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

项目总结/摘要 目前的全球大流行突出了开发新方法制造疫苗的必要性。许多 目前的做法在保护的广度和期限方面面临局限性;对新兴市场的灵活性和适应性 菌株;生产速度和安全性;以及储存和分配。SolaVAX™灭活技术提供 一种通过使用光敏剂的组合快速产生高效疫苗的优雅解决方案， （核黄素/维生素B2）和UV光来破坏病原体遗传物质，同时保留靶抗原。可能 SolaVAX衍生疫苗的优点包括：使用完整病原体的更完整的抗原呈递; 多种病毒株/多种抗原变体，即多价;快速生产以解决突发事件 菌株;不含可能损害抗原构象并增加 制造复杂性;低成本，地理分布制造;适用于病毒，细菌和 寄生病原体在最近由巴尔达和国家卫生研究院支持的工作中，雷蒙德古德里奇和伊莎贝拉拉根博士 研究表明，SolaVAX™-SARS-CoV-2疫苗显著降低了病毒载量，减少了淋巴细胞 浸润和中性粒细胞积聚，并维持病毒暴露后的肺泡气隙。从这些 根据研究，SolaVAX™-SARS-CoV-2研究疫苗对以下疾病的有效性估计高出20，000倍： 与其他灭活方法相比，剂量的重量/重量基础。 该SBIR项目将重点评估SolaVAX方法用于创建改进的流感疫苗 由完整的灭活病毒体组成。尽管自2020年以来，全球关注的焦点一直集中在COVID-19上， 流感大流行的威胁仍然存在。此外，大流行性流感的风险可能会因以下因素而加剧： SARS-CoV-2，考虑到全球医疗保健系统的负担和越来越多的人患有前 现有的条件，如受损的呼吸系统。目前的流感疫苗提供了次优的 保护（40-60%）和用于多菌株和/或通用保护的改进方法是需要的。在 有希望的初步体外研究，SolaVAX产生的流感疫苗提供了70-80%的保留， 血凝素（HA）活性，相比之下，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， 抗原完整性（AIM 1）。然后，我们将评估灭活疫苗在小鼠中的免疫原性（AIM 2）， 在雪貂中对抗活病毒攻击的效力（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).