The two-dose vaccine schedule widely involves the use of the inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac). Researchers herein examined if immune responses could be boosted by administering a third dose of the homologous or a different vaccine.

• In RHH-001, a phase 4, participant masked, two center, safety and immunogenicity study, Brazilian adults (18 years and older) in São Paulo or Salvador, who had received two doses of CoronaVac 6 months previously, were offered a third heterologous dose of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer–BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac.

• Researchers randomly assigned a total of 1,240 participants to one of the four groups, of whom 1,239 were vaccinated and 1,205 were eligible for inclusion in the primary analysis.

• At 6 months after previous immunization with two doses of CoronaVac, there were low antibody concentrations.

• However, a significant increase occurred in binding and neutralizing antibodies in correlation with all four vaccines administered as a third dose, which could result in improved protection against infection.

• More robust immune responses were induced and there might be enhanced protection in correlation with heterologous boosting vs homologous boosting.