Petro-Turnquist Erika, Madapong Adthakorn, Steffen David, Weaver Eric A
Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Nebraska Veterinary Diagnostics Center, Lincoln, NE 68583, USA.
Vaccines (Basel). 2024 Aug 22;12(8):943. doi: 10.3390/vaccines12080943.
Swine influenza A virus (IAV-S) is a highly prevalent and transmissible pathogen infecting worldwide swine populations. Our previous work has shown that the computationally derived vaccine platform, Epigraph, can induce broadly cross-reactive and durable immunity against H3 IAV-S in mice and swine. Therefore, in this study, we assess the immunogenicity and protective efficacy of the Epigraph vaccine at increasingly lower doses to determine the minimum dose required to maintain protective immunity against three genetically divergent H3 IAV-S. We assessed both antibody and T cell responses and then challenged with three H3N2 IAV-S derived from either Cluster IV(A), Cluster I, or the 2010.1 "human-like" cluster and assessed protection through reduced pathology, reduced viral load in the lungs, and reduced viral shedding from nasal swabs. Overall, we observed a dose-dependent effect where the highest dose of Epigraph protected against all three challenges, the middle dose of Epigraph protected against more genetically similar IAV-S, and the lowest dose of Epigraph only protected against genetically similar IAV-S. The results of these studies can be used to continue developing a broadly protective and low-dose vaccine against H3 IAV-S.
甲型流感病毒（IAV-S）是一种在全球猪群中高度流行且具有传染性的病原体。我们之前的研究表明，通过计算机设计的疫苗平台Epigraph能够在小鼠和猪体内诱导出针对H3 IAV-S的广泛交叉反应性和持久免疫力。因此，在本研究中，我们评估了Epigraph疫苗在越来越低剂量下的免疫原性和保护效力，以确定维持针对三种基因不同的H3 IAV-S的保护性免疫所需的最低剂量。我们评估了抗体和T细胞反应，然后用源自IV(A)簇、I簇或2010.1“类人”簇的三种H3N2 IAV-S进行攻毒，并通过减轻病理变化、降低肺部病毒载量以及减少鼻拭子中的病毒脱落来评估保护效果。总体而言，我们观察到了剂量依赖性效应，即Epigraph的最高剂量对所有三种攻毒都有保护作用，中等剂量对基因更相似的IAV-S有保护作用，而Epigraph的最低剂量仅对基因相似的IAV-S有保护作用。这些研究结果可用于继续研发针对H3 IAV-S的广泛保护性低剂量疫苗。
