Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Immunol. 2019 Aug 21;10:2005. doi: 10.3389/fimmu.2019.02005. eCollection 2019.
Seasonal influenza viruses cause significant morbidity and mortality in the global population every year. Although seasonal vaccination limits disease, mismatches between the circulating strain and the vaccine strain can severely impair vaccine effectiveness. Because of this, there is an urgent need for a universal vaccine that induces broad protection against drifted seasonal and emerging pandemic influenza viruses. Targeting the conserved stalk region of the influenza virus hemagglutinin (HA), the major glycoprotein on the surface of the virus, results in the production of broadly protective antibody responses. Furthermore, replication deficient viral vectors based on Chimpanzee Adenovirus Oxford 1 (ChAdOx1) and modified vaccinia Ankara (MVA) virus expressing the influenza virus internal antigens, the nucleoprotein (NP) and matrix 1 (M1) protein, can induce strong heterosubtypic influenza virus-specific T cell responses in vaccinated individuals. Here, we combine these two platforms to evaluate the efficacy of a viral vectored vaccination regimen in protecting ferrets from H3N2 influenza virus infection. We observed that viral vectored vaccines expressing both stalk-targeting, chimeric HA constructs, and the NP+M1 fusion protein, in a prime-boost regimen resulted in the production of antibodies toward group 2 HAs, the HA stalk, NP and M1, as well as in induction of influenza virus-specific-IFNγ responses. The immune response induced by this vaccination regime ultimately reduced viral titers in the respiratory tract of influenza virus infected ferrets. Overall, these results improve our understanding of vaccination platforms capable of harnessing both cellular and humoral immunity with the goal of developing a universal influenza virus vaccine.
季节性流感病毒每年都会在全球人群中导致大量发病和死亡。尽管季节性疫苗接种可以限制疾病的发生,但循环株与疫苗株之间的不匹配会严重降低疫苗的有效性。因此,迫切需要一种通用疫苗,以诱导对漂移的季节性和新兴大流行性流感病毒的广泛保护。针对流感病毒血凝素(HA)的保守茎部区域,即病毒表面的主要糖蛋白,可产生广泛的保护性抗体反应。此外,基于 chimpanzee adenovirus oxford 1(ChAdOx1)和修饰的痘苗 Ankara(MVA)病毒的复制缺陷型病毒载体,表达流感病毒内部抗原核蛋白(NP)和基质 1(M1)蛋白,可在接种个体中诱导强烈的异源流感病毒特异性 T 细胞反应。在这里,我们将这两种平台结合起来,评估病毒载体疫苗接种方案在保护雪貂免受 H3N2 流感病毒感染方面的功效。我们观察到,在初免-加强方案中,表达茎靶向嵌合 HA 构建体和 NP+M1 融合蛋白的病毒载体疫苗可诱导针对 2 组 HA、HA 茎、NP 和 M1 的抗体产生,并诱导流感病毒特异性 IFNγ 反应。这种免疫反应最终降低了感染流感病毒的雪貂呼吸道中的病毒滴度。总之,这些结果提高了我们对能够利用细胞和体液免疫的疫苗平台的理解,以期开发通用流感病毒疫苗。
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