Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Department of Veterinary and Biomedical Sciences, Animal Disease Research And Diagnostic Laboratory, South Dakota State University, Brookings, SD, United States.
Front Immunol. 2021 Nov 5;12:747574. doi: 10.3389/fimmu.2021.747574. eCollection 2021.
Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses challenges to public health given its zoonotic potential. Thus effective IAV-S vaccines are needed and highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs, with higher levels of neutralizing antibodies (NA) being detected in OV-HA-NP-immunized animals pre-challenge infection. Although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S-specific proliferating CD8+ T cells upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in incremental protection against challenge infection as evidenced by a reduced secondary antibody response (NA and HI antibodies) following IAV-S challenge and reduced virus shedding in nasal secretions (lower viral RNA loads and frequency of animals shedding viral RNA and infectious virus), when compared to animals in the OV-HA group. Interestingly, broader cross neutralization activity was also observed in serum of OV-HA-NP-immunized animals against a panel of contemporary IAV-S isolates representing the major genetic clades circulating in swine. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.
猪流感是由甲型流感病毒（IAV-S）引起的猪的一种高度传染性呼吸道疾病。IAV-S 因其人畜共患的潜力对养猪业造成了重大经济损失，并对公共卫生构成了挑战。因此，需要有效的 IAV-S 疫苗，这是非常理想的，将有益于动物和人类的健康。在这里，我们开发了两种表达血凝素（HA）基因的重组 ORF 病毒（OV-HA）或 IAV-S 的 HA 和核蛋白（NP）基因（OV-HA-NP）。在猪中评估了这两种重组病毒的免疫原性和保护效力。OV-HA 和 OV-HA-NP 重组病毒均在猪中引发了强烈的病毒中和抗体反应，在预挑战感染前，OV-HA-NP 免疫动物中检测到更高水平的中和抗体（NA）。尽管两种重组病毒均引发了 IAV-S 特异性 T 细胞反应，但在 OV-HA-NP 免疫动物中，再刺激时 IAV-S 特异性增殖 CD8+T 细胞的频率高于 OV-HA 组。重要的是，IgG1/IgG2 型 ELISA 显示，用 OV-HA 免疫诱导了 Th2 偏向的免疫反应，而用 OV-HA-NP 病毒免疫则导致了 Th1 偏向的免疫反应。与未免疫对照相比，用 OV-HA 或 OV-HA-NP 免疫的猪得到了保护，但与 OV-HA 组相比，用 OV-HA-NP 免疫导致了对挑战感染的增量保护，这表现在 IAV-S 挑战后二次抗体反应（NA 和 HI 抗体）降低，鼻分泌物中的病毒脱落减少（病毒 RNA 载量和脱落病毒 RNA 和传染性病毒的动物频率降低）。有趣的是，在 OV-HA-NP 免疫动物的血清中还观察到针对一组代表在猪中循环的主要遗传谱系的当代 IAV-S 分离株的更广泛的交叉中和活性。本研究证明了基于 ORFV 的载体在控制猪流感病毒方面的潜力。
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