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

Our take —

This was a prospective study of healthcare professionals from Germany who had already received a priming dose of ChAdOx1 nCoV-19 (AstraZeneca) vaccine. Participants were offered a choice between ChAd or BNT162b2 (Pfizer/BioNTech) for their second dose of vaccine. Both prime-boost strategies enhanced the humoral and cellular immune responses against SARS-CoV-2. However, the group boosted with BNT162b2 showed significantly stronger immune responses compared to the group boosted with ChAdOx-nCov-19.

Study design


Study population and setting

Prime-boost vaccination strategies with different COVID-19 vaccines (heterologous) versus the same vaccines (homologous) have not yet been formally studied. This is now becoming a real-world issue since many have received first dose of AstraZeneca’s ChAdOx1-nCov-19 (ChAd) vaccine, and it is now advised only for individuals older than 60 years due to thromboembolic events. The aim of this study was to analyze the immunogenicity induced by a heterologous prime-boost vaccination schedule, using the ChAd vaccine as the priming dose and Pfizer/BioNTech’s BNT162b2 (BNT) vaccine as the booster dose. The study used participants from Hannover Medical School’s COVID-19 Contact (CoCo) Study cohort of healthcare professionals, ranging from ages 19 through 64 years, who had already received a priming dose of ChAd. Participants were offered a choice between ChAd or BNT162b2 for their second dose of vaccine. 32 participants chose homologous boost of ChAd, and 55 participants chose heterologous boost using BNT. A control group of 46 participants who received a both a prime and booster dose of BNT was also included. ChAd-primed immune responses were then monitored prior to and 3 weeks following booster with either ChAd or BioNTech/Pfizer’s BNT162b2 vaccine.

Summary of Main Findings

Prior to booster dose, similar levels of IgG and IgA antibodies were detected in both ChAd/ChAd and ChAd/BNT groups, showing that both groups responded equally well after the ChAd priming dose. After booster dose, both vaccines boosted prime induced immunity. BNT induced significantly higher frequencies of spike specific T-cells compared to ChAd. Both vaccines caused increased amounts of spike-specific memory B cells after booster immunization. The BNT vaccine induced higher titers of neutralizing antibodies against all three variants of concern studied here: B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma). On the other hand, in the ChAd/ChAd group, the booster dose increased neutralization of the Alpha variant, but no effect was seen against Beta and Gamma variants. There were no significant differences between age groups or sexes.

Study Strengths

The study included a control group of participants who received homologous prime-boost strategy of BNT vaccine. It also investigated multiple components of immune system, as well as the immune response against several variants of concern.


There was no randomization of patients due to the set-up of the study, and therefore the authors were unable to completely exclude confounding factors. The data was collected in a cohort of generally healthy, young, healthcare professionals, and thus the findings may not generalize to older people or specific patient groups with comorbidities, both of whom are important to consider when studying vaccines for COVID-19. Participants were also about 75% female, which is not representative of the general population. Finally, the Delta variant was not studied here.

Value added

First study testing immunogenicity induced by heterologous prime-boost strategy with ChAdOx-nCov-19 and BNT162b2.

This review was posted on: 9 August 2021