Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA.
Department of Animal Sciences, Center for Food Animal Health, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA.
Viruses. 2023 Apr 18;15(4):994. doi: 10.3390/v15040994.
Influenza A viruses (IAV-S) belonging to the H1 subtype are endemic in swine worldwide. Antigenic drift and antigenic shift lead to a substantial antigenic diversity in circulating IAV-S strains. As a result, the most commonly used vaccines based on whole inactivated viruses (WIVs) provide low protection against divergent H1 strains due to the mismatch between the vaccine virus strain and the circulating one. Here, a consensus coding sequence of the full-length of HA from H1 subtype was generated in silico after alignment of the sequences from IAV-S isolates obtained from public databases and was delivered to pigs using the Orf virus (ORFV) vector platform. The immunogenicity and protective efficacy of the resulting ORFVconH1 recombinant virus were evaluated against divergent IAV-S strains in piglets. Virus shedding after intranasal/intratracheal challenge with two IAV-S strains was assessed by real-time RT-PCR and virus titration. Viral genome copies and infectious virus load were reduced in nasal secretions of immunized animals. Flow cytometry analysis showed that the frequency of T helper/memory cells, as well as cytotoxic T lymphocytes (CTLs), were significantly higher in the peripheral blood mononuclear cells (PBMCs) of the vaccinated groups compared to unvaccinated animals when they were challenged with a pandemic strain of IAV H1N1 (CA/09). Interestingly, the percentage of T cells was higher in the bronchoalveolar lavage of vaccinated animals in relation to unvaccinated animals in the groups challenged with a H1N1 from the gamma clade (OH/07). In summary, delivery of the consensus HA from the H1 IAV-S subtype by the parapoxvirus ORFV vector decreased shedding of infectious virus and viral load of IAV-S in nasal secretions and induced cellular protective immunity against divergent influenza viruses in swine.
甲型流感病毒(IAV-S)属于 H1 亚型,在全球范围内在猪中流行。抗原漂移和抗原转变导致循环 IAV-S 株的抗原多样性显著增加。因此,基于全灭活病毒(WIV)的最常用疫苗由于疫苗病毒株与流行株之间的不匹配,对不同的 H1 株提供的保护作用较低。在这里,通过对来自公共数据库的 IAV-S 分离株的序列进行比对,在计算机上生成了 H1 亚型 HA 的全长共识编码序列,并使用口疮病毒(ORFV)载体平台递送给猪。评估了源自 ORFVconH1 重组病毒对仔猪中不同的 IAV-S 株的免疫原性和保护效力。通过实时 RT-PCR 和病毒滴定评估了经鼻腔/气管内攻毒两种 IAV-S 株后的病毒脱落情况。免疫动物鼻腔分泌物中的病毒基因组拷贝数和感染性病毒载量降低。流式细胞术分析表明,与未接种动物相比,当用大流行性 IAV H1N1(CA/09)株攻毒时,接种组外周血单核细胞(PBMC)中的辅助/记忆 T 细胞和细胞毒性 T 淋巴细胞(CTL)的频率明显更高。有趣的是,与未接种动物相比,在接种组用来自伽马分支的 H1N1(OH/07)株攻毒时,接种动物的支气管肺泡灌洗液中的 T 细胞百分比更高。总之,通过副痘病毒 ORFV 载体传递来自 H1 IAV-S 亚型的共识 HA 减少了鼻分泌物中传染性病毒的脱落和 IAV-S 的病毒载量,并诱导了针对猪中不同流感病毒的细胞保护性免疫。