Originally published by 2 Minute Medicine^® (view original article). Reused on AccessMedicine with permission.

1. Heterologous AstraZeneca followed by Pfizer vaccination was noninferior to homologous, two-dose AstraZeneca vaccination with a geometric mean ratio of 9.2.

2. Heterologous Pfizer followed by AstraZeneca vaccination was not found to be non-inferior to homologous, two-dose Pfizer vaccination.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Heterologous prime-boost vaccination schedules involve administering two different types of vaccines. While heterologous vaccination schedules would reduce many logistical barriers in vaccine distribution, their relative efficacies have not yet been reported. Two major vaccines for COVID-19 were included in this study: the BioNTech-Pfizer mRNA vaccine (BNT) and the AstraZeneca ChAdOx1 adenovirus vaccine (ChAd). COVID vaccine-naive participants were blinded and randomized to different vaccination schedules: BNT/BNT, ChAd/ChAd, ChAd/BNT, BNT/ChAd with 28 days between doses. The vaccine effectiveness was measured by SARS-CoV-2 anti-spike IgG concentration ratios. Results showed that heterologous ChAd/BNT vaccination order was non-inferior to ChAd/ChAd. However, the study also reported that a heterologous BNT/ChAd schedule could not be considered non-inferior to the homologous BNT/BNT schedule. Overall, it was shown that all the evaluated vaccine combination schedules produced higher IgG concentration than the homologous ChAd/ChAd, an approved schedule with proven efficacy. Therefore, heterologous vaccination schedules could be considered in the case of vaccination shortage.

Click to read the study in the Lancet

Relevant Reading: Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination

In-Depth [randomized controlled trial]:

Com-COV is a UK-based non-inferiority study investigating heterologous prime-boost COVID-19 vaccine schedules. 830 participants were randomized 1:1:1:1 to each vaccination schedule at intervals of 28 days and 84 days, but only the 28 day interval was reported in this study. Mean age of the participants was 57.8 years with 46% being female. The primary outcome was measured SARS-CoV-2 anti-spike IgG concentration 28 days after the booster dose. Results found non-inferiority of ChAd/BNT to ChAd/ChAd at a geometric mean ratio (GMR) of 9.2 (prespecified non-inferiority threshold = 0.63), but did not report non-inferiority of BNT/ChAd to BNT/BNT at a ratio of 0.51. Absolute concentrations were highest in BNT/BNT (14 080 ELU/ml), followed by ChAd/BNT (12 906 ELU/ml), BNT/ChAd (7133 ELU/ml), and ChAd/ChAd (1392 ELU/ml). No serious adverse events were attributed to the vaccinations.

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