Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)

Abstract

Background: There are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. Methods: We conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. Results: We enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac ("CC-C", n=101) or BNT162b2 ("CC-B", n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac ("BB-C", n=118) or BNT162b2 ("BB-B", n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Third doses significantly increased neutralising PRNT50 antibody titers against ancestral virus and Omicron BA.1 variant in all four study arms, and against Omicron BA.2 in all arms except CC-C, with statistically significant improvements for recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. Boosting of CD4+ T cells only occurred in CoronaVac-primed arms, but we did not identify overall differences between vaccine groups in CD4+ and CD8+ T cell responses. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). Conclusions: Similar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.

Durability for 12 months of antibody response to a booster dose of monovalent BNT162b2 in adults who had initially received 2 doses of inactivated vaccine

“…Our study has several other limitations. We observed an infection rate of 24% in our cohort, which was slightly less than the estimated 41% infection rate during the Omicron wave in Hong Kong [12], although receipt of the third dose in our study between October and December 2021 might have provided some degree of protection against confirmed SARS-CoV-2 infection in March 2022 [10,13]. Only one participant reported two episodes of COVID-19 infection during .…”

Safety and immunogenicity of a bivalent SARS-CoV-2 protein booster vaccine, SCTV01C, in adults previously vaccinated with mRNA vaccine: a randomized, double-blind, placebo-controlled phase 1/2 clinical trial

“…Table 5 compared the GMTs results of this study with those from the previous studies with the Pfizer BNT162b2 booster. 26 , 27 , 28 …”

Neutralizing and Total/IgG Spike Antibody Responses Following Homologous CoronaVac vs. BNT162b2 Vaccination Up to 90 Days Post-Booster

“…This was conducted with slightly different dosing intervals of 61–160 days (CoronaVac) and 180–234 days (BNT162b2) between the second and third doses. In another study where COVID-19-naïve subjects (101 CoronaVac and 114 BNT162b2) received a homologous booster >6 months after their second vaccination (median days between first and second doses/second and third doses: CoronaVac, 27/232; BNT162b2, 21/222) [ 27 ], the geometric mean titers of N-Abs also showed responses similar to those in the vaccinees in our study, with 1- vs. 13-fold increases in N-Abs against the Omicron variant in CoronaVac vs. BNT162b2 vaccinees. Thus, even with different dosing intervals, the differences between CoronaVac and BNT162b2 antibody responses seem to follow a similar trend.…”