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RNA Vaccine Innovations for TB: Targeting the Mucosa

结核病 RNA 疫苗创新：针对粘膜

基本信息

批准号：
10442288
负责人：
STEVEN GREGORY REED
金额：
$ 55.07万
依托单位：
HDT BIO CORPORATION
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：
2022-04-22 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10442288
关键词：
Address Adjuvant Aerosols Agonist Alphavirus Animals Antigens Area Brazil Businesses COVID-19 vaccine Cellular Immunity Clinical Clinical Trials Collaborations Combined Vaccines Communicable Diseases Complement Cost of Illness Coupled Development Dose Formulation Generations Goals Human Immune response Immunity Immunization India Instruction Intellectual Property Intramuscular Kinetics Lipids Lung Manufactured Supplies Measures Mind Mucosal Immune Responses Mucosal Immunity Mucous Membrane Mus Mycobacterium tuberculosis Mycobacterium tuberculosis antigens Natural Products Pathway interactions Phase Phase I Clinical Trials Phase II Clinical Trials Process Production Protein Subunits Proteins RNA RNA vaccination RNA vaccine Recombinant Proteins Regimen Replicon Risk Route Safety Signal Transduction Subunit Vaccines System T-Lymphocyte TLR3 gene TLR4 gene Technology Testing Tuberculosis Tuberculosis Vaccines Vaccines adaptive immune response base clinical development clinically relevant cost effective design disorder prevention immunogenicity improved in vivo innovation large scale production nanoparticle nonhuman primate novel prevent response success vaccination strategy vaccine candidate vaccine delivery vaccine development vaccine discovery vaccine distribution vaccine platform

项目摘要

PROJECT SUMMARY/ABSTRACT Our team - in collaboration with other vaccine developers - has been actively involved in tuberculosis (TB) vaccine discovery for the past three decades and led the team that developed the M72 vaccine that has provided proof of concept for effective subunit TB vaccines. Obstacles limiting commercial deployment of M72 include limited efficacy (~50% prevention of disease) and cost of goods for large-scale production. With these considerations in mind, our group developed a second-generation subunit vaccine, ID93, which consists of four protein antigens (M72 has two) formulated with a synthetic TLR4 targeted adjuvant formulation, as opposed to the natural product-based adjuvant contained in the M72 vaccine. ID93 has progressed to Phase 2 human clinical trials, with promising results and is currently in further development. Human immune responses measured against the ID93 components have been instructive and have allowed further antigen prioritization with a goal of complementing the antigens of M72. We have concurrently developed a new RNA vaccine platform - now in clinical development as a COVID-19 vaccine which may be approved in India in summer 2021 - and that induced potent cellular immunity and can be scaled in a cost-effective manner. Using a select panel of antigens, we will apply our RNA technology for inducing effective systemic and mucosal immune responses in mice and non-human primates. In addition, each of our RNA based adjuvants, TLR3 and RIG-I agonists, both being effective inducers of both innate and adaptive immune responses adds an innovative aspect. In this proposal, our innovation comes from three main areas of emphasis: First is optimization of the RNA vaccine technology by using new replicons and delivery systems. Second is applying RNA vaccination with subunit protein/adjuvant boosting, using adjuvants of known efficacy (TLR4 agonists) in comparison with novel adjuvants that signal through the TLR-3 or RIG-I pathways. Neither of these have been exploited extensively for infectious disease vaccines - particularly in the area of mucosal immunity. The third area comes from innovation in manufacturing and supply: We have novel processes for the production of TBRNA that were transferred to India (Gennova) and Brazil (CIMATEC). Gennova has already produced 1 million doses, with a target of 100 million by year-end, and has completed Phase 1 and 2 clinical trials in India. Similarly, we have acquired large- scale access to our adjuvant molecules (TLR4, TLR3, RIG-I), all synthetic, thus avoiding the intellectual property roadblock encountered with M72.

项目总结/文摘