Novel delivery platform and antigen design for an effective COVID-19 vaccine

用于有效的 COVID-19 疫苗的新型递送平台和抗原设计

• 批准号: 10175713
• 负责人: SURESH K MITTAL
• 金额: $ 79.25万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-11 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10175713
• 关键词: 2019-nCoV; Adenovirus Vector; Adenoviruses; Affinity; Amino Acids; Animal Model; Antibody Response; Antibody-Dependent Enhancement; Antigens; Antiviral Agents; Autophagocytosis; B-Lymphocytes; Blood group antigen S; COVID-19; COVID-19 pandemic; COVID-19 vaccine; Cattle; Cessation of life; China; Chiroptera; Coronavirus Infections; Country; Development; Dose; Elderly; Equilibrium; Failure; Feline Coronavirus; Ferrets; Fever; Glycoproteins; Health Personnel; Human; Immune response; Immune system; Immunity; Immunization; Immunocompetence; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H7N9 Subtype; Intervention; Lung; Malaise; Mediating; Membrane; Membrane Proteins; Memory; Memory B-Lymphocyte; Mesocricetus auratus; Middle East Respiratory Syndrome Coronavirus; Morbidity - disease rate; Mucous Membrane; Mus; Myalgia; Names; Natural Immunity; Nucleoproteins; Outcome; Peptides; Pneumonia; Population; Proteins; Recombinant Vaccines; Reporting; Respiratory Failure; Risk; Role; SARS coronavirus; Secondary Immunization; Septic Shock; Severe Acute Respiratory Syndrome; Severities; Symptoms; System; T cell response; T-Lymphocyte; Time; Training; Transgenic Mice; Tuberculosis; United States; Vaccination; Vaccines; Virus; Work; adaptive immunity; base; cell mediated immune response; design; diagnostic assay; flu; genome analysis; high risk; humanized monoclonal antibodies; immunogenic; immunogenicity; influenzavirus; mortality; novel; novel coronavirus; novel vaccines; pandemic disease; pandemic influenza; pathogen; protective efficacy; relating to nervous system; vaccine delivery; vaccine development; vector; viral transmission

PROJECT SUMMARY For effective management of the COVID-19 pandemic and its second wave, the design and implementation of multiple intervention approaches are crucial. They include the development of effective antivirals, high-affinity SARS-CoV-2-neuralizing human or humanized monoclonal antibodies, rapid diagnostic assays, immunogenic and protective vaccines, strategies to mitigate virus transmissibility, and enhancing capacity related to trained medical personnel, facilities, and supplies. Due to the possibility of antibody-dependent enhancement (ADE) of COVID-19, vaccine efforts should consider the use of a novel vaccine platform and design of a relevant antigen strategy. It is essential to note that the elderly are the most vulnerable segment of the population that is at a higher risk of COVID-19 severity; the vaccine development efforts should, therefore, consider the decline in the immune competence in the elderly. We have developed a novel replication-defective (E1 & E3 deleted) bovine adenovirus (Ad) type 3 (BAd3)- based vaccine platform, which is better than the currently available Ad vector systems for providing heterologous influenza protection with dose sparing and is not impacted by the pre-existing human Ad vector immunity. Recently, we have revealed that the BAd vaccine platform provides the expression of significantly higher levels of the immunogen and innate and adaptive immunity-related factors compared to that of human Ad vectors in mice. This work suggests that the BAd vector system could serve as an excellent delivery vehicle for the development of recombinant vaccines against emerging pathogens for the elderly and other segments of the population. We have also identified a 22 amino acid residues Autophagy-Inducing Peptide (AIP) C5 (AIP-C5) from the CFP10 protein of M. tuberculosis that enhances robust T cell immune responses in mice to NP of H7N9 influenza virus when delivered through an Ad vector. It conferred complete protection against H1N1, H3N2, H5N2, H7N9, and H9N2 influenza viruses. The proposal is based on the hypothesis that immunization with the autophagy-inducing replication-deficient BAd vector expressing relevant antigen/s of SARS-CoV-2 will strengthen an effective mucosal (lung) and systemic anti-COVID-19 immunity. Under Aim 1, we will evaluate the immunogenicity and protective efficacy of a novel vaccine platform and antigen design in animal models for developing an effective COVID-19 vaccine. Whereas under Aim 2, we will investigate the vaccine-induced antibody-dependent enhancement (ADE) of SARS-CoV-2 infection, the quality of memory innate, B and T cell responses, and the durability of protective immunity in the best animal model. We believe that the use of a unique nonhuman Ad vaccine platform and novel antigen design containing AIP-C5 will yield an effective COVID-19 vaccine for all segments of the population. This effort will be of significant value to effectively flatten the COVID- 19 pandemic's trajectory and its second wave.

项目总结