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

BackgroundThere are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. MethodsWe 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. ResultsWe 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. Antibody responses against the ancestral virus, Omicron BA.1 and BA.2 subvariant by surrogate neutralization and PRNT50 were stronger for the recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. CD4+ T cells boost only occurred in CoronaVac-primed arms. We did not identify differences in CD4+ and CD8+ T cell responses between arms. 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). ConclusionsSimilar 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.

Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine

IntroductionThird doses of COVID-19 vaccination provide an important boost to immunity, reducing the risk of symptomatic infection and the risk of severe disease. Third doses have been particularly important for improving protection against variants. However, waning of clinical protection particularly against Omicron has been noted after receipt of third doses. MethodsWe administered BNT162b2 as a third dose to adults aged [≥]30 years who had previously received two doses of inactivated vaccination. We collected blood before the third dose and again after one month and six months, and tested sera using a spike receptor binding domain IgG enzyme-linked immunosorbent assay, a surrogate virus neutralization test, and live virus plaque reduction neutralization assay against ancestral virus and Omicron BA.2. ResultsWe administered BNT162b2 as a third dose to 314 adults. We found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 were weaker after the third dose and had declined to a low level by six months. From a small number of participants we observed that natural infection or a fourth dose of vaccination generated similar antibody levels against ancestral virus, but infection generated higher antibody level against Omicron BA.2 than vaccination, suggesting a potential advantage in the breadth of antibody response from hybrid immunity. ConclusionsWhile antibody levels against the ancestral strain remained robust at six months after the third dose, antibody levels against Omicron BA.2 had fallen to low levels suggesting the potential benefits of a fourth dose.

Strength and durability of antibody responses to BNT162b2 and CoronaVac

We studied 2780 adults in Hong Kong who received CoronaVac inactivated virus vaccine (Sinovac) and BNT162b2 mRNA vaccine ("Comirnaty", BioNTech/Fosun Pharma). We found stronger and more durable antibody responses to two doses of the mRNA vaccine, and slightly stronger initial antibody responses to each vaccine in younger adults and women.

BNT162b2 vaccine boosts neutralizing antibodies to ancestral SARS-CoV-2 & Omicron variant in adults who previously received two doses of inactivated vaccine

BackgroundLimited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants. MethodsWe conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged [≥]30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. ResultsIn 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p<0. 001), and mean sVNT levels increased from an inhibition of 17% to 96% (p<0.001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by at least 24 fold from Day 0 to Day 28 against the ancestral virus (p<0.001) and rose by at least 11 fold against the Omicron variant (p<0.001). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants. ConclusionsA third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier. SummaryIn this open label trial of Chinese adults aged [≥]30 years who received two doses of inactivated COVID-19 vaccine 6 months earlier, third-dose mRNA vaccine substantially improved antibody levels against the ancestral virus and Omicron variant with well-tolerated safety profile.

A RCT of a third dose CoronaVac or BNT162b2 vaccine in adults with two doses of CoronaVac

BackgroundPoor immunogenicity and antibody waning were found in vaccinees of CoronaVac. There is lack of randomized controlled trial (RCT) data to compare the immunogenicity and safety of schedules using homologous and heterologous vaccine as a booster dose. MethodsWe randomly assigned adults who had received 2 doses of CoronaVac with low antibody response to receive an additional booster dose of either BNT162b2 or CoronaVac. The local and systemic adverse reactions were recorded. Levels of SARS-CoV-2 neutralizing and spike binding antibody in plasma were measured. FindingsAt one month after the third dose of vaccine, BNT162b2 vaccines elicited significantly higher surrogate virus neutralizing test (sVNT), spike receptor binding, spike N terminal domain binding, spike S2 domain binding levels than CoronaVac. More participants from the BNT162b2 group reported injection site pain and swelling as well as fatigue and muscle pain than those who received CoronaVac as the third dose. The mean results of the sVNT against the wild type, beta, gamma and delta variants in the BNT162b2 boosted group was 96.83%, 92.29%, 92.51% and 95.33% respectively which were significantly higher than the CoronaVac boosted group (Wild type: 57.75%; Beta: 38.79 %; Gamma: 32.22%; Delta: 48.87%) ConclusionOur RCT study shows that BNT162b2 booster dose for those people who poorly responded to the previous vaccination of CoronaVac is significantly more immunogenic than a CoronaVac booster. BNT162b2 also elicits higher levels of SARS-CoV-2 specific neutralizing antibodies to different variants of concern. The adverse reactions were only mild and short-lived. At a Glance CommentaryO_ST_ABSScientific Knowledge on the SubjectC_ST_ABSPoor immunogenicity and antibody waning were found in vaccinees of CoronaVac. There is lack of randomized controlled trial (RCT) data to compare the immunogenicity and safety of schedules using homologous and heterologous vaccine as a booster dose. What This Study Adds to the FieldOur RCT study shows that BNT162b2 booster dose for those people who poorly responded to the previous vaccination of CoronaVac is significantly more immunogenic than a CoronaVac booster. The adverse reactions were only mild and short-lived.