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Novel recombinant Rotavirus vaccine utilizing the probiotic microorganism Lactobacillus acidophilus

利用益生微生物嗜酸乳杆菌的新型重组轮状病毒疫苗

基本信息

批准号：
10524015
负责人：
Zaid Abdo
金额：
$ 75.89万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-13 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10524015
关键词：
5 year old Address Adjuvant Affect Age Agonist Animals Antibiotic Resistance Antibody Response Antigens Attenuated Attenuated Vaccines Biological Assay CRISPR/Cas technology Capsid Capsid Proteins Cause of Death Cells Cessation of life Child Clinical Trials Clustered Regularly Interspaced Short Palindromic Repeats Cold Chains Country Data Developed Countries Developing Countries Development Disease Engineering Epitopes Family suidae Flagellin Genetic Transcription Genome Gnotobiotic Hospitalization Human Immune response Immunization Immunize Immunoglobulin A Inbred BALB C Mice Individual Infant Injections Intussusception Knowledge Lactobacillus acidophilus Length Licensing Licensure M cell Modeling Morbidity - disease rate Mucosal Immune Responses Mucous Membrane Mus Oral Organism Pathogenicity Peptides Populations at Risk Probiotics Proteins Recombinants Recommendation Risk Rotavirus Rotavirus Infections Rotavirus Vaccines Rotavirus disease Safety Subunit Vaccines System Technology Testing Transplantation Vaccines Viral Virulence Virus Virus Replication World Health Organization comparative efficacy diarrheal disease enteric pathogen fecal microbiome gastrointestinal immune activation immunogenic immunogenicity innovation interest microbiome microorganism mortality mouse model mucosal vaccine neutralizing antibody next generation novel novel vaccines oral vaccine porcine model programs resistance gene vaccination protocol vaccine access vaccine candidate vaccine delivery vaccine platform vaccine strategy

项目摘要

PROJECT SUMMARY / ABSTRACT Novel recombinant Rotavirus vaccine utilizing the probiotic microorganism Lactobacillus acidophilus Despite the worldwide licensure and availability of two rotavirus vaccines in 2006, it is estimated that rotavirus kills approximately 215,000 children each year. Children under the age of 5 in developing countries are significantly more likely to be affected by severe rotavirus disease as the currently available vaccines have lower efficacy (50-60%) as compared to developed nations (>85%). The ongoing morbidity and mortality as well as the risk posed by current live-attenuated vaccines, necessitate the development of a next generation human rotavirus vaccine. We have developed an orally-delivered, mucosal vaccine platform that employs Lactobacillus acidophilus. We have brought together innovative adjuvant and antigen-expression strategies in unique constructs with demonstrated potential to induce robust mucosal and systemic immune responses. This platform offers several important feasibility advantages as it employs a commensal designated as GRAS (generally regarded as safe) by the FDA, is inexpensive to produce, does not require cold-chain, and is needleless. We will utilize a novel CRISPR-Cas9 system adapted to L. acidophilus to engineer sophisticated vaccine constructs that will be tested using a homotypic mouse rotavirus challenge. Induction of homotypic and heterotypic neutralizing antibodies will be assessed using a novel, highly sensitive assay. We will assess vaccine strain colonization and potential off-target effects on the microbiome. Finally, we will perform a direct comparison of our rLA rotavirus vaccine against a human live attenuated vaccine in the gnotobiotic pig model using animals transplanted with human infant fecal microbiome. Efficacy against human rotavirus challenge will be determined. At the completion of these proposed studies, we aim to have a rLA construct ready to proceed toward human clinical trials.

项目摘要/摘要