Th1 polarization in Bordetella pertussis vaccine responses is maintained through a positive feedback loop.

Outbreaks of Bordetella pertussis (BP), the causative agent of whooping cough, continue despite broad vaccination coverage and have been increasing since vaccination switched from whole-BP (wP) to acellular BP (aP) vaccines. wP vaccination has been associated with more durable protective immunity and an induced Th1 polarized memory T cell response. Here, we profile, by a multi-omics approach, the immune response of 30 wP and 31 aP-primed individuals and identify correlates of T cell polarization before and after Tdap booster vaccination. We find that early transcriptional changes indicating an interferon response, followed by an increase in plasma IFN-γ and interferon-induced chemokine levels (peaking at day 1-3 post-booster), correlate best with the Th1 polarization of the vaccine-induced memory T cell response on day 28. Our studies indicate that wP-primed individuals maintain their Th1 polarization through this early memory interferon response. This suggests that stimulating the interferon pathway during vaccination could be an effective strategy to elicit a predominant Th1 response in aP-primed individuals that protects better against infection.