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

Lisa Willemsen, Jiyeun Lee, Pramod Shinde, Ferran Soldevila, Minori Aoki, Shelby Orfield, Mari Kojima, Ricardo Silva Antunes, Alessandro Sette and Bjoern Peters ()
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Lisa Willemsen: La Jolla Institute for Immunology
Jiyeun Lee: La Jolla Institute for Immunology
Pramod Shinde: La Jolla Institute for Immunology
Ferran Soldevila: La Jolla Institute for Immunology
Minori Aoki: La Jolla Institute for Immunology
Shelby Orfield: La Jolla Institute for Immunology
Mari Kojima: La Jolla Institute for Immunology
Ricardo Silva Antunes: La Jolla Institute for Immunology
Alessandro Sette: La Jolla Institute for Immunology
Bjoern Peters: La Jolla Institute for Immunology

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: 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, 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.

Date: 2025
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DOI: 10.1038/s41467-025-58460-8

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