PDF(Pubmed)
Abstract：
In this study, we pioneered an alternative technology for manufacturing subunit influenza hemagglutinin (HA)-based vaccines. This innovative method involves harnessing the pupae of the Lepidoptera Trichoplusia ni (T. ni) as natural biofactories in combination with baculovirus vectors (using CrisBio® technology). We engineered recombinant baculoviruses encoding two versions of the HA protein (trimeric or monomeric) derived from a pandemic avian H7N1 virus A strain (A/chicken/Italy/5093/99). These were then used to infect T. ni pupae, resulting in the production of the desired recombinant antigens. The obtained HA proteins were purified using affinity chromatography, consistently yielding approximately 75 mg/L of insect extract. The vaccine antigen effectively immunized poultry, which were subsequently challenged with a virulent H7N1 avian influenza virus. Following infection, all vaccinated animals survived without displaying any clinical symptoms, while none of the mock-vaccinated control animals survived. The CrisBio®-derived antigens induced high titers of HA-specific antibodies in the vaccinated poultry, demonstrating hemagglutination inhibition activity against avian H7N1 and human H7N9 viruses. These results suggest that the CrisBio® technology platform has the potential to address major industry challenges associated with producing recombinant influenza subunit vaccines, such as enhancing production yields, scalability, and the speed of development, facilitating the global deployment of highly effective influenza vaccines.
摘要：
在这项研究中,我们开创了一种生产亚单位流感血凝素(HA)疫苗的替代技术.这种创新的方法涉及利用鳞翅目Trichoplusiani的p（T.ni)作为与杆状病毒载体结合的天然生物工厂(使用CrisBio®技术)。我们对重组杆状病毒进行了工程改造，该杆状病毒编码两种形式的HA蛋白（三聚体或单体），这些HA蛋白来自大流行的禽类H7N1病毒A株（A/chicken/Italy/5093/99）。然后这些被用来感染T.nip，导致产生所需的重组抗原。获得的HA蛋白使用亲和层析纯化,始终产生约75mg/L的昆虫提取物。疫苗抗原有效免疫家禽，随后受到强毒H7N1禽流感病毒的攻击。感染后,所有接种疫苗的动物都存活下来，没有表现出任何临床症状，而模拟疫苗接种的对照动物均未存活。CrisBio®衍生的抗原在接种疫苗的家禽中诱导高滴度的HA特异性抗体，证明对禽H7N1和人H7N9病毒的血凝抑制活性。这些结果表明，CrisBio®技术平台有可能解决与生产重组流感亚单位疫苗相关的主要行业挑战。例如提高产量，可扩展性，和发展的速度，促进全球部署高效流感疫苗。
