Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Pan Genome Systems, Madison, Wisconsin, USA.
J Virol. 2020 Sep 15;94(19). doi: 10.1128/JVI.01016-20.
Infectious bronchitis (IB) caused by infectious bronchitis virus (IBV) is currently a major threat to chicken health, with multiple outbreaks being reported in the United States over the past decade. Modified live virus (MLV) vaccines used in the field can persist and provide the genetic material needed for recombination and emergence of novel IBV serotypes. Inactivated and subunit vaccines overcome some of the limitations of MLV with no risk of virulence reversion and emergence of new virulent serotypes. However, these vaccines are weakly immunogenic and poorly protective. There is an urgent need to develop more effective vaccines that can elicit a robust, long-lasting immune response. In this study, we evaluate a novel adjuvant system developed from Quil-A and chitosan (QAC) for the intranasal delivery of nucleic acid immunogens to improve protective efficacy. The QAC adjuvant system forms nanocarriers (<100 nm) that efficiently encapsulate nucleic acid cargo, exhibit sustained release of payload, and can stably transfect cells. Encapsulation of plasmid DNA vaccine expressing IBV nucleocapsid (N) protein by the QAC adjuvant system (pQAC-N) enhanced immunogenicity, as evidenced by robust induction of adaptive humoral and cellular immune responses postvaccination and postchallenge. Birds immunized with pQAC-N showed reduced clinical severity and viral shedding postchallenge on par with protection observed with current commercial vaccines without the associated safety concerns. Presented results indicate that the QAC adjuvant system can offer a safer alternative to the use of live vaccines against avian and other emerging coronaviruses. According to 2017 U.S. agriculture statistics, the combined value of production and sales from broilers, eggs, turkeys, and chicks was $42.8 billion. Of this number, broiler sales comprised 67% of the industry value, with the production of >50 billion pounds of chicken meat. The economic success of the poultry industry in the United States hinges on the extensive use of vaccines to control infectious bronchitis virus (IBV) and other poultry pathogens. The majority of vaccines currently licensed for poultry health include both modified live vaccine and inactivated pathogens. Despite their proven efficacy, modified live vaccine constructs take time to produce and could revert to virulence, which limits their safety. The significance of our research stems from the development of a safer and potent alternative mucosal vaccine to replace live vaccines against IBV and other emerging coronaviruses.
传染性支气管炎（IB）是由传染性支气管炎病毒（IBV）引起的，目前是鸡健康的主要威胁，在过去十年中，美国多次报告爆发该病。田间使用的活病毒（MLV）疫苗可以持续存在，并为重组和新型 IBV 血清型的出现提供所需的遗传物质。灭活疫苗和亚单位疫苗克服了 MLV 的一些局限性，不存在毒力返祖和出现新的强毒血清型的风险。然而，这些疫苗的免疫原性较弱，保护效果不佳。因此，迫切需要开发更有效的疫苗，以产生强大、持久的免疫反应。在这项研究中，我们评估了一种由 Quil-A 和壳聚糖（QAC）开发的新型佐剂系统，用于经鼻腔递送核酸免疫原，以提高保护效力。QAC 佐剂系统形成纳米载体（<100nm），可有效包裹核酸货物，持续释放有效载荷，并可稳定转染细胞。用 QAC 佐剂系统（pQAC-N）包封表达 IBV 核衣壳（N）蛋白的质粒 DNA 疫苗增强了免疫原性，正如接种后和攻毒后适应性体液和细胞免疫反应的强烈诱导所证明的那样。用 pQAC-N 免疫的鸡在攻毒后临床严重程度和病毒脱落均降低，与当前商业疫苗相当，且没有相关的安全问题。结果表明，与使用活疫苗针对禽和其他新兴冠状病毒相比，QAC 佐剂系统可以提供更安全的替代方案。根据 2017 年美国农业统计数据，肉鸡、鸡蛋、火鸡和雏鸡的生产和销售总价值为 428 亿美元。在这个数字中，肉鸡销售额占行业价值的 67%，生产了超过 500 亿磅鸡肉。美国家禽业的经济成功取决于广泛使用疫苗来控制传染性支气管炎病毒（IBV）和其他家禽病原体。目前批准用于家禽健康的疫苗包括活疫苗和灭活病原体。尽管这些疫苗已被证明有效，但活疫苗构建体需要时间来生产，并且可能恢复毒力，这限制了它们的安全性。我们研究的意义在于开发一种更安全、更有效的黏膜疫苗来替代针对 IBV 和其他新兴冠状病毒的活疫苗。
