Department of Biology and Microbiology, South Dakota State University, Brookings, SD, 57007, USA; China Institute of Veterinary Drug Control, 8 Zhongguancun S St, Beijing, China.
Department of Biology and Microbiology, South Dakota State University, Brookings, SD, 57007, USA.
Vet Microbiol. 2019 Jan;228:26-31. doi: 10.1016/j.vetmic.2018.11.008. Epub 2018 Nov 16.
There is an urgent need to develop a broad-spectrum vaccine that can effectively prevent or eliminate the spread of co-circulating swine influenza virus strains in multiple lineages or subtypes. We describe here that pre-exposure with a live virus generated via a A/WSN/1933(H1N1) reverse genetics system resulted in a significant reduction of viral shedding from pigs exposed to either a swine H1N1 virus or a swine H3N2 virus. At 3-day post challenge (DPC), approximately 1 log and 1.5 logs reductions of viral shedding were observed in the swine H1N1- and H3N2-challenged vaccinated pigs when compared to unvaccinated animals. A further decline in viral load was observed at 5 DPC where viral shedding was decreased by greater than 3 logs in vaccinated pigs receiving either the H1N1 or H3N2 virus challenge. Although the sera of the vaccinated pigs contained high titers of neutralizing antibodies against the vaccine strain, measured by Hemagglutination Inhibition (HI) assay, only suboptimal HI titers of neutralizing antibody were detected in the post-challenge serum of the vaccinated animals using the challenge swine H1N1 virus. The substantial genetic and antigenic differences between the vaccine virus and the challenge viruses imply that the observed protection may be mediated by mechanisms other than neutralization by IgG, such as non-neutralizing antibody activities, mucosal immunity, or conserved T cell immunity, which warrants further investigation.
目前迫切需要开发一种广谱疫苗，以有效预防或消除多种谱系或亚型共循环的猪流感病毒株的传播。我们在这里描述了，通过 A/WSN/1933(H1N1)反向遗传系统生成的活病毒进行预先暴露，可显著减少暴露于猪流感 H1N1 病毒或猪 H3N2 病毒的猪的病毒脱落。在攻毒后 3 天（DPC），与未接种疫苗的动物相比，接种疫苗的猪在猪 H1N1-和 H3N2-攻毒后，病毒脱落量分别减少了约 1 个对数和 1.5 个对数。在 5 DPC 时，病毒载量进一步下降，接种猪在接受 H1N1 或 H3N2 病毒攻毒后，病毒脱落减少了 3 个以上对数。尽管接种猪的血清中含有针对疫苗株的高滴度中和抗体，通过血凝抑制（HI）测定法测量，但在用攻毒猪 H1N1 病毒检测接种动物的攻毒后血清时，仅检测到中和抗体的 HI 效价不理想。疫苗病毒与攻毒病毒之间存在显著的遗传和抗原差异，这意味着观察到的保护作用可能是由中和 IgG 以外的机制介导的，例如非中和抗体活性、黏膜免疫或保守的 T 细胞免疫，这值得进一步研究。
