Willemsen Lisa, Lee Jiyeun, Shinde Pramod, Soldevila Ferran, Aoki Minori, Orfield Shelby, Kojima Mari, da Silva Antunes Ricardo, Sette Alessandro, Peters Bjoern
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.
Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Nat Commun. 2025 Apr 1;16(1):3132. doi: 10.1038/s41467-025-58460-8.
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.
尽管百日咳疫苗接种覆盖率很高，但百日咳博德特氏菌（BP）引发的百日咳疫情仍在持续，且自疫苗从全细胞BP（wP）疫苗转换为无细胞BP（aP）疫苗以来呈上升趋势。wP疫苗接种与更持久的保护性免疫以及诱导的Th1极化记忆T细胞反应相关。在这里，我们通过多组学方法分析了30名接种wP疫苗和31名接种aP疫苗的个体的免疫反应，并确定了破伤风类毒素、白喉类毒素和无细胞百日咳疫苗（Tdap）加强免疫前后T细胞极化的相关因素。我们发现，早期转录变化表明存在干扰素反应，随后血浆IFN-γ和干扰素诱导的趋化因子水平升高（在加强免疫后第1 - 3天达到峰值），这与第28天疫苗诱导的记忆T细胞反应的Th1极化相关性最佳。我们的研究表明，接种wP疫苗的个体通过这种早期记忆干扰素反应维持其Th1极化。这表明在疫苗接种期间刺激干扰素途径可能是一种有效的策略，可在接种aP疫苗的个体中引发主要的Th1反应，从而更好地预防感染。
