Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron

recipients of either the BNT162b2 or mRNA-1273 vaccine), we observed 362 documented infections, including 23 participants with moderate disease and 8 with severe or critical disease.No material difference was noted in the incidence of SARS-CoV-2 infection, including moderate and severe or critical disease, among participants who had received heterologous or homologous boosting after primary mRNA vaccination (adjusted rate ratio, 1.10; 95% CI, 0.90 to 1.35).Outcomes for the individual mRNA vaccines were similar to those in the combined mRNA category.(Additional data regarding individual vaccines are provided in Table S2.)Recent clinical trials examining the safety and immunogenicity of SARS-CoV-2 boosters in healthy adults have shown greater increases in antibody titers after heterologous boosting than after homologous boosting.2,5 In particular, neutralizing immunoglobulin G antibodies were lowest after homologous Ad26.COV2.S boosting and remained below the predicted efficacy threshold for preventing symptomatic Covid-19.2 Our findings support the results of these clinical trials since we observed the largest number of documented breakthrough infections in participants who had received a homologous Ad26.COV2.S booster.Our analysis provides further evidence that the infection rate is lower in persons who are boosted with a heterologous mRNA vaccine.Overall, documented infections, including moderate and severe or critical disease, were uncommon among veterans who had received either homologous or heterologous boosters.Heterologous mRNA boosting may better protect against incident infection in persons who were initially vaccinated with an adenoviralvector vaccine.