Center for Vaccines and Immunology, University of Georgia, Athens, Georgia, USA.
Department of Infection Biology, Lehner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
J Virol. 2024 Sep 17;98(9):e0035424. doi: 10.1128/jvi.00354-24. Epub 2024 Aug 22.
Development of next-generation influenza virus vaccines is crucial to improve protection against circulating and emerging viruses. Current vaccine formulations have to be updated annually due to mutations in seasonal strains and do not offer protection against strains with pandemic potential. Computationally optimized broadly reactive antigen (COBRA) methodology has been utilized by our group to generate broadly reactive immunogens for individual influenza subtypes, which elicit protective immune responses against a broad range of strains over numerous seasons. Octavalent mixtures of COBRA hemagglutinin (HA) (H1, H2, H3, H5, H7, and influenza B virus) plus neuraminidase (NA) (N1 and N2) recombinant proteins mixed with c-di-AMP adjuvant were administered intranasally to naive or pre-immune ferrets in prime-boost fashion. Four weeks after final vaccination, collected sera were analyzed for breadth of antibody response, and the animals were challenged with seasonal or pre-pandemic strains. The octavalent COBRA vaccine elicited antibodies that recognized a broad panel of strains representing different subtypes, and these vaccinated animals were protected against influenza virus challenges. Overall, this study demonstrated that the mixture of eight COBRA HA/NA proteins mixed with an intranasal adjuvant is a promising candidate for a universal influenza vaccine.
Influenza is a respiratory virus which infects around a billion people globally every year, with millions experiencing severe illness. Commercial vaccine efficacy varies year to year and can be low due to mismatch of circulating virus strains. Thus, the formulation of current vaccines has to be adapted accordingly every year. The development of a broadly reactive influenza vaccine would lessen the global economic and public health burden caused by the different types of influenza viruses. The significance of our research is producing a promising universal vaccine candidate which provides protection against a wider range of virus strains over a wider range of time.
开发下一代流感病毒疫苗对于提高对流行和新兴病毒的保护至关重要。由于季节性毒株的突变，当前的疫苗配方每年都需要更新，并且不能针对具有大流行潜力的毒株提供保护。我们的小组利用计算优化的广谱反应性抗原（COBRA）方法，为各个流感亚型生成了广谱反应性免疫原，这些免疫原在多个季节对广泛的毒株产生了保护性免疫反应。八价 COBRA 血凝素（HA）（H1、H2、H3、H5、H7 和乙型流感病毒）和神经氨酸酶（NA）（N1 和 N2）重组蛋白与 c-di-AMP 佐剂的混合物以鼻内方式施用于初免或预免疫雪貂进行加强免疫。最后一次接种后 4 周，收集血清分析抗体反应的广度，并用季节性或大流行前毒株对动物进行攻毒。八价 COBRA 疫苗诱导的抗体可识别代表不同亚型的广泛的株系，这些接种疫苗的动物可免受流感病毒的挑战。总体而言，这项研究表明，八种 COBRA HA/NA 蛋白与鼻内佐剂的混合物是一种有前途的通用流感疫苗候选物。
流感是一种呼吸道病毒，每年在全球感染约 10 亿人，其中数百万人患有严重疾病。商业疫苗的功效因循环病毒株的不匹配而每年不同，并且可能较低。因此，每年都要相应地调整当前疫苗的配方。开发一种广谱反应性流感疫苗将减轻不同类型流感病毒给全球经济和公共卫生带来的负担。我们研究的意义在于产生一种有前途的通用疫苗候选物，可在更长的时间内提供对更广泛的病毒株的保护。
