?Influenza A is an enveloped negative single-stranded RNA virus that infects a wide range of avian and mammalian species. Human infection mainly involves the upper and lower respiratory epithelial tracts, with approximately 20% of children and 5% of adults worldwide experiencing symptomatic influenza each year. During an average epidemic season in the United States, an influenza season of typical severity results in >100,000 cases requiring hospitalization and >30,000 deaths, with 90% of the morbidity and mortality occurring in the elderly (?65 years of age). Use of a conventional vaccine strategy for control of influenza A may lead to primary vaccine failure because of vulnerability to antigenic drift and emergence of unmatched epidemic strains. A vaccine strategy employing an influenza antigen which is less susceptible to antigenic variation would be a major improvement. The overall purpose of this proposal is the development and testing of a novel HA stem trimer antigen produced with the SutroVax cell free expression technology. The antigen has been produced in our laboratory using a commercially viable process at yields (~1 g/L) which indicate this could be developed into a prophylactic vaccine product. The specific goals of this proposal are to 1) produce and purify a non-his tagged version of the HA stem; 2) determine immunogenicity and protection in mice using representative H1 and H3 strains. Accomplishment of these goals will setup a Phase II SBIR which will focus on the scale-up and testing of the candidate vaccine in ferrets and non-human primates prior to Phase I human clinical trials.
Public Health Relevance Statement: Public Health Relevance: Use of a conventional vaccine strategy for control of influenza A may lead to primary vaccine failure because of vulnerability to antigenic drift and emergence of unmatched epidemic strains. Accomplishment of the goals of this proposal will evaluate an HA stem trimer influenza vaccine which provides greater protection and be less susceptible to unmatched influenza strains.
Project Terms: Adjuvant; Adult; Age-Years; Antigenic Variation; Antigens; base; Binding; Birds; California; Cell membrane; Cells; Cessation of life; Child; Clinical Trials; clinically relevant; Communicable Diseases; Complex; Development; Dose; Elderly; Epidemic; Epithelial; Epitopes; Escherichia coli; Excipients; experience; Failure; Family suidae; Ferrets; Generations; Goals; Hemagglutinin; Hong Kong; Hospitalization; Human; Immune response; Immunization; immunogenic; immunogenicity; Immunologist; in vivo; Individual; Infection; Influenza; Influenza A virus; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N1 Subtype; influenza epidemic; Influenza virus vaccine; Laboratories; Lead; Legal patent; Licensing; Measures; Methods; Modeling; Molecular Conformation; Monoclonal Antibodies; Morbidity - disease rate; mortality; mouse model; Mus; mutant; neutralizing antibody; nonhuman primate; novel; pandemic disease; Phase; phase 1 study; polyhistidine; preclinical evaluation; Preparation; Prevention; Process; product development; Production; programs; prophylactic; Protein Biosynthesis; protein expression; Proteins; public health relevance; respiratory; response; Rights; RNA Viruses; scale up; Schedule; Scientist; Seasons; Severities; Small Business Innovation Research Grant; Solid; stem; success; Technology; Tertiary Protein Structure; Testing; Toxicology; Training; United States; Universities; Vaccinated; Vaccination; Vaccine Adjuvant; vaccine candidate; vaccine development; vaccine evaluation; Vaccine Research; Vaccines; Variant; Viral; Virus; Virus Diseases; Work
