Ma Yao, Dong Chunhong, Kim Joo Kyung, Zhu Wandi, Wei Lai, Wang Ye, Kang Sang-Moo, Wang Bao-Zhong
Center for Inflammation, Immunity & Infection, Georgia State University Institute for Biomedical Sciences, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.
Center for Inflammation, Immunity & Infection, Georgia State University Institute for Biomedical Sciences, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.
Vaccine. 2025 Feb 6;46:126670. doi: 10.1016/j.vaccine.2024.126670. Epub 2024 Dec 27.
The immune memory imprinted during an individual's initial influenza exposure (influenza imprinting) has long-lasting effects on the host's response to subsequent influenza infections and vaccinations. Here, we investigate how different influenza virus imprinting impacts the immune responses to subunit, inactivated virus, and protein-based nanoparticle vaccines in Balb/c mice. Our results indicated a phylogenetic distance-dependent effect of influenza imprinting on subunit hemagglutinin (HA) or formalin-inactivated (FI) virus vaccine immunizations. Aichi (H3N2, group 2) HA (HA3) or FI-Aichi vaccination in mice imprinted with closely related Phili (H3N2) triggered significant Aichi-specific HAI antibody and balanced HA3-specific Th1/Th2 antibody immune responses, resulting in robust protection against Aichi. In contrast, HA3 vaccination in PR8 (H1N1, group 1) imprinted mice (PR8-2HA3) induced Th2-leaning responses comparable to those observed in mice without prior influenza immune imprinting (PBS-2HA3). However, subsequent heterosubtypic infections and vaccinations eliminated such effects on antibody subtype profiles. Nonetheless, initial virus exposure established a long-lasting capacity to produce HAI antibody responses against the imprinting strains. Moreover, Phili imprinting followed by HA3/NP nanocluster vaccination protected mice from Aichi infections and induced enhanced cross-reactive immunity. Our study highlights the significance of considering an individual's influenza exposure history when designing and evaluating the effectiveness of influenza vaccines.
个体初次接触流感病毒时形成的免疫记忆（流感印记）对宿主随后对流感感染和疫苗接种的反应具有持久影响。在此，我们研究了不同的流感病毒印记如何影响Balb/c小鼠对亚单位疫苗、灭活病毒疫苗和基于蛋白质的纳米颗粒疫苗的免疫反应。我们的结果表明，流感印记对亚单位血凝素（HA）或福尔马林灭活（FI）病毒疫苗免疫具有系统发育距离依赖性效应。在用密切相关的菲律宾株（H3N2）印记的小鼠中接种爱知株（H3N2，第2组）HA（HA3）或FI-爱知疫苗，引发了显著的爱知特异性血凝抑制（HAI）抗体以及平衡的HA3特异性Th1/Th2抗体免疫反应，从而对爱知株产生了强大的保护作用。相比之下，在PR8（H1N1，第1组）印记小鼠（PR8-2HA3）中接种HA3疫苗诱导的Th2偏向性反应与未进行过流感免疫印记的小鼠（PBS-2HA3）中观察到的反应相当。然而，随后的异亚型感染和疫苗接种消除了对抗体亚型谱的这种影响。尽管如此，初次病毒暴露建立了针对印记毒株产生HAI抗体反应的持久能力。此外，先用菲律宾株印记，随后接种HA3/核蛋白（NP）纳米簇疫苗可保护小鼠免受爱知株感染，并诱导增强的交叉反应性免疫。我们的研究强调了在设计和评估流感疫苗有效性时考虑个体流感暴露史的重要性。
