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Safety and immunogenicity of a novel Rift Valley fever candidate vaccine, RVax-1

新型裂谷热候选疫苗 RVax-1 的安全性和免疫原性

基本信息

批准号：
10353404
负责人：
Tetsuro Ikegami
金额：
$ 38.61万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-10 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10353404
关键词：
Abortion Rates Affect Africa South of the Sahara Animal Experiments Animal Model Animals Area Attenuated Attenuated Vaccines Blindness Callithrix Callithrix jacchus jacchus Category A pathogen Cattle Cells Characteristics Clinical Containment Country Culicidae Disease Disease Outbreaks Dose Egypt Encephalitis Ensure Enzymes Fetus Generations Genes Genetic Markers Goals Goat Health Hemorrhage Human Immunity Infant Intramuscular Investigational Drugs Knowledge Liver Madagascar Medical Midgut Military Personnel Modeling Mus National Institute of Allergy and Infectious Disease Neonatal Mortality Open Reading Frames Phase I/II Trial Phenotype Placenta Play Predisposition Pregnancy Pregnant sheep Production Public Health Quantitative Evaluations Rattus Recombinants Rift Valley Fever Rift Valley fever virus Role Route Ruminants Safety Saudi Arabia Silent Mutation Sprague-Dawley Rats Syndrome Testing Texas Tissues United States National Institutes of Health Universities Vaccinated Vaccination Vaccines Vero Cells Vertical Disease Transmission Viral Viremia Virus Virus Diseases World Health Organization Yemen Zoonoses attenuation experimental study fetal immunogenic immunogenicity malformation mosquito-borne mouse model mutant neutralizing antibody novel pre-clinical preclinical evaluation pregnant professional atmosphere protective efficacy prototype research clinical testing reverse genetics vaccine candidate vector mosquito

项目摘要

Specific Aims Rift Valley fever (RVF), a mosquito-borne zoonotic viral disease affecting ruminants and humans endemic to sub-Saharan Africa, Egypt, Saudi Arabia and Yemen, is classified as Category A Priority Pathogen by the NIH/NIAID and the Blueprint priority disease by the World Health Organization. With One Health approach, a control of infected animals and mosquitoes are important to eradicate RVF from specific areas, whereas vaccinated humans will support overall activities including the handling of infected animals. There are, however, no licensed RVF vaccines for human use. Live-attenuated MP-12 vaccine, which was conditionally licensed in 2013 as a veterinary RVF vaccine in the U.S., had Investigational New Drug (IND) vaccine status, it has now been replaced with weakly immunogenic inactivated RVF candidate vaccine under IND. To develop a highly immunogenic and safe RVF candidate vaccine for human use, we have generated a novel live-attenuated candidate vaccine for RVF, termed “RVax-1”, which encodes more than 500 silent mutations throughout the open reading frame and a truncation of 78kD/NSm genes. Our central hypothesis is that the RVax-1 candidate vaccine is highly immunogenic in mice and marmosets via the intramuscular route with a single dose, highly attenuated in pregnant rat placenta and in infant mice, and disseminate poorly in mosquito vectors. The overall objective is characterize the immunogenicity, safety, and efficacy of the RVax-1 candidate vaccine in mice, rats, and marmosets, and to determine the level of viral dissemination in mosquitoes, in order to fill the gaps in knowledge regarding this candidate vaccine and move forward into IND-enabling preclinical and, subsequently, clinical evaluation. The work environment is ideal because the high containment facilities at the University of Texas Medical Branch are suitable for animal experiments, and SUNY Upstate Medical University supports mosquito experiments. The long-term goal of our study is to move the RVax-1 vaccine forward into preclinical evaluation, production under Good Manufacturing Practice, and Phase 1/2 trials. Specific Aim 1: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a mouse model. Specific Aim 2: To characterize the mosquito dissemination of RVax-1. Specific Aim 3: To characterize the attenuation, immunogenicity, and protective efficacy of RVax-1 in a marmoset model. Specific Aim 4: To characterize the attenuation of RVax-1 in rat placenta. Successful completion of proposed project will qualify RVax-1 for further characterization in preclinical and clinical evaluation.

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