Lopez Christopher E, Zacharias Zeb R, Ross Kathleen A, Narasimhan Balaji, Waldschmidt Thomas J, Legge Kevin L
Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Interdisciplinary Immunology Graduate Program, Department of Pathology, University of Iowa, Iowa City, IA, USA.
NPJ Vaccines. 2024 May 31;9(1):96. doi: 10.1038/s41541-024-00883-3.
Influenza A virus (IAV) causes significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. The antigenic drift/shift of IAV continually gives rise to new strains and subtypes, aiding IAV in circumventing previously established immunity. As a result, there has been substantial interest in developing a broadly protective IAV vaccine that induces, durable immunity against multiple IAVs. Previously, a polyanhydride nanoparticle-based vaccine or nanovaccine (IAV-nanovax) encapsulating H1N1 IAV antigens was reported, which induced pulmonary B and T cell immunity and resulted in cross-strain protection against IAV. A key feature of IAV-nanovax is its ability to easily incorporate diverse proteins/payloads, potentially increasing its ability to provide broad protection against IAV and/or other pathogens. Due to human susceptibility to both H1N1 and H3N2 IAV, several H3N2 nanovaccines were formulated herein with multiple IAV antigens to examine the "plug-and-play" nature of the polyanhydride nanovaccine platform and determine their ability to induce humoral and cellular immunity and broad-based protection similar to IAV-nanovax. The H3N2-based IAV nanovaccine formulations induced systemic and mucosal B cell responses which were associated with antigen-specific antibodies. Additionally, systemic and lung-tissue resident CD4 and CD8 T cell responses were enhanced post-vaccination. These immune responses corresponded with protection against both homologous and heterosubtypic IAV infection. Overall, these results demonstrate the plug-and-play nature of the polyanhydride nanovaccine platform and its ability to generate immunity and protection against IAV utilizing diverse antigenic payloads.
甲型流感病毒（IAV）由于季节性流行和周期性大流行，在全球范围内导致了严重的发病率和死亡率。IAV的抗原漂移/转变不断产生新的毒株和亚型，有助于IAV规避先前建立的免疫力。因此，人们对开发一种能诱导针对多种IAV产生持久免疫力的广泛保护性IAV疫苗产生了浓厚兴趣。此前，有报道称一种基于聚酸酐纳米颗粒的疫苗或纳米疫苗（IAV-纳米疫苗），其包裹了H1N1 IAV抗原，可诱导肺部B细胞和T细胞免疫，并产生针对IAV的交叉毒株保护作用。IAV-纳米疫苗的一个关键特性是其能够轻松整合多种蛋白质/负载物，这可能增强其针对IAV和/或其他病原体提供广泛保护的能力。由于人类对H1N1和H3N2 IAV均易感，本文制备了几种含有多种IAV抗原的H3N2纳米疫苗，以研究聚酸酐纳米疫苗平台的“即插即用”特性，并确定它们诱导体液免疫和细胞免疫以及产生与IAV-纳米疫苗类似的广泛保护的能力。基于H3N2的IAV纳米疫苗制剂诱导了全身和黏膜B细胞反应，这些反应与抗原特异性抗体相关。此外，接种疫苗后全身和肺组织驻留的CD4和CD8 T细胞反应增强。这些免疫反应与针对同源和异源亚型IAV感染的保护作用相对应。总体而言，这些结果证明了聚酸酐纳米疫苗平台的即插即用特性及其利用多种抗原负载物产生针对IAV的免疫和保护作用的能力。
