Debisarun Priya A, Röring Rutger J, Bulut Özlem, Ten Doesschate Thijs, van der Vaart Thomas W, Kumar Vinod, Lemmers Helga, Dijkstra Heidi, Janssen Axel B, Veerman Karin, Ter Heine Rob, van Crevel Reinout, Ten Oever Jaap, Joosten Leo Ab, Bonten Marc J, van Werkhoven Cornelis H, van de Wijgert Janneke Hhm, Netea Mihai G
Department of Medicine and Radboud Center for Infectious Diseases Radboud University Medical Center Nijmegen The Netherlands.
Department of Medical Microbiology, Infectious Diseases & Infection Prevention Maastricht University Medical Center Maastricht The Netherlands.
Clin Transl Immunology. 2025 Sep 11;14(9):e70047. doi: 10.1002/cti2.70047. eCollection 2025.
Chronic systemic inflammation can lead to metabolic, cardiovascular and neurodegenerative complications, but the factors influencing it are incompletely understood. In this study, we evaluated several factors, including Bacille Calmette-Guérin (BCG) and influenza vaccination, SARS-CoV-2 infection and sex, that may impact systemic inflammation as assessed by targeted inflammatory plasma proteome analysis in healthy individuals.
Participants were randomised to BCG or placebo vaccination at the start of the Dutch SARS-CoV-2 epidemic in March/April 2020. They reported their influenza vaccination status for the most recent influenza season. Twelve weeks after BCG or placebo vaccination, we assessed relative concentrations of 69 proteins in plasma of 357 individuals.
Both BCG and quadrivalent influenza vaccination were associated with overall trends towards reduced systemic inflammation in both sexes, but with a more pronounced effect in men. However, the impact on specific immunological proteins varied between BCG and influenza vaccinations. SARS-CoV-2 infection in the 12 weeks between randomisation and plasma sampling was also associated with overall trends towards reduced systemic inflammation, reaching significance for CXCL10 and TNF concentrations. Notably, individuals who had received BCG vaccination prior to SARS-CoV-2 infection did not exhibit this protein profile. Furthermore, elevated CXCL11 and OPG concentrations at 12 weeks were associated with subsequent respiratory symptoms during the additional 9 months of follow-up.
Our study revealed distinctive alterations in the plasma inflammation proteome associated with BCG vaccination, influenza vaccination, SARS-CoV-2 infection and sex. These findings are exploratory and hypothesis-generating and warrant further investigation in well-controlled longitudinal cohort studies.
慢性全身性炎症可导致代谢、心血管和神经退行性并发症，但影响其的因素尚未完全明确。在本研究中，我们评估了几种可能影响全身性炎症的因素，包括卡介苗（BCG）和流感疫苗接种、SARS-CoV-2感染及性别，这些因素通过对健康个体进行靶向炎症血浆蛋白质组分析来评估。
在2020年3月/4月荷兰SARS-CoV-2疫情开始时，参与者被随机分配接受卡介苗或安慰剂接种。他们报告了最近流感季节的流感疫苗接种情况。在卡介苗或安慰剂接种12周后，我们评估了357名个体血浆中69种蛋白质的相对浓度。
卡介苗和四价流感疫苗接种均与两性全身性炎症减轻的总体趋势相关，但对男性的影响更为显著。然而，卡介苗和流感疫苗对接种特异性免疫蛋白的影响有所不同。在随机分组至血浆采样的12周内感染SARS-CoV-2也与全身性炎症减轻的总体趋势相关，CXCL10和TNF浓度达到显著水平。值得注意的是，在SARS-CoV-2感染之前接种卡介苗的个体并未表现出这种蛋白质谱。此外，12周时CXCL11和OPG浓度升高与后续9个月随访期间的呼吸道症状相关。
我们的研究揭示了与卡介苗接种、流感疫苗接种、SARS-CoV-2感染和性别相关的血浆炎症蛋白质组的独特变化。这些发现具有探索性且能生成假设，值得在严格控制的纵向队列研究中进一步调查。
