The Effects of Heterologous Immunization with Prime-Boost COVID-19 Vaccination against SARS-CoV-2

Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the global challenge. Reaching global herd immunity will help end the COVID-19 pandemic. However, vaccine shortage and vaccine hesitancy are the obstacles to achieve global herd immunity against SARS-CoV-2. The current homologous vaccine regimen is experimentally switching to heterologous vaccination at several study sites. However, the reactogenicity of heterologous ChAdOx1-S and mRNA vaccination against SARS-CoV-2 is still unclear. We have conducted a systematic review to summarize the current findings on the safety and immunogenicity of this heterologous vaccination and elucidate their implications against SARS-CoV-2. This systematic review was conducted by the guidelines of PRISMA. Articles were searched from PubMed and other sources (MedRixv and Google scholar) starting from 1 January to 5 September 2021. The search term was heterologous ChAdOx1-S and BNT162b2 or mRNA-1273 vaccination. Our review found that participants with ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S did not have the serious adverse events seen with homologous vaccination. Participants with the heterologous regimen (ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S), compared with those with two doses of ChAdOx1-S, have shown a more robust immune responses against SARS-CoV-2, such as higher levels of responsive antibodies or increased numbers of spike-specific T-cells. Nevertheless, these immune responses were slightly diminished in the recipients of BNT162b2/ChAdOx1-S. Also, the safety study of heterologous ChAdOx1-S/mRNA vaccination was based on small populations. Further studies to enclose diverse categories, such as race/ethnicity or geography, may be necessary. Overall, the heterologous immunization with ChAdOX1-S and the mRNA vaccine may improve the vaccine shortage related slow pace of reaching herd immunity, especially using the heterologous immunization with ChAdOx1-S/BNT162b2.