RBD recombinant protein-based SARS vaccine for biodefense

用于生物防御的 RBD 重组蛋白 SARS 疫苗

• 批准号: 8465826
• 负责人: Maria Elena Bottazzi
• 金额: $ 108.53万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-04 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8465826
• 关键词: Adjuvant; Animals; Antibody Formation; Antigen Receptors; Bacteria; Binding; Biochemical; Biological Assay; Blood; Buffers; Categories; Clinical; Clinical Trials; Communicable Diseases; Contractor; Coronavirus; Cyclic GMP; Data; Development; Development Plans; Disease Outbreaks; Disease Outcome; Drug Formulations; Economics; Emergency Situation; Emerging Communicable Diseases; Epitopes; Evaluation; Excipients; Fermentation; Future; Home environment; Human; Immune; Immune response; Immunization; Infection; Institutes; International; Laboratories; Lead; Link; Lipid A; Maryland; Medical; Medicine; Mus; National Institute of Allergy and Infectious Disease; New York; Nonprofit Organizations; Oral Poliovirus Vaccine; Preparation; Prevention; Procedures; Process; Production; Protein S; Proteins; Public Health; Readiness; Recombinant Proteins; Recombinant Vaccines; Recombinants; Regimen; Regulatory Affairs; Reproducibility; Research; Research Institute; Risk; Scientist; Severe Acute Respiratory Syndrome; Solid; Structure; System; TLR4 gene; Techniques; Technology; Technology Transfer; Testing; Texas; TimeLine; Toxicology; Transgenic Mice; Transgenic Model; Translating; Tropical Disease; Universities; Vaccine Antigen; Vaccines; Virus; Yeasts; aluminum sulfate; base; biodefense; cell bank; clinical lot; college; frontier; human disease; immunogenicity; in vivo; innovation; meetings; mouse model; neglect; neutralizing antibody; novel; pandemic disease; pathogen; pre-clinical; prevent; product development; quality assurance; receptor binding; research clinical testing; response; social; tool; vaccine candidate; vaccine efficacy

DESCRIPTION (provided by applicant): The 2002-2003 pandemic of severe acute respiratory syndrome (SARS) posed an enormous threat to global public health and the social and economic stability. Its causative pathogen, the SARS-associated coronavirus (SARS-CoV), has been classified by NIAID as a Category C Priority Pathogen. SARS outbreaks remain a serious concern mainly due to possible zoonotic reintroduction of SARS-CoV into humans, accidental release from a laboratory or deliberate spreading of the virus by a bioterrorist attack. Therefore, an effective and safe vaccine is urgently needed for preventing future SARS outbreaks and for biodefense preparedness. We have identified a highly promising lead candidate vaccine antigen, the receptor binding domain (RBD) of the SARS- CoV spike (S) protein that contains the major neutralizing epitopes and can induce potent neutralizing antibody response and protection in animals against SARS-CoV infection. To rapidly translate our initial proof of concept findings into a solid platform of clinical trials, a consortium of experts was put together consisting of scientists from Baylor College Medicine, the new home of Sabin Vaccine Institute's product development partnership (BCM-Sabin), the New York Blood Center (NYBC) and the University of Texas Medical Branch (UTMB), and in partnership with industrial partners and non-profit organizations. The specific aims of this application are: (1) Expression, purification and pre-clinical characterization of the recombinant RBD (rRBD) protein as a vaccine candidate. The rRBD protein will be expressed in bacteria and yeast expression systems and one of these expression systems will be selected for subsequent studies based on yields, purity, stability, antigenicity, functionality, immunogenicity, and efficacy of the rRBD protein. The immunization regimens will be optimized and the ability of rRBD protein to induce cross-neutralizing antibody response, cross-protection and long-term immune responses and protection will be assessed. (2) Process development, characterization, formulation and stability profiling. A scalable and reproducible fermentation process for rRBD (10 liter scale) and a purification process using chromatographic technologies will be developed. Reproducibility will be confirmed. The specific product quality assays and vaccine formulations with alum and/or glucopyrranosyl lipid A (GLA), an innate adjuvant, will be developed. These assays and procedures will serve the basis for formal lot release and stability evaluation post-manufacturing. (3) Technology transfer, cGMP Manufacture, GLP toxicology and IND Preparation. The cell bank production, production processes and the formulation technology for the rRBD-based SARS vaccine will be transferred to Walter Reed Army Institute of Research (WRAIR) pilot facility for 60-L scale GMP manufacture, formulation and fill and finish. The clinical lots will be released by Sabin- Texas and following a pre-IND meeting with the U.S. FDA, GLP toxicology will be initiated at Frontier Biosciences, a Maryland-based contractor.

描述（由申请人提供）：2002-2003年严重急性呼吸系统综合症（SARS）大流行对全球公共卫生和社会经济稳定构成巨大威胁。其致病病原体sars相关冠状病毒（SARS-CoV）已被NIAID列为C类优先病原体。SARS疫情仍然是一个严重问题，主要原因是可能将SARS冠状病毒重新引入人类，从实验室意外释放或通过生物恐怖袭击故意传播病毒。因此,