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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

See all articles by Tsetsegsaikhan Batmunkh

Tsetsegsaikhan Batmunkh

National Center for Communicable Diseases

Kerryn Moore

University of Melbourne - Infection and Immunity

Helen Thomson

University of Melbourne - Infection and Immunity

Bolor Altangerel

Onoshmed Laboratory

Otgonjargal Amraa

National Center for Communicable Diseases

Naranbaatar Avaa

Onoshmed Laboratory

Lkhagvagaram Batbayar

Sukhbaatar District Health Centre

Khishigjargal Batsukh

First Central Hospital of Mongolia - General Laboratory of Clinical Pathology

Kathryn Bright

University of Melbourne - Infection and Immunity

Tsogjargal Burentogtokh

First Central Hospital of Mongolia - General Laboratory of Clinical Pathology

Lien Anh Ha Do

University of Melbourne - Infection and Immunity

Gantuya Dorj

Mongolian National University of Medical Sciences

John D. Hart

University of Melbourne - Infection and Immunity

Khulan Javkhlantugs

Bayangol District Health Centre

Sarantsetseg Jigjidsuren

First Central Hospital of Mongolia - General Laboratory of Clinical Pathology

Frances Justice

University of Melbourne - Infection and Immunity

Shuo Li

University of Melbourne - Infection and Immunity

Paul V. Licciardi

University of Melbourne - Infection and Immunity

Khaliunaa Mashbaatar

National Center for Communicable Diseases

Nadia Mazarakis

University of Melbourne - Infection and Immunity

Eleanor FG Neal

University of Melbourne - Infection and Immunity

Cattram D. Nguyen

University of Melbourne - Infection and Immunity

Batbayar Ochirbat

Ministry of Health, Mongolia

Bilegtsaikhan Tsolmon

National Center for Communicable Diseases

Alimaa Tuya

Onoshmed Laboratory

Unursaikhan Surenjav

National Centre for Public Health (Mongolia)

Claire von Mollendorf

University of Melbourne - Infection and Immunity

Kim Mulholland

University of Melbourne - Infection and Immunity

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

Suggested Citation

Batmunkh, Tsetsegsaikhan and Moore, Kerryn and Thomson, Helen and Altangerel, Bolor and Amraa, Otgonjargal and Avaa, Naranbaatar and Batbayar, Lkhagvagaram and Batsukh, Khishigjargal and Bright, Kathryn and Burentogtokh, Tsogjargal and Do, Lien Anh Ha and Dorj, Gantuya and Hart, John D. and Javkhlantugs, Khulan and Jigjidsuren, Sarantsetseg and Justice, Frances and Li, Shuo and Licciardi, Paul V. and Mashbaatar, Khaliunaa and Mazarakis, Nadia and Neal, Eleanor FG and Nguyen, Cattram D. and Ochirbat, Batbayar and Tsolmon, Bilegtsaikhan and Tuya, Alimaa and Surenjav, Unursaikhan and von Mollendorf, Claire and Mulholland, Kim, 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. Available at SSRN: https://ssrn.com/abstract=4404854 or http://dx.doi.org/10.2139/ssrn.4404854

Tsetsegsaikhan Batmunkh

National Center for Communicable Diseases ( email )

Kerryn Moore

University of Melbourne - Infection and Immunity ( email )

Helen Thomson

University of Melbourne - Infection and Immunity ( email )

Bolor Altangerel

Onoshmed Laboratory ( email )

Otgonjargal Amraa

National Center for Communicable Diseases ( email )

Naranbaatar Avaa

Onoshmed Laboratory ( email )

Lkhagvagaram Batbayar

Sukhbaatar District Health Centre ( email )

Khishigjargal Batsukh

First Central Hospital of Mongolia - General Laboratory of Clinical Pathology ( email )

Kathryn Bright

University of Melbourne - Infection and Immunity ( email )

Tsogjargal Burentogtokh

First Central Hospital of Mongolia - General Laboratory of Clinical Pathology ( email )

Lien Anh Ha Do

University of Melbourne - Infection and Immunity

Gantuya Dorj

Mongolian National University of Medical Sciences ( email )

Mongolia

John D. Hart

University of Melbourne - Infection and Immunity ( email )

Khulan Javkhlantugs

Bayangol District Health Centre ( email )

Sarantsetseg Jigjidsuren

First Central Hospital of Mongolia - General Laboratory of Clinical Pathology ( email )

Frances Justice

University of Melbourne - Infection and Immunity ( email )

Shuo Li

University of Melbourne - Infection and Immunity ( email )

Paul V. Licciardi

University of Melbourne - Infection and Immunity ( email )

Australia

Khaliunaa Mashbaatar

National Center for Communicable Diseases ( email )

Nadia Mazarakis

University of Melbourne - Infection and Immunity ( email )

Eleanor FG Neal

University of Melbourne - Infection and Immunity ( email )

Cattram D. Nguyen

University of Melbourne - Infection and Immunity ( email )

Batbayar Ochirbat

Ministry of Health, Mongolia ( email )

Bilegtsaikhan Tsolmon

National Center for Communicable Diseases ( email )

Alimaa Tuya

Onoshmed Laboratory ( email )

Unursaikhan Surenjav

National Centre for Public Health (Mongolia) ( email )

Claire Von Mollendorf

University of Melbourne - Infection and Immunity ( email )

Kim Mulholland (Contact Author)

University of Melbourne - Infection and Immunity ( email )

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