Hockman Megan, Matthews Julia, Carlock Michael A, Ross Ted M, Gresham David, Ghedin Elodie
Center for Genomics and Systems Biology, New York University, New York, New York, USA.
Systems Genomics Section, Laboratory of Parasitic Diseases, DIR, NIAID, NIH, Bethesda, Maryland, USA.
Microbiol Spectr. 2025 Aug 5;13(8):e0335424. doi: 10.1128/spectrum.03354-24. Epub 2025 Jun 23.
The effectiveness of the seasonal influenza vaccine varies between individuals. Specific risk groups with comorbidities, such as the obese, have an increased risk of infection even when vaccinated. It has been proposed that a heightened baseline inflammatory state and alterations in adaptive immune cell populations in obese individuals may adversely impact immune responses to pathogens and vaccines. Therefore, understanding differences in vaccine responses in obese individuals is critical for the development of improved influenza vaccine design and strategies. Previously, we identified a transcriptomic signature prior to seasonal influenza vaccination that is predictive of an individual's response to the influenza vaccine. To understand the dynamics of host responses following vaccination, we studied systemic gene expression from whole blood collected from 163 vaccinated individuals on days 3, 7, and 28 post-vaccination. Gene expression profiles were compared between high and low vaccine responders in both obese and non-obese groups. We detected characteristic changes in gene expression over time, with a peak at day 7 post-vaccination. A large subset of genes associated with the adaptive immune response exhibited significantly different expressions in high responders and non-responders to the vaccine. Distinct gene sets presented differing temporal patterns in different weight and response groups, indicative of molecular processes impacting the immune response to vaccination.
This study yields insights into how co-morbidities, such as obesity, impact the immune response to the seasonal influenza vaccine. By analyzing blood samples collected days and weeks after the vaccination of a cohort of subjects, we can examine changes in gene expression over time and how those changes are similar or different depending on risk factors. This provides clues into potential molecular mechanisms behind an effective immune response to vaccination.
季节性流感疫苗的有效性因人而异。患有合并症的特定风险群体，如肥胖者，即使接种了疫苗，感染风险也会增加。有人提出，肥胖个体基线炎症状态增强以及适应性免疫细胞群体改变可能会对病原体和疫苗的免疫反应产生不利影响。因此，了解肥胖个体疫苗反应的差异对于改进流感疫苗设计和策略的开发至关重要。此前，我们确定了季节性流感疫苗接种前的转录组特征，该特征可预测个体对流感疫苗的反应。为了了解接种疫苗后宿主反应的动态变化，我们研究了163名接种疫苗个体在接种后第3天、第7天和第28天采集的全血中的系统基因表达。比较了肥胖组和非肥胖组中高疫苗反应者和低疫苗反应者之间的基因表达谱。我们检测到基因表达随时间的特征性变化，在接种后第7天达到峰值。与适应性免疫反应相关的一大组基因在疫苗高反应者和无反应者中表现出显著不同的表达。不同的基因集在不同体重和反应组中呈现出不同的时间模式，表明分子过程影响了对疫苗接种的免疫反应。
本研究深入了解了肥胖等合并症如何影响对季节性流感疫苗的免疫反应。通过分析一组受试者接种疫苗数天和数周后采集的血样，我们可以研究基因表达随时间的变化，以及这些变化如何因风险因素而相似或不同。这为有效疫苗接种免疫反应背后的潜在分子机制提供了线索。
