Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA; Pan Genome Systems, Madison, WI, USA.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
Vaccine. 2019 Aug 14;37(35):5051-5058. doi: 10.1016/j.vaccine.2019.06.077. Epub 2019 Jul 9.
Avian influenza virus (AIV) is an extraordinarily diverse pathogen that causes significant morbidity in domesticated poultry populations and threatens human life with looming pandemic potential. Controlling avian influenza in susceptible populations requires highly effective, economical and broadly reactive vaccines. Several AIV vaccines have proven insufficient despite their wide use, and better technologies are needed to improve their immunogenicity and broaden effectiveness. Previously, we developed a "mosaic" H5 subtype hemagglutinin (HA) AIV vaccine and demonstrated its broad protection against diverse highly pathogenic H5N1 and seasonal H1N1 virus strains in mouse and non-human primate models. There is a significant interest in developing effective and safe vaccines against AIV that cannot contribute to the emergence of new strains of the virus once circulating in poultry. Here, we report on the development of an H5 mosaic (H5M) vaccine antigen formulated with polyanhydride nanoparticles (PAN) that provide sustained release of encapsulated antigens. H5M vaccine constructs were immunogenic whether delivered by the modified virus Ankara (MVA) strain or encapsulated within PAN. Both humoral and cellular immune responses were generated in both specific-pathogen free (SPF) and commercial chicks. Importantly, chicks vaccinated by H5M constructs were protected in terms of viral shedding from divergent challenge with a low pathogenicity avian influenza (LPAI) strain at 8 weeks post-vaccination. In addition, protective levels of humoral immunity were generated against highly pathogenic avian influenza (HPAI) of the similar H5N1 and genetically dissimilar H5N2 viruses. Overall, the developed platform technologies (MVA vector and PAN encapsulation) were safe and provided high levels of sustained protection against AIV in chickens. Such approaches could be used to design more efficacious vaccines against other important poultry infections.
禽流感病毒（AIV）是一种非常多样化的病原体，它会导致家禽群体中出现大量的疾病，并有可能引发大流行，从而威胁到人类的生命。控制易感人群中的禽流感需要高度有效、经济和广泛反应的疫苗。尽管已经广泛使用了几种 AIV 疫苗，但它们的效果并不理想，因此需要更好的技术来提高它们的免疫原性并扩大其有效性。此前，我们开发了一种“嵌合”H5 亚型血凝素（HA）AIV 疫苗，并在小鼠和非人类灵长类动物模型中证明了其对多种高致病性 H5N1 和季节性 H1N1 病毒株的广泛保护作用。人们非常希望开发针对 AIV 的有效和安全疫苗，这些疫苗不能在病毒在禽类中传播后导致新病毒株的出现。在这里，我们报告了一种 H5 嵌合（H5M）疫苗抗原的开发，该抗原采用聚酸酐纳米粒子（PAN）进行配方，可提供包封抗原的持续释放。无论通过改良的病毒安卡拉（MVA）株还是封装在 PAN 内，H5M 疫苗构建体都具有免疫原性。无论是在无特定病原体（SPF）鸡还是商业鸡中，都产生了体液和细胞免疫反应。重要的是，接种 H5M 构建体的雏鸡在接种后 8 周用低致病性禽流感（LPAI）株进行的不同挑战中，在病毒脱落方面得到了保护。此外，还针对类似 H5N1 和遗传上不同的 H5N2 病毒的高致病性禽流感（HPAI）产生了保护性水平的体液免疫。总体而言，所开发的平台技术（MVA 载体和 PAN 封装）是安全的，并为鸡提供了针对 AIV 的高水平持续保护。这些方法可用于设计针对其他重要家禽感染的更有效的疫苗。
