Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Immunol. 2020 Jun 9;11:1166. doi: 10.3389/fimmu.2020.01166. eCollection 2020.
Conventional influenza vaccines aim at the induction of virus-neutralizing antibodies that provide with sterilizing immunity. However, influenza vaccination often confers protection from disease but not from infection. The impact of infection-permissive vaccination on the immune response elicited by subsequent influenza virus infection is not well-understood. Here, we investigated to what extent infection-permissive immunity, in contrast to virus-neutralizing immunity, provided by a trivalent inactivated virus vaccine (TIV) modulates disease and virus-induced host immune responses after sublethal vaccine-matching H1N1 infection in a mouse model. More than one TIV vaccination was needed to induce a serum HI titer and provide sterilizing immunity upon homologous virus infection. However, single TIV administration provided infection-permissive immunity, characterized by lower viral lung titers and faster recovery. Despite the presence of replicating virus, single TIV vaccination prevented induction of pro-inflammatory cyto- and chemokines, alveolar macrophage depletion as well as the establishment of lung-resident B and T cells after infection. To investigate virus infection-induced cross-protective heterosubtypic immune responses in vaccinated and unvaccinated animals, mice were re-infected with a lethal dose of H3N2 virus 4 weeks after H1N1 infection. Single TIV vaccination did not prevent H1N1 virus infection-induced heterosubtypic cross-protection, but shifted the mechanism of cross-protection from the cellular to the humoral branch of the immune system. These results suggest that suboptimal vaccination with conventional influenza vaccines may still positively modulate disease outcome after influenza virus infection, while promoting humoral heterosubtypic immunity after virus infection.
传统的流感疫苗旨在诱导产生能够提供杀菌免疫的病毒中和抗体。然而，流感疫苗接种通常只能提供对疾病的保护，而不能提供对感染的保护。感染许可性疫苗接种对随后流感病毒感染引起的免疫反应的影响尚不清楚。在这里，我们研究了在亚致死性疫苗匹配的 H1N1 感染的小鼠模型中，与病毒中和免疫相比，三价灭活病毒疫苗（TIV）提供的感染许可性免疫在多大程度上调节疾病和病毒引起的宿主免疫反应。需要多次 TIV 接种才能诱导血清 HI 滴度并在同源病毒感染时提供杀菌免疫。然而，单次 TIV 给药可提供感染许可性免疫，其特征是病毒肺部滴度较低且恢复较快。尽管存在复制病毒，但单次 TIV 接种可防止诱导促炎细胞因子和趋化因子、肺泡巨噬细胞耗竭以及感染后肺驻留 B 和 T 细胞的建立。为了研究接种和未接种动物中病毒感染诱导的交叉保护异源免疫反应，在 H1N1 感染后 4 周，用致死剂量的 H3N2 病毒重新感染小鼠。单次 TIV 接种不能预防 H1N1 病毒感染诱导的异源交叉保护，但将交叉保护的机制从细胞免疫转移到了体液免疫。这些结果表明，传统流感疫苗的不完全接种在流感病毒感染后仍可能积极调节疾病结局，同时在病毒感染后促进体液异源免疫。
