rehabilitation before vaccination is potentially harmful. Response: The Conclusion was rewritten to emphasize that vaccination should never be delayed in malnourished children. Immunization and nutrition support should be delivered concurrently.  \n<b>Methods detail (PRISMA 2020 alignment)<\/b>  Reviewer comment: The methodology is insufficiently detailed for replication. Response: The Methods were expanded to include eligibility criteria, search strategy, dual screening, risk-of-bias assessment, and reasons for excluding reviews. A PRISMA 2020 flow diagram is now included.  \n<b>Statistical analysis and meta-analysis<\/b>  Reviewer comment: Statistical validation is required; a meta-analysis should be attempted, or reasons given for not conducting one. Response: A statistician reviewed the dataset. Owing to high heterogeneity across interventions, outcomes, and study designs, a global meta-analysis was not feasible. However, a targeted meta-analysis of vitamin A and measles seroconversion (8 RCTs) was performed. Other outcomes were synthesized narratively using the SWiM framework.  \n<b>Publication years of included trials<\/b>  Reviewer comment: Several included studies are old. Response: Although our initial cutoff was 2000, we retained select pre-2000 trials (e.g., on protein-energy supplementation) that provided unique primary data. Their inclusion is justified in the Methods, and they were critically appraised for risk of bias and interpreted with caution.","URL":"https:\/\/f1000research.com\/articles\/14-507\/v4#referee-comment-14521","order":3,"name":"referee-comment-14521","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}