Heterologous ChAd/BNT schedule is well-tolerated, exhibits better immunogenicity than homologous ChAd/ChAd vaccination, and has comparable immunogenicity when compared to homologous BNT/BNT vaccination.

A systematic review was conducted to assess the safety, reactogenicity, and immunogenicity of heterologous (ChAd and BNT) versus homologous (ChAd or BNT) prime-boost immunization schedules.

Electronic databases such as Embase, Web of Science, and PubMed were searched for relevant literature. Overall, 13 studies and 3024 participants were incorporated for evaluation out of 14,571 records. A comparison was done of immunogenicity involving serum antibodies against various SARS-CoV-2 fragments, spike-specific T cells response, or neutralizing antibody. For conducting meta-analysis, pooling of local and systemic reactions was done.

Non-inferior anti-spike protein, better T cells response, and greater neutralizing antibody were induced by heterologous ChAd/BNT schedule in contrast to homologous BNT/BNT vaccination. In contrast to the homologous ChAd/ChAd immunization, heterologous ChAd/BNT (mRNA-1273) immunization elicited better anti-spike protein, greater neutralizing antibody and improved T cells response.

Contrasted to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT (mRNA-1273) had comparable risk of any reaction (risk ratio [RR] = 1.30) and greater risk of systemic reactions (RR = 1.49) and local reactions (RR = 1.65).

In heterologous ChAd/BNT (mRNA-1273) vaccination, a greater risk of local reactions (RR = 1.16),   and comparable risk of systemic reactions (RR = 0.89) and any reaction (RR = 1.03) was witnessed when compared to homologous BNT/BNT.

Hence, heterologous ChAd/BNT is a promising vaccination schedule to combat the COVID-19 pandemic.