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bioRxiv · 10.1101/2024.08.05.606623

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

Willemsen, L.·Lee, J.·Shinde, P.·Soldevila, F.·Aoki, M.·Orfield, S.·Kojima, M.·Antunes, R. d. S.·Sette, A.·Peters, B.
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Abstract

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, a multi-omics approach was applied to profile 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 found that transcriptional changes indicating an interferon response on day 1 post-booster along with elevated plasma concentrations of IFN-{gamma} and interferon-induced chemokines that peaked at day 1-3 post-booster correlated best with the Th1 polarization of the vaccine-induced memory T cell response on day 28. Our studies suggest 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.

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Willemsen, L., Lee, J., Shinde, P., Soldevila, F., Aoki, M., Orfield, S., Kojima, M., Antunes, R. d. S., Sette, A., Peters, B.. 2024-08-07. Th1 polarization in Bordetella pertussis vaccine responses is maintained through a positive feedback loop. https://doi.org/10.1101/2024.08.05.606623

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