Development of an improved intranasal vaccine against influenza

开发改进的鼻内流感疫苗

• 批准号: 10546098
• 负责人: Ian James Amanna
• 金额: $ 27.51万
• 依托单位: NAJIT TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546098
• 关键词: Adjuvant; Adult; Antibody Response; Antigen Presentation; Antigens; Attenuated; Bell Palsy; Cells; Cessation of life; Child; Clinical; Coupled; Data; Detergents; Development; Disease; Ebola; Elderly; Epitopes; FluMist; Formaldehyde; Formalin; Formulation; Generations; Hemagglutinin; Hydrogen Peroxide; Immune response; Immunity; Immunization; Immunization Programs; Inactivated Vaccines; Infant; Influenza; Influenza vaccination; Intranasal Administration; Ionic Strengths; Kinetics; Legal patent; Link; M cell; Mediating; Methods; Modeling; Morbidity - disease rate; Mucous Membrane; Mus; Needles; Nose; Oxidation-Reduction; Performance; Peroxides; Persons; Process; Public Health; Recombinants; Recording of previous events; Route; Seasons; Site; Structure; Subunit Vaccines; Surface; Technology; Testing; Transition Elements; Vaccination; Vaccine Antigen; Vaccine Research; Vaccines; Viral Antigens; Virus; Virus Replication; Vulnerable Populations; World Health Organization; aged; base; combat; flu; immunogenic; immunogenicity; improved; influenza virus vaccine; innovation; mortality; mucosal site; nanoparticle; next generation; nonhuman primate; novel; novel strategies; novel vaccines; oxidation; parenteral administration; pathogenic bacteria; pathogenic virus; preservation; prevent; protective efficacy; seasonal influenza; side effect; subcutaneous; uptake; vaccine development; vaccine efficacy; vaccine formulation; vaccine platform

Despite the development of several types of influenza vaccines (live-attenuated, inactivated, subunit), the World Health Organization estimates that seasonal influenza is still responsible for 3-5 million cases of severe disease and 290,000-650,000 deaths each year. Although vaccination programs have helped to reduce the morbidity and mortality associated with seasonal influenza, current vaccine approaches are limited by poor vaccine- mediated immunity and low vaccination coverage. To overcome suboptimal immune responses to influenza vaccination, we have developed an advanced hydrogen peroxide-based, site-directed oxidation technology that renders viruses fully inactivated while preserving protective structures/epitopes on the virus surface including fully maintained HA (hemagglutinin) activity. Our preliminary data shows that immunization of mice with our 1st- generation peroxide-inactivated vaccine by either the subcutaneous, transcutaneous, or intranasal routes of administration leads to full protection against lethal influenza challenge. In these proposed studies, we describe our 2nd-generation HydroVax platform technology and the approaches that we will take to further optimize vaccine potency following intranasal vaccination. By improving the structural integrity of the vaccine antigen, coupled with the ease and acceptability of an intranasal route of administration, we hope to improve both vaccine potency and vaccination coverage that together, will greatly reduce the impact of seasonal influenza among vulnerable populations including infants and the elderly.

尽管开发了几种类型的流感疫苗（减毒活疫苗、灭活疫苗、亚单位疫苗）， 卫生组织估计，季节性流感仍造成300万至500万例严重疾病 每年有29万到65万人死亡。虽然疫苗接种计划有助于降低发病率， 以及与季节性流感相关的死亡率，目前的疫苗方法受到疫苗质量差的限制- 介导的免疫力和疫苗接种覆盖率低。为了克服对流感的次优免疫反应， 疫苗接种，我们已经开发出一种先进的过氧化氢为基础的，定点氧化技术， 使病毒完全失活，同时保留病毒表面上的保护性结构/表位， 完全保持HA（血凝素）活性。我们的初步数据显示，用我们的第一代- 通过皮下、经皮或鼻内途径， 施用导致针对致命流感攻击的完全保护。在这些研究中，我们描述了 我们的第二代HydroVax平台技术以及我们将采取的进一步优化疫苗的方法 鼻内接种后的效力。通过改善疫苗抗原的结构完整性， 由于鼻内给药途径的容易性和可接受性，我们希望提高疫苗的效力， 和疫苗接种覆盖率，将大大减少季节性流感对脆弱人群的影响。 包括婴儿和老年人在内的人群。