Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19

During the first year of the COVID-19 pandemic, several clinical trials provided evidence of the efficacy of a number of candidate vaccines against SARS-CoV-21. However, with new COVID-19 waves and global vaccine shortages, the benefits of mixing two vaccines into one heterologous vaccination regimen are apparent and point toward a possibility of implementing this regimen to reach broad vaccine coverage2. A heterologous vaccination regimen may also be needed to maintain protective immunity against SARS-CoV-2 over time. Finally, the use of a different vaccine has been suggested as a way to overcome hesitancy in persons who received a first dose of an adenoviral-vectored vaccine for which safety concerns were raised. In fact, several European countries, such as Spain and Germany, have implemented a booster dose with mRNA vaccines to people under the age of 60 that received primary vaccination with ChAdOx1-nCOV19.

There is experimental evidence suggesting that heterologous vaccination improves the immune responses3 and indeed this strategy has been proposed in vaccination against other viruses4 and cancer5. Preclinical data in mice confirm the immunological benefit of combining COVID-19 vaccines from different platforms6,7 and several clinical trials are presently underway to test the safety and immunogenicity of this strategy for SARS-CoV2 infection (NCT04907331, NCT04962906, NCT04760730, NCT04684446, and NCT0477631).

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