Comparative antibody and cell-mediated immune responses, reactogenicity, and efficacy of homologous and heterologous boosting with CoronaVac and BNT162b2 (Cobovax): an open-label, randomised trial

• Published in: The Lancet. Microbe 2023-09, Vol.4 (9), p.e670-e682
• Main Authors: Leung, Nancy H L, Cheng, Samuel M S, Cohen, Carolyn A, Martín-Sánchez, Mario, Au, Niki Y M, Luk, Leo L H, Tsang, Leo C H, Kwan, Kelvin K H, Chaothai, Sara, Fung, Lison W C, Cheung, Alan W L, Chan, Karl C K, Li, John K C, Ng, Yvonne Y, Kaewpreedee, Prathanporn, Jia, Janice Z, Ip, Dennis K M, Poon, Leo L M, Leung, Gabriel M, Peiris, J S Malik, Valkenburg, Sophie A, Cowling, Benjamin J
• Format: Article
• Language: English
• Subjects: Adult; Antibodies; BNT162 Vaccine; COVID-19 - prevention & control; COVID-19 Vaccines - adverse effects; Humans; Immunity; SARS-CoV-2
• ISSN: 2666-5247; 2666-5247
• DOI: 10.1016/S2666-5247(23)00216-1

Few trials have compared homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. The aim of this study was to assess immune responses, safety, and efficacy against SARS-CoV-2 infection following homologous or heterologous third-dose COVID-19 vaccination with either one dose of CoronaVac (Sinovac Biotech; inactivated vaccine) or BNT162b2 (Fosun Pharma–BioNTech; mRNA vaccine). This is an ongoing, randomised, allocation-concealed, open-label, comparator-controlled trial in adults aged 18 years or older enrolled from the community in Hong Kong, who had received two doses of CoronaVac or BNT162b2 at least 6 months earlier. Participants were randomly assigned, using a computer-generated sequence, in a 1:1 ratio with allocation concealment to receive a (third) dose of CoronaVac or BNT162b2 (ancestral virus strain), stratified by types of previous COVID-19 vaccination (homologous two doses of CoronaVac or BNT162b2). Participants were unmasked to group allocation after vaccination. The primary endpoint was serum neutralising antibodies against the ancestral virus at day 28 after vaccination in each group, measured as plaque reduction neutralisation test (PRNT50) geometric mean titre (GMT). Surrogate virus neutralisation test (sVNT) mean inhibition percentage and PRNT50 titres against omicron BA.1 and BA.2 subvariants were also measured. Secondary endpoints included geometric mean fold rise (GMFR) in antibody titres; incidence of solicited local and systemic adverse events; IFNγ+ CD4+ and IFNγ+ CD8+ T-cell responses at days 7 and 28; and incidence of COVID-19. Within-group comparisons of boost in immunogenicity from baseline and between-group comparisons were done according to intervention received (ie, per protocol) by paired and unpaired t test, respectively, and cumulative incidence of infection was compared using Kaplan-Meier curves and a proportional hazards model to estimate hazard ratio. The trial is registered with ClinicalTrials.gov, NCT05057169. We enrolled participants from Nov 12, 2021, to Jan 27, 2022. We vaccinated 219 participants who previously received two doses of CoronaVac, including 101 randomly assigned to receive CoronaVac (CC-C) and 118 randomly assigned to receive BNT162b2 (CC-B) as their third dose; and 232 participants who previously received two doses of BNT162b2, including 118 randomly assigned to receive CoronaVac (BB-C) and 114 randomly assigned to receive BNT162b2 (BB-B) as their thi