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F plus G RSV VLP Vaccine for Improved Safety and Efficacy

F plus G RSV VLP 疫苗可提高安全性和有效性

基本信息

批准号：
10383486
负责人：
Larry J Anderson
金额：
$ 29.98万
依托单位：
RAZI PHARMA LLC
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10383486
关键词：
2 year old Adjuvant Adult Antibodies Antibody Response Antigens Attenuated Benchmarking Binding Binding Proteins Birth Bronchiolitis Cardiac Cells Cessation of life Child Clinical Data Cotton Rats Coughing Data Development Disease Dose Elderly Electron Microscopy Epithelial Cells Formalin GTP-Binding Protein alpha Subunits, Gs GTP-Binding Proteins Genes Goals Heart Histologic Hospitalization Human IgG1 Immune response Immune system Immunity Infant Infection Inflammation Inflammatory Legal patent Letters Licensure Life Lower respiratory tract structure Lung Modeling Mucous body substance Mus Pathology Peptides Persons Phase Pneumonia Pregnant Women Premature Infant Principal Investigator Proteins Pulmonary Inflammation Reporting Respiratory Syncytial Virus Infections Respiratory Syncytial Virus Vaccines Respiratory Tract Diseases Respiratory syncytial virus Respiratory syncytial virus RSV F proteins Respiratory syncytial virus RSV proteins Risk Safety Scientist Site Small Business Technology Transfer Research Spleen Structure Subunit Vaccines Sucrose Symptoms T cell response Testing Universities Vaccinated Vaccine Design Vaccines Viral Physiology Virus Virus Diseases Virus Replication Virus-like particle Western Blotting Work adaptive immune response airway epithelium aluminum sulfate base commercialization design experience immunogenic immunogenicity improved mouse model neutralizing antibody novel novel strategies novel virus older patient peptide G pre-clinical preempt prevent response success vaccine candidate vaccine development virtual

项目摘要

Project Summary Respiratory syncytial virus (RSV) is a leading cause of serious lower respiratory tract disease in infants and young children worldwide. Since infection induces only partial protection, it causes repeat infection and disease throughout life. Though a high priority for vaccine development no vaccine is yet available. The lack of success in developing a vaccine suggests novel strategies are needed to achieve success. Most of the focus for RSV subunit vaccines has been on the RSV F protein. The G protein of RSV: 1) causes inflammation that increases RSV disease and 2) provides binding to primary human airway epithelial cells to infect the cells at the primary site of infection in humans. Blocking G with antibodies prevents these effects in mice. Accordingly, inducing anti- G antibodies with a G immunogen in a vaccine, should improve both safety and efficacy. This proposal is designed to identify the optimal G protein construct to use with a pre-fusion stabilized F protein in an RSV vaccine for adults. This approach takes advantage of the pre-fusion F’s ability to induce highly levels of broadly neutralizing antibodies and the G protein’s ability to induce antibodies that both neutralize the virus and block RSV-induced host responses that cause disease. This proposal is built on the principal investigator’s (PI’s) work that 1) helped elucidate the disease caused by G, especially the central conserved domain of G (CCD-G), and 2) developed an RSV-based virus-like particle (VLP) platform for RSV vaccines. The RSV VLP platform should ~maintain the native structures of F and G to induce optimal immune responses. We propose to make and evaluate RSV VLPs with prefusion stabilized F plus different constructs of a group A, G protein or G protein peptides and a group B G protein or peptides with different adjuvants. We use the PI’s mouse model of RSV disease to determine which VLP/adjuvant is most effective at inducing F and G neutralizing antibodies, preventing virus replication and disease in RSV-challenged mice, and fails to cause enhanced disease. These studies will identify the optimal F plus G vaccine to move toward licensure. This vaccine promises to be safer and more effective than existing RSV vaccines.

项目总结