Differential heterologous immunological effects induced by ChAdOx1-S and BNT162b2 COVID-19 vaccines

The mRNA- and adenovirus-based COVID-19 vaccines may induce different heterologous effects on non-COVID morbidity. We aimed to investigate immunological mechanisms that may account for these differences.

We selected a subgroup of individuals from the TACTIC trial who had completed their COVID-19 vaccination scheme before the introduction of a BNT162b2 booster vaccine. Transcriptional activity, distribution of cell types and cytokine secretion were compared between those who were originally vaccinated with the adenovirus vaccine ChAdOx1-S, and those who had received the mRNA vaccine BNT162b2. Additionally, we investigated how these differences evolved after administration of a BNT162b2 booster vaccine.

24 individuals were included in this study, with 15 volunteers (62.5%) having originally received an mRNA vaccine and 9 (37.5%) an adenovirus vector vaccine. We found that 84 gene sets were differentially expressed in PBMCs from the two vaccine groups following ex-vivo secondary stimulation. Although cell populations did not significantly differ, pro-inflammatory cytokine responses to most stimuli were consistently higher in the adenovirus group compared to the mRNA group. These differences decreased after an mRNA booster vaccine.

Our study findings provide additional support to the hypothesis that mRNA- and adenovirus-based vaccines differ in their broad immunological effects. Specifically, our observation that adenovirus-based vaccination tends to result in higher pro-inflammatory cytokine responses might help explain the difference in the heterologous effects of the two types of vaccines. Knowledge about NSEs is increasingly important for making public health and policy decisions, particularly for vulnerable populations.