Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, Animal Science College, Hebei North University, Zhangjiakou, 075131, Hebei, China.
The Animal Husbandry and Veterinary Institute of Hebei, Baoding, 071001, Hebei, China.
Virol J. 2023 Apr 21;20(1):76. doi: 10.1186/s12985-023-02044-9.
H9N2 virus is mainly transmitted through the respiratory mucosal pathway, so mucosal immunity is considered to play a good role in controlling avian influenza infection. It is commonly accepted that no adequate mucosal immunity is achieved by inactivated vaccines, which was widely used to prevent and control avian influenza virus infection. Thus, an improved vaccine to induce both mucosal immunity and systemic immunity is urgently required to control H9N2 avian influenza outbreaks in poultry farms.
In this study, we constructed a novel Lactococcus lactis (L. lactis) strain expressing a recombinant fusion protein consisting of the HA1 proteins derived from an endemic H9N2 virus strain and chicken IgY Fc fragment. We evaluated the immunogenicity and protective efficacy of this recombinant L. lactis HA1-Fc strain.
Our data demonstrated that chickens immunized with L. lactis HA1-Fc strain showed significantly increased levels of serum antibodies, mucosal secretory IgA, T cell-mediated immune responses, and lymphocyte proliferation. Furthermore, following challenge with H9N2 avian influenza virus, chickens immunized with L. lactis HA1-Fc strain showed reduced the weight loss, relieved clinical symptoms, and decreased the viral titers and the pathological damage in the lung. Moreover, oropharyngeal and cloacal shedding of the H9N2 influenza virus was detected in chicken immunized with L. lactis HA1-Fc after infection, the results showed the titer was low and reduced quickly to reach undetectable levels at 7 days after infection.
Our data showed that the recombinant L. lactis HA1-Fc strain could induce protective mucosal and systemic immunity, and this study provides a theoretical basis for improving immune responses to prevent and control H9N2 virus infection.
H9N2 病毒主要通过呼吸道黏膜途径传播,因此黏膜免疫被认为在控制流感感染方面发挥着良好的作用。人们普遍认为,灭活疫苗不能产生足够的黏膜免疫,而这种疫苗曾被广泛用于预防和控制禽流感病毒感染。因此,迫切需要开发一种能够诱导黏膜免疫和系统免疫的改良疫苗,以控制家禽养殖场中 H9N2 禽流感的爆发。
在本研究中,我们构建了一种新型的乳球菌(Lactococcus lactis,L. lactis)菌株,该菌株表达了一种由地方性 H9N2 病毒株的 HA1 蛋白和鸡 IgY Fc 片段组成的重组融合蛋白。我们评估了该重组 L. lactis HA1-Fc 菌株的免疫原性和保护效力。
我们的数据表明,用 L. lactis HA1-Fc 菌株免疫的鸡表现出显著增加的血清抗体、黏膜分泌型 IgA、T 细胞介导的免疫反应和淋巴细胞增殖。此外,在用 H9N2 禽流感病毒攻毒后,用 L. lactis HA1-Fc 菌株免疫的鸡体重减轻减轻,临床症状缓解,病毒滴度和肺部病理损伤减少。此外,在感染后用 L. lactis HA1-Fc 免疫的鸡中检测到了 H9N2 流感病毒的口咽和泄殖腔脱落,但结果表明其滴度较低,并迅速减少,在感染后 7 天达到无法检测的水平。
我们的数据表明,重组 L. lactis HA1-Fc 菌株能够诱导保护性黏膜和系统免疫,为改善免疫反应以预防和控制 H9N2 病毒感染提供了理论依据。