Abstract Background COVID-19 vaccine booster doses counteract waning immunity and vaccine escape by emerging variants. We evaluated long-term immunogenicity and safety of fractional and standard BNT162b2 vaccine booster doses in Mongolia. Methods In this randomised, controlled, non-inferiority trial, adults primed with two doses of ChAdOx1-S, BBIBP-CorV, or Gam-COVID-Vac were randomised (1:1) to receive a 15μg (fractional dose) or 30μg (standard-dose) BNT162b2 booster. Geometric mean ratios (GMR) of IgG and surrogate virus neutralising test (sVNT) levels (Wuhan-Hu-1 and Omicron B.1.1.529) were compared over 12 months. SARS-CoV-2 infections, adverse and serious adverse events (SAEs) were documented. ClinicalTrials.gov Identifier: NCT05265065. Results Of 601 participants randomised between May 27th and September 30th, 2022, 2 (0.3%) were lost to follow-up and 19 (3.2%) withdrew by 12 months. IgG levels declined from 28 days to six months, stabilising thereafter. At 12 months, IgG levels were lower in the fractional compared with standard arm for ChAdOx1-S primed participants (GMR 0.78 [95% CI 0.63 - 0.96], p=0.017). At six and 12 months, the median sVNT inhibition percentages were comparable by study arm and priming strata. Documented SARS-CoV-2 infections occurred in 25 participants (fractional dose arm n=12; standard dose arm n=13). From 28 days, 228 undocumented infections (> 1.2-fold IgG increase) occurred (fractional arms n=112; standard arm n=116). SAEs (n=41) were balanced between arms, with no severe vaccine-related AEs and SAEs were reported. Conclusions Fractional and standard dose BNT162b2 boosters demonstrated comparable immunogenicity and favourable safety. Fractional COVID-19 vaccine booster doses may improve vaccine acceptability due to lower reactogenicity.

The National Centre for Communicable Diseases (NCCD) is part of the Mongolian Ministry of Health and is a focal point for WHO International Health Regulations. CDN receives funding from Merck Sharp & Dohme as a co-investigator/biostatistician on a Merck Investigator Studies Program grant on pneumococcal serotype epidemiology in children with empyema, and from Pfizer as a co-investigator/biostatistician on a clinical research collaboration on PCV vaccination in Mongolia. PVL receives funding from the Gates Foundation and the National Health and Medical Research Council (NHMRC, Australia). CvM is the principal investigator on a Pfizer clinical research collaborative grant on PCV vaccination in Mongolia. CvM has received honoraria from Pfizer and Merck for participation in expert panels. KMu was on the Data Safety Monitoring Board of a Novavax Covid-19 vaccine trial, which is now complete, and was funded to attend the October 2022 and March 2023 Strategic Advisory Group of Experts on Immunization (SAGE) meetings as a SAGE member. Other authors declare no competing interests.

NCT05265065

https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(23)00271-7/fulltext#supplementary-material

This study was funded by the Coalition for Epidemic Preparedness Innovations (CEPI). This study was supported by the Victorian Government's Operational Infrastructure Support Programme.

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Ethics Committee of the Ministry of Health, Ulaanbaatar, Mongolia, and the Human Research Ethics Committee of the Royal Children's Hospital, Melbourne, Australia, gave ethical approval for this work.

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