EPIVAX, INC. — Department of Health and Human Services SBIR Phase I: NIAID

Description

DESCRIPTION provided by applicant The avian origin H N influenza virus that emerged in humans in China in presents a unique challenge to vaccine development because it is poorly immunogenic Neutralizing antibodies are not detected in acute phase infection Anti H antibody responses are significantly delayed and exhibit low avidity in comparison with antibodies generated following seasonal influenza vaccination and infection Furthermore unadjuvanted H N vaccines developed using conventional approaches elicit weak hemagglutinin inhibition HAI antibody titers in clinical trials Adjuvanted formulations may overcome this limitation but present significant regulatory challenges because adverse effects have recently been associated with adjuvanted influenza vaccines Alternative vaccine approaches are needed to redress the low immunogenicity of H N and circumvent safety risks Because HAI titers are directly related to effector CD T cell frequencies induced by vaccination we hypothesize that a vaccine strategy that enhances effector CD T cell activation will improve H N vaccine efficacy without requiring adjuvant formulation In published studies we observed that the T cell epitope content of H N virus differs significantly from more immunogenic influenza subtypes H N contains fewer T cell epitopes and some epitopes stimulate regulatory T cells Tregs that may help the virus evade effector responses needed for protection These findings suggest that H N vaccine design that carefully addresses the T cell subsets primed by immunization will overcome limitations of conventional vaccine approaches The goal of this research program is to produce an unadjuvanted influenza H N virus like particle VLP vaccine that augments effector CD T cell responses and diminishes Treg effects for enhanced protection against disease This new SBIR program will apply cutting edge computational and experimental methods that EpiVax has successfully applied against influenza and other viral and bacterial pathogens as well as deep experience in influenza VLP production and vaccine testing in collaboration with Dr Ted Ross at the University of Georgia Two different engineered VLP strategies will be tested i addition of effector epitopes and ii removal of Treg epitopes Using these prototype effector T cell epitope enhanced VLP vaccines in the proof of concept program described here we will evaluate the vaccines for immunogenicity and efficacy and move forward in a Phase II program to further optimize efficacy and complete safety toxicity studies in the run up to clinical trial PUBLIC HEALTH RELEVANCE The avian origin H N influenza virus that emerged in humans in China in presents a unique challenge to vaccine development because it is poorly immunogenic Neutralizing antibodies are not detected in acute phase infection Anti H antibody responses are significantly delayed and exhibit low avidity in comparison with antibodies generated following seasonal influenza vaccination and infection Furthermore unadjuvanted H N vaccines developed using conventional approaches elicit weak hemagglutinin inhibition HAI antibody titers in clinical trials Adjuvanted formulations may overcome this limitation but present significant regulatory challenges because adverse effects have recently been associated with adjuvanted influenza vaccines Alternative vaccine approaches are needed to redress the low immunogenicity of H N and circumvent safety risks Because HAI titers are directly related to effector CD T cell frequencies induced by vaccination we hypothesize that a vaccine strategy that enhances effector CD T cell activation will improve H N vaccine efficacy without requiring adjuvant formulation In published studies we observed that the T cell epitope content of H N virus differs significantly from more immunogenic influenza subtypes H N contains fewer T cell epitopes and some epitopes stimulate regulatory T cells Tregs that may help the virus evade effector responses needed for protection These findings suggest that H N vaccine design that carefully addresses the T cell subsets primed by immunization will overcome limitations of conventional vaccine approaches The goal of this research program is to produce an unadjuvanted influenza H N virus like particle VLP vaccine that augments effector CD T cell responses and diminishes Treg effects for enhanced protection against disease This new SBIR program will apply cutting edge computational and experimental methods that EpiVax has successfully applied against influenza and other viral and bacterial pathogens as well as deep experience in influenza VLP production and vaccine testing in collaboration with Dr Ted Ross at the University of Georgia Two different engineered VLP strategies will be tested i addition of effector epitopes and ii removal of Treg epitopes Using these prototype effector T cell epitope enhanced VLP vaccines in the proof of concept program described here we will evaluate the vaccines for immunogenicity and efficacy and move forward in a Phase II program to further optimize efficacy and complete safety toxicity studies in the run up to clinical trial