COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Primary Prevention Banki Z, Mateus J, Rossler A, et al. Heterologous ChAdOx1/BNT162b2 vaccination induces stronger immune response than homologous ChAdOx1 vaccination: The pragmatic, multi-center, three-arm, partially randomized HEVACC trial. EBioMedicine. 2022 Jun;80:104073. doi: 10.1016/j.ebiom.2022.104073. Epub 2022 May 23.
PICO Terms
adult (P) adverse reactions; safety (O) ChAdOx-1-S primed with BNT162b2 booster (I/C) Comirnaty; Pfizer vaccine; BNT162b2; BioNTech/Fosun Pharma; mRNA (I/C) fully vaccinated (I/C) healthy (P) heterologous, prime-boost (I/C) immunogenicity (O) neutralizing antibodies (O) reactogenicity (O) SARS-CoV-2 spike protein-binding antibodies (O) spike-specific T cell response (O) T-cell response (O) vaccine efficacy (O) Vaxzevria; AstraZeneca vaccine; ChAd0x1 nCOV-19; non-replicating viral vector; adenovirus; University of Oxford/AstraZeneca; AZD1222 (I/C)
Demographic Information
Female Male
Not reported

BACKGROUND: Several COVID-19 vaccines have been approved. The mRNA vaccine from Pfizer/BioNTech (Comirnaty, BNT162b2; BNT) and the vector vaccine from AstraZeneca (Vaxzevria, ChAdOx1; AZ) have been widely used. mRNA vaccines induce high antibody and T cell responses, also to SARS-CoV-2 variants, but are costlier and less stable than the slightly less effective vector vaccines. For vector vaccines, heterologous vaccination schedules have generally proven more effective than homologous schedules.

METHODS: In the HEVACC three-arm, single-blinded, adaptive design study ( Identifier: NCT04907331), participants between 18 and 65 years with no prior history of SARS-CoV-2 infection and a first dose of AZ or BNT were included. The AZ/AZ and the AZ/BNT arms were randomized (in a 1:1 ratio stratified by sex and trial site) and single-blinded, the third arm (BNT/BNT) was observational. We compared the reactogenicity between the study arms and hypothesized that immunogenicity was higher for the heterologous AZ/BNT compared to the homologous AZ/AZ regimen using neutralizing antibody titers as primary endpoint.

FINDINGS: This interim analysis was conducted after 234 participants had been randomized and 254 immunized (N=109 AZ/AZ, N=115 AZ/BNZ, N=30 BNT/BNT). Heterologous AZ/BNT vaccination was well tolerated without study-related severe adverse events. Neutralizing antibody titers on day 30 were statistically significant higher in the AZ/BNT and the BNT/BNT groups than in the AZ/AZ group, for B.1.617.2 (Delta) AZ/AZ median reciprocal titer 75.9 (99.9% CI 58.0 - 132.5), AZ/BNT 571.5 (99.9% CI 396.6 - 733.1), and BNT/BNT 404.5 (99.9% CI 68.3 - 1024). Similarly, the frequency and multifunctionality of spike-specific T cell responses was comparable between the AZ/BNT and the BNT/BNT groups, but lower in the AZ/AZ vaccinees.

INTERPRETATION: This study clearly shows the immunogenicity and safety of heterologous AZ/BNT vaccination and encourages further studies on heterologous vaccination schedules.

FUNDING: This work was supported by the Medical University of Innsbruck, and partially funded by NIAID contracts No. 75N9301900065, 75N93021C00016, and 75N93019C00051.

Discipline / Specialty Area Score
Public Health