Author reply to “Heterologous mRNA-based COVID-19 booster strategies: Comment”

Abstract

Dear Editor, We welcome the opportunity to reply to “Heterologous mRNA-based COVID-19 booster strategies: comment” 1 regarding our published article titled “Emerging heterologous mRNA-based booster strategies within the COVID-19 vaccine landscape.” 2 We appreciate the salient points raised within this commentary. Importantly, many regulatory bodies have authorized and/or approved the use of heterologous boosting regimens, with several vaccine recommending bodies and the World Health Organization (WHO) supporting their use. Recent data from a large, phase 3, randomized trial in the United Kingdom support these recommendations, wherein the efficacy, immunogenicity, and safety of a booster dose of the original mRNA-based COVID-19 vaccine (mRNA-1273) or variant-containing omicron (BA.1) booster vaccines (mRNA-1273.529 or mRNA-1273.214) administered after any COVID-19 primary vaccination schedule (primarily BNT162b2 or ChAdOx1-SARS-CoV-2 vaccines) were compared. 3 Overall, all mRNA-based vaccine booster regimens induced robust immune responses against omicron BA.1, with COVID-19 incidence numerically lower for the BA.1-containing vaccines than the original vaccine. These data highlight the utility of a heterologous booster regimen for continued protection against COVID-19. Additional real-world and clinical trial studies should further inform on the potential differences of variable heterologous boosting regimens. We acknowledge that heterologous booster regimens are currently not the standard schedule for many countries worldwide, with vaccination regimens largely dictated by logistical factors such as local vaccine manufacturing and vaccine availability. However, it remains notable that among those regions and countries where a heterologous vaccination schedule has been implemented, these regimens have shown improved immunogenicity that complement the various primary regimens. Accordingly, when applicable, additional considerations for heterologous boosters after region-specific primary vaccination regimens may help to optimize protection against COVID-19.