Interchangeability of different COVID-19 vaccine platforms as booster doses: A phase 3 study mimicking real-world practice

Sue Ann Costa Clemens; Lily Weckx; Eveline P Milan; Igor Smolenov; Ralf Clemens

doi:10.1016/j.vaccine.2024.05.009

Interchangeability of different COVID-19 vaccine platforms as booster doses: A phase 3 study mimicking real-world practice

Vaccine. 2024 May 17:S0264-410X(24)00555-3. doi: 10.1016/j.vaccine.2024.05.009. Online ahead of print.

Authors

Sue Ann Costa Clemens¹, Lily Weckx², Eveline P Milan³, Igor Smolenov⁴, Ralf Clemens⁵

Affiliations

¹ Institute for Global Health, University of Siena, Siena, Italy; Department of Pediatrics, Oxford University, Oxford, UK. Electronic address: clemens.ralf@outlook.com.
² CRIE UNIFESP, Reference Center for Special Immunobiologicals, Federal University of São Paulo, São Paulo, Brazil.
³ Centro de Estudos e Pesquisa em Moléstias Infecciosas Ltda. (CEPCLIN), Natal, Brazil.
⁴ Clover Biopharmaceuticals, Chengdu, China.
⁵ International Vaccine Institute IVI BOT, Seoul, Republic of Korea.

PMID: 38762360
DOI: 10.1016/j.vaccine.2024.05.009

Abstract

Background: The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2 variants. We assessed safety and immunogenicity of booster doses of COVID-19 vaccines based on three different platforms in a setting that mimics the current routine practice in Brazil.

Methods: In this phase 3 study from 14 February 2023 to 12 June 2023 we enrolled previously immunized adults to receive an additional booster dose of one of three vaccines. Immunogenicity against ancestor SARS-CoV-2 and Omicron BF.7, BQ.1.1.3, and XBB.1.5.6 sub-lineages was measured as ELISA IgG or virus neutralizing (VNT) antibodies and safety/reactogenicity assessed using diary cards.

Results: Volunteers with a history of full primary COVID-19 immunization striated to three cohorts according to their previous booster vaccination history-0 (n = 26), 1 (n = 140) or 2 (n = 606) booster vaccinations-were randomized 2:1:1 to receive either recombinant protein (SCB-2019, Clover), adenovirus-vector (ChAdOx1-S, AstraZeneca/Fiocruz), or mRNA (BNT162b2, Pfizer/Wyeth). Baseline antibody titers were higher in individuals who had received one or two boosters and titers against both ancestor and Omicron sub-lineages increased in all groups regardless of the number of previous booster doses or the vaccine used. Day 28 geometric mean titers (GMTs) and geometric mean-fold rises (GMFR) against all variants were higher after BNT162b than SCB-2019 or ChAdOx1-S, but BNT162b groups displayed more rapid antibody waning at Day 84. Within cohorts each vaccine elicited similar GMFR against the different SARS-CoV-2 strains. All vaccines were well tolerated with similar solicited reactogenicity profiles.

Conclusions: Protein, adenovirus-vector or mRNA vaccine boosters were equally well tolerated and immunogenic against ancestor SARS-CoV-2 and Omicron sub-lineages in fully primed adults with 0-2 prior boosters. BNT162b induced the highest immune responses but also the most rapid waning of antibodies 3 months after vaccination.

Clinical trial registration: ClinicalTrials.gov, identifier NCT05812586.

Keywords: Protein vaccine; SARS-CoV-2; Vector vaccine; mRNA vaccine.

Associated data

ClinicalTrials.gov/NCT05812586