Flu Vaccine Production Using a Novel Pandemic Response and Prevention Manufacturing Method

项目摘要/摘要 目前的全球大流行突显了开发新的疫苗方法的必要性。许多 当今的方法在保护的广度和持续时间方面面临限制；对新兴市场的灵活性和适应性 菌株；制造速度和安全；以及储存和分配。SolaVAX™失活技术提供 一种使用光敏剂组合快速生产高效疫苗的优雅解决方案 (核黄素/维生素B2)和紫外线破坏病原体遗传物质，同时保留目标抗原。似然 SolaVAX衍生疫苗的优点包括：使用完整病原体更完整地呈现抗原； 多个病毒株/多个抗原变体，即多价；快速制造支点以应对紧急情况 菌株；没有有毒的灭活化学物质，可能会危及抗原构象并增加 制造复杂性；低成本、地理分布的制造；适用于病毒、细菌和 寄生病原体。在最近由BARDA和NIH支持的工作中，Raymond Goodrich博士和Izabela Ragan博士 证明了SolaVAX™-SARS-CoV2疫苗显著降低了病毒载量，减少了淋巴细胞 病毒暴露后，肺泡内有大量中性粒细胞积聚，肺泡空隙得以维持。从这些 研究表明，SolaVAX™-SARS-CoV-2研究疫苗的效力估计高达2万倍 与其他灭活方法相比，以重量/重量为基础的剂量。 该SBIR项目将侧重于评估SolaVAX方法，以创造改进的流感疫苗 由完整的灭活病毒粒子组成。尽管自2020年以来，全球的注意力一直集中在新冠肺炎上， 流感大流行的威胁仍然存在。此外，流感大流行的风险可能会因以下原因而加剧 SARS-CoV-2，考虑到全球医疗系统的负担和更多患有前病毒的个人 现有的疾病，如呼吸系统受损。目前的流感疫苗提供了不太理想的 需要保护(40%-60%)和改进多应变和/或普遍保护的方法。在……里面 有希望的初步体外研究，一种SolaVAX产生的流感疫苗提供了70%-80%的保留 血凝素(HA)活性，而福尔马林灭活后为40%-45%。该项目的第一阶段将 在这些研究的基础上建立疫苗开发过程，以产生最大限度的完全灭活 抗原完整性(AIM 1)。然后，我们将评估灭活疫苗在小鼠体内的免疫原性(AIM 2)和 对抗雪貂活体病毒攻击的有效性(AIM 3)。

PROJECT SUMMARY/ABSTRACT The current global pandemic has highlighted the need to develop new methods for creating vaccines. Many approaches today face limitations with breadth and duration of protection; flexibility and adaptability for emerging strains; manufacturing speed and safety; and storage and distribution. SolaVAX™ inactivation technology offers an elegant solution for quickly generating highly effective vaccines by using a combination of a photosensitizer (riboflavin/vitamin B2) and UV light to disrupt pathogen genetic material while preserving target antigens. Likely advantages of SolaVAX-derived vaccines include: more complete antigen presentation using whole pathogens; multiple virus strains/ multiple antigen variants, i.e. multivalent; rapid manufacturing pivot to address emergent strains; no toxic inactivating chemicals that potentially compromise antigen conformation and add to manufacturing complexity; low cost, geographically distributed manufacturing; applicable to viral, bacterial and parasitic pathogens. In recent work supported by BARDA and NIH, Drs. Raymond Goodrich and Izabela Ragan demonstrated that a SolaVAX™-SARS-CoV-2 vaccine dramatically decreased viral load, reduced lymphocytic infiltration and neutrophil accumulation, and maintained lung alveolar air space after virus exposure. From these studies, the SolaVAX™-SARS-CoV-2 investigational vaccine is estimated to be up to 20,000x more effective on a weight/weight basis of dose compared to other inactivation methods. This SBIR project will focus on the evaluation of the SolaVAX approach for creating improved influenza vaccines composed of whole inactivated virions. Although global attention has been focused on COVID-19 since 2020, the pandemic threat of influenza still exists. Moreover, the risk of a pandemic influenza may be exacerbated by SARS-CoV-2, given the burden on global healthcare systems and increased number of individuals with pre- existing conditions, such as compromised respiratory systems. Current flu vaccines provide sub-optimal protection (40-60%) and improved approaches for multi-strain and/or universal protection are needed. In promising preliminary in vitro studies, a SolaVAX-generated influenza vaccine provided 70-80% retention of hemagglutinin (HA) activity, as compared to 40-45% after inactivation by formalin. Phase I of this project will build on these studies to establish the vaccine development process that yields full inactivation with maximal antigen integrity (AIM 1). Then, we will evaluate inactivated vaccine for immunogenicity in mice (AIM 2) and efficacy against live viral challenge in ferret (AIM 3).