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

Tsetsegsaikhan Batmunkh; Kerryn A Moore; Helen Thomson; Bolor Altangerel; Otgonjargal Amraa; Naranbaatar Avaa; Lkhagvagaram Batbayar; Khishigjargal Batsukh; Kathryn Bright; Tsogjargal Burentogtokh; Lien Anh Ha Do; Gantuya Dorj; John D Hart; Khulan Javkhlantugs; Sarantsetseg Jigjidsuren; Frances Justice; Shuo Li; Paul V Licciardi; Khaliunaa Mashbaatar; Nadia Mazarakis; Eleanor F G Neal; Cattram Duong Nguyen; Batbayar Ochirbat; Bilegtsaikhan Tsolmon; Alimaa Tuya; Unursaikhan Surenjav; Claire von Mollendorf; Kim Mulholland

doi:10.1016/j.lanwpc.2023.100953

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

Lancet Reg Health West Pac. 2023 Nov 21:42:100953. doi: 10.1016/j.lanwpc.2023.100953. eCollection 2024 Jan.

Authors

Tsetsegsaikhan Batmunkh¹, Kerryn A Moore², Helen Thomson², Bolor Altangerel³, Otgonjargal Amraa¹, Naranbaatar Avaa³, Lkhagvagaram Batbayar⁴, Khishigjargal Batsukh⁵, Kathryn Bright², Tsogjargal Burentogtokh⁵, Lien Anh Ha Do^{2

6}, Gantuya Dorj⁷, John D Hart², Khulan Javkhlantugs⁸, Sarantsetseg Jigjidsuren⁵, Frances Justice², Shuo Li², Paul V Licciardi^{2

6}, Khaliunaa Mashbaatar¹, Nadia Mazarakis², Eleanor F G Neal^{2

6}, Cattram Duong Nguyen², Batbayar Ochirbat⁹, Bilegtsaikhan Tsolmon^{1

7}, Alimaa Tuya³, Unursaikhan Surenjav¹⁰, Claire von Mollendorf^{2

6}, Kim Mulholland²

Affiliations

¹ National Centre for Communicable Diseases, Ulaanbaatar, Mongolia.
² Infection and Immunity, Murdoch Children's Research Institute, Royal Children's Hospital, Australia.
³ Onoshmed Laboratory, Sukhbaatar District, Ulaanbaatar, Mongolia.
⁴ Sukhbaatar District Health Centre, Sukhbaatar District, Ulaanbaatar, Mongolia.
⁵ General Laboratory of Clinical Pathology, First Central Hospital of Mongolia, Ulaanbaatar, Mongolia.
⁶ Department of Paediatrics, The University of Melbourne, Parkville, Australia.
⁷ Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia.
⁸ Bayangol District Health Centre, Bayangol District, Ulaanbaatar, Mongolia.
⁹ Mongolia Ministry of Health, Sukhbaatar District, Ulaanbaatar, Mongolia.
¹⁰ National Centre for Public Health, Ulaanbaatar, Mongolia.

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, n = 129 participants), BBIBP-CorV (Sinopharm (Beijing), n = 399), or Gam-COVID-Vac (Gamaleya, n = 70) schedule. Participants were randomised (1:1) to receive a 15 μg (half-dose) or 30 μg (full-dose) BNT162b2 booster. Participants and study staff assessing reactogenicity were blinded up to day 28. Co-primary endpoints were Wuhan-Hu-1 anti-spike S1 IgG seroresponse 28 days post-boosting and reactogenicity within 7 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 randomized to full-dose BNT162b2 (n = 300) or half-dose (n = 301). 598 were included in safety analyses, and 587 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 titres were similar in those receiving full and half-dose boosters for the ChAdOx1 and BBIBP-CorV primed groups, but 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.

Funding: Coalition for Epidemic Preparedness Innovations (CEPI).

Keywords: BBIP-CorV; BNT162b2; Booster; COVID-19; ChAdOx1; Fractional dose; Gam-COVID-Vac; Half-dose; SARS-CoV-2; Sputnik V; Vaccination.

Associated data

ClinicalTrials.gov/NCT05265065