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

使用新型流行病应对和预防制造方法生产流感疫苗

基本信息

批准号：
10698431
负责人：
Izabela Ragan
金额：
$ 29.89万
依托单位：
SOLARIS VACCINES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10698431
关键词：
2019-nCoV Address Air Alveolar Animal Model Animals Antibody Formation Antibody titer measurement Antigen Presentation Antigen Targeting Antigens Attention Biological Assay Blood Blood specimen COVID-19 COVID-19 vaccine Chemicals Colorado Cyclic GMP Development Disease Dose Enzyme-Linked Immunosorbent Assay Enzymes Evaluation Face Ferrets Formalin Formulation General Population Genetic Materials Geography Growth Healthcare Systems Hemagglutinin Histopathology Immunization In Vitro Inactivated Vaccines Individual Infection Influenza Influenza A Virus, H1N1 Subtype Influenza A Virus, H3N2 Subtype Influenza A virus Influenza B Virus Intramuscular Kinetics Lectin Link Lung Lymphocytic Infiltrate Methods Modeling Molecular Conformation Mus Nasal turbinate bone structure Neuraminidase Neutralization Tests Nose Nucleoproteins Phase Photosensitizing Agents Plaque Assay Poison Process Production Protein Analysis Proteins Resources Respiratory System Riboflavin Risk Safety Sampling Small Business Innovation Research Grant Speed System Technology Testing Tissues Trachea Trademark Ultraviolet Rays United States National Institutes of Health Universities Vaccinated Vaccine Production Vaccines Variant Vascular blood supply Viral Viral Antigens Viral Load result Viral Proteins Virion Virus Weight Work antibody test cost efficacy evaluation efficacy study flexibility global health improved in vivo influenza virus vaccine influenzavirus manufacture manufacturing process development neutrophil new pandemic novel vaccines pandemic disease pandemic influenza pandemic potential pandemic response pathogen preservation prevent pandemics respiratory technology platform vaccine candidate vaccine development vaccine evaluation vaccine immunogenicity

项目摘要

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).

项目概要/摘要当前的全球大流行凸显了开发制造疫苗的新方法的必要性。当今的方法面临保护广度和持续时间的限制；菌株；生产速度和安全性；以及 SolaVAX™ 灭活技术。通过使用光敏剂组合快速生成高效疫苗的优雅解决方案（核黄素/维生素 B2）和紫外线可能会破坏病原体遗传物质，同时保留目标抗原。 SolaVAX 衍生疫苗的优点包括：使用完整病原体进行更完整的抗原呈递；多种病毒株/多种抗原变体，即多价快速制造，以应对紧急情况；菌株；没有有毒的灭活化学物质，可能会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、细菌和在 BARDA 和 NIH 的支持下，Raymond Goodrich 和 Izabela Ragan 博士最近的工作。证明 SolaVAX™-SARS-CoV-2 疫苗可显着降低病毒载量，减少淋巴细胞浸润和中性粒细胞积聚，并在病毒暴露后维持肺泡空气空间。研究表明，SolaVAX™-SARS-CoV-2 研究疫苗的有效性估计提高了 20,000 倍与其他灭活方法相比，剂量的重量/重量基础。该 SBIR 项目将重点评估用于改进流感疫苗的 SolaVAX 方法尽管自 2020 年以来全球注意力一直集中在 COVID-19 上，流感大流行的威胁依然存在，而且流感大流行的风险可能会加剧。考虑到全球医疗保健系统的负担以及患有新冠肺炎的人数增加，SARS-CoV-2 现有的条件，例如受损的呼吸系统，目前的流感疫苗效果不佳。需要保护（40-60%）和改进的多菌株和/或通用保护方法。初步体外研究显示，SolaVAX 生成的流感疫苗具有 70-80% 的保留率与福尔马林灭活后的 40-45% 相比，该项目的血凝素 (HA) 活性将下降。以这些研究为基础，建立疫苗开发过程，以最大程度地实现完全灭活然后，我们将评估灭活疫苗在小鼠中的免疫原性（AIM 2）和对雪貂活病毒攻击的功效（AIM 3）。