DNA Prime / Subunit Boost Multi-Antigen Universal Influenza Vaccine

ABSTRACT A universal influenza vaccine is believed to be possible if conserved regions of influenza are effectively targeted and appropriate immune responses are generated against those targets The enhanced safety stability and accelerated product development generally provided by DNA vaccination make it an appealing approach to develop such a universal influenza vaccine Unfortunately immune responses to universal influenza antigens are typically weak and in the past DNA vaccination of humans has been disappointing To overcome these and other obstacles to developing an effective practical and truly universal influenza vaccine we intend to deliver our vaccine using a DNA prime protein boost regimen and employ novel immunogens derived from the following three conserved influenza A antigens the stem region of hemagglutinin HA the matrix protein ectodomain M e and the nucleoprotein NP We believe that together these antigens will evoke the immunological breadth necessary to protect against a broad range of both seasonal and potential pandemic influenza strains We will also use a potent DNA adjuvant combination to maximize immunogenicity and to tune the responses toward a Th phenotype Finally we will utilize a recombinant protein boost to amplify the humoral immune responses and increase their durability In this Phase I SBIR we will construct and express our influenza A immunogens and verify their immunogenicity and protective efficacy in mice to determine if the vaccine provides a wide breadth of protection from divergent seasonal and pandemic influenza A strains If we are successful in this Phase I proof of concept study we will move on to test our vaccine in a macaque challenge model under a Phase II application and begin development on influenza B and possibly type C immunogens PROJECT NARRATIVE The objective of this project is to develop a DNA prime subunit boost universal influenza vaccine Such a vaccine is needed to combat seasonal and pandemic influenza outbreaks and to lessen the dependency on seasonal vaccines