Delany-Moretlwe, SineadDehbi, Hakim-MoulaySikazwe, IzukanjiKyei, GeorgeKoram, KwadwoDubberke, ErikMwelase, NoluthandoHague, Dominic;Bekker, Linda-GailYun, LindaNel, AnnaleneDu Toit, LeonBiccard, BruceGill, KatherineChipeta, ChikumbutsoMngadi, Kathryn T.Lebina, LimakatsoDassaye, ReshmiAsari, VilleshniFry, Samantha H.Turton, EdwinAhmed, KhatijaKusi, KwadwoAdu-Amankwah, SusanChilengi, RomaChilekwa, Joyce ChinyamaLovat, LaurenceMcGuckin, DermotCaverly, EmiliaPoliti, MarySwan, BenDeSchryver, AnneMckinnon, SherryGupta, AnanyaJones, GemmaFreemantle, NicholasKhader, ShabaanaRees, HelenNetea, Mihai G.Moonesinghe, S. RamaniAvidan, Michael S.2025-11-122025-11-122025-09-16Delany-Moretlwe, S., Dehbi, H.-M., Sikazwe, I., Kyei, G., Koram, K., Dubberke, E., Mwelase, N., Hague, D., Bekker, L.-G., Yun, L., Nel, A., Du Toit, L., Biccard, B., Gill, K., Chipeta, C., Mngadi, K.T., Lebina, L., Dassaye, R., Asari, V., Fry, S.H., Turton, E., Ahmed, K., Kusi, K., Adu-Amankwah, S., Chilengi, R., Chilekwa, J.C., Lovat, L., McGuckin, D., Caverly, E., Politi, M., Swan, B., DeSchryver, A., McKinnon, S., Gupta, A., Jones, G., Freemantle, N., Khader, S., Rees, H., Netea, M.G., Moonesinghe, S.R. & Avidan, M.S. (2025) No evidence of MMR induced trained immunity to prevent SARS COV2: results from a multi- centre RCT. Frontiers in Immunology 16:1588190: 1-9. doi: 10.3389/fimmu.2025.1588190.1664-3224 (online)10.3389/fimmu.2025.1588190http://hdl.handle.net/2263/105243DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.BACKGROUND : Measles-containing vaccines (MCV), by training innate immune cells, are hypothesized to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). METHODS : In this international, double-blind, placebo-controlled trial, we randomly assigned adults, 18 years and older, to receive MCV or saline. The primary outcome was polymerase chain reaction (PCR) confirmed symptomatic COVID-19, up to 60 days after intervention. Secondary outcomes were PCR-confirmed symptomatic COVID-19 and serologically confirmed SARS-CoV-2 infection, up to 150 days after intervention. RESULTS : Of 3411 randomised participants, the modified intention-to-treat population included 1607 in the MCV and 1545 in the saline group. The estimated risk of symptomatic COVID-19 by 60 days was 1.5% in the MCV and 1.2% in the saline group (risk difference, 0.3 percentage points, 95% CI, -0.5 to 1.1; p=0.52). At 150 days, these percentages were 4.1% (65/1585) and 4.1% (64/1544) in the MCV and saline groups, respectively (risk difference, 0.04 percentage points, 95% CI, -1.4 to 1.3; p=0.95). Based on serology results available at 0 and 150 days, 10.6% (100/945) of participants in the MCV and 10.3% (98/951) in the saline group had infection with SARS-CoV-2 over the course of the trial (risk difference, 0.3 percentage points, 95% CI, -2.6 to 3.1; p=0.84). Three patients were hospitalised with COVID-19 disease in the MCV and one in the saline group. CONCLUSIONS : Administering MCVs to stimulate trained immunity did not prevent COVID-19 or SARS-CoV2 infection. Stimulating trained immunity might not be useful for preventing respiratory illness during future pandemics. CLINICAL TRIAL REGISTRATION : https://clinicaltrials.gov/, identifier NCT04333732.en© 2025 Delany-Moretlwe, Dehbi, Sikazwe, Kyei, Koram, Dubberke, Mwelase, Hague, Bekker, Yun, Nel, Toit, Biccard, Gill, Chipeta, Mngadi, Lebina, Dassaye, Asari, Fry, Turton, Ahmed, Kusi, Adu-Amankwah, Chilengi, Chilekwa, Lovat, McGuckin, Caverly, Politi, Swan, DeSchryver, McKinnon, Gupta, Jones, Freemantle, Khader, Rees, Netea, Moonesinghe and Avidan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).Measles-containing vaccines (MCV)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)COVID-19 pandemicCoronavirus disease 2019 (COVID-19)Polymerase chain reaction (PCR)Trained immunityMeaslesMumpsPreventionRubellaArticle