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Immunogenicity, Safety, and Reactogenicity of a Half- Versus Full-Dose BNT162b2 (Pfizer-Biontech) Booster Following a Two-Dose ChAdOx1 nCoV-19, BBIBP-CorV, or Gam-COVID-Vac Priming Schedule in Mongolia: A Randomised, Controlled, Non-Inferiority Trial
25 Pages Posted: 3 Apr 2023
More...Abstract
Background: COVID-19 vaccine booster doses restore vaccine effectiveness lost from waning immunity and emerging variants. Fractional dosing may improve COVID-19 booster acceptability and uptake and will reduce the per-dose cost of COVID-19 booster programmes. We sought to quantify the immunogenicity, reactogenicity, and safety of a half-dose BNT162b2 (Pfizer-BioNtech) booster relative to the standard formulation.
Methods: This randomised, controlled, non-inferiority trial recruited adults in Mongolia primed with a two-dose homologous ChAdOx1 nCov-19 (Oxford-AstraZeneca), BBIBP-CorV (Sinopharm (Beijing)), or Gam-COVID-Vac (Gamaleya) schedule. Participants were randomised (1:1) to receive a 15μg (half-dose) or 30μg (full-dose) BNT162b2 booster. Co-primary endpoints were Wuhan-Hu-1 anti-spike S1 IgG seroresponse 28 days post-boosting and reactogenicity within seven days of boosting. The non-inferiority margin for the absolute difference in seroresponse was -10%. Differences in seroresponse were estimated from logistic regression with marginal standardisation. Geometric mean ratios of IgG were also estimated. ClinicalTrials·gov Identifier: NCT05265065.
Findings: Between May 27th and September 30th, 2022, 601 participants were randomised; 598 were included in safety analyses, and 587 were included in immunological analyses. The frequency of grade 3-4 reactions was similar between arms (half-dose: 4/299 [1·3%]; full-dose: 6/299 [2·0%]). Across all severity grades, half-dose recipients reported fewer local and systemic reactions (60% versus 72% and 25% versus 32%, respectively). Seroresponse was 84·7% (250/295) and 86·6% (253/292) in the half-dose and full-dose arms, respectively (Difference: -2·8%; 95% CI -7·7, 2·1). Geometric mean IgG titre was lower in the half-dose arm in Gam-COVID-Vac-primed participants (GMR: 0·71; 95% CI 0·54, 0·93).
Interpretation: Half-dose BNT162b2 boosting elicited an immune response that was non-inferior to a full-dose, with fewer reactions, in adults primed with ChAdOx1 nCov-19 or BBIBP-CorV. Half-dose boosting may not be suitable in adults primed with Gam-COVID-Vac. Half-dose BNT162b2 boosting may be considered in populations primed with ChAdOx1 nCov-19 or BBIBP-CorV.
Trial Registration: ClinicalTrials·gov Identifier: NCT05265065.
Funding: Coalition for Epidemic Preparedness Innovations (CEPI).
Declaration of Interest: 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). 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.
Ethical Approval: The trial was reviewed and approved by the Human Research Ethics Committee at the Royal Children’s Hospital Melbourne (HREC/81800/RCHM-2021) and the Mongolian Ethics Committee of the Ministry of Health (Decision #273, April 5th, 2022).
Keywords: COVID-19, SARS-CoV-2, vaccination, fractional dose, half-dose, booster, BNT162b2
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