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

Description

DESCRIPTION provided by applicant Influenza is associated with deaths in the US each year and vaccination is the best strategy for the prevention of influenza A major obstacle to the development of widely effective influenza vaccines is the considerable antigenic variation across strains and types of influenza viruses Influenza A H N and H N and influenza B viruses have co circulated each season since and an updated trivalent vaccine has been required every year to protect against the most recent circulating strains For Influenza B it is particularly challenging to select a single strain for the licensed trivalent vaccine Every season two antigenically distinct lineages of B strains Yamagata and Victoria lineages co circulate worldwide thus there is often inadequate protection from the vaccine against influenza B To address this issue a quadrivalent vaccine comprised of one H N one H N and two B antigens will be offered for the influenza season The additional component should reduce the morbidity and mortality associated with influenza B infections However a quadrivalent vaccine will not solve many of the problems that persist with influenza vaccines such as i lack of vaccine efficacy due to mismatched vaccine strains particularly for more deadly H N and H N ii no protection against pandemic viruses and iii a continued requirement for annual update of the vaccine Developing more andquot universalandquot vaccines or even for the individual components of the vaccine is essential for improving vaccine efficacy as well as pandemic preparedness We have used a directed molecular evolution approach to identify novel variants of the influenza B hemagglutinin or HA B that elicit cross lineage activity to both Yamagata and Victoria viruses Here we propose to evaluate the feasibility of developing these lead HA B immunogens as a universal influenza B vaccine by analysis of the breadth of the protective response and serum neutralizing activity elicited by the lead variants We will produce the HA B variants as virus like particle vaccines and use them to immunize ferrets which are a widely used highly relevant animal model for the study of influenza Ferrets will be challenged with both lineages of influenza B to deter mine if the HA B variant vaccines provide improved cross lineage protection In addition we will extensively characterize the sera from immunized ferrets against a large panel of B viruses to assess the degree of inter and intra lineage neutralization breadth Finally we will carry out assays to learn if conserved epitopes in HA such as epitopes near the receptor binding site or in the stem domain are targeted by these vaccines A single widely protective B component would be a significant and innovative advance for influenza vaccines It would relieve constraints placed on manufacturing capacity and timelines as it could be produced year round Such a vaccine could eliminate the need for yearly vaccination against influenza B Importantly a universal B component would free up space in a quadrivalent vaccine for other more deadly components particularly where pre existing immunity is lacking H N H N H N etc Inclusion of these viruses in the seasonal vaccine could save lives in the face of a pandemic PUBLIC HEALTH RELEVANCE The annual influenza season is responsible for considerable sickness and death especially among the more vulnerable members of the population such as children and the elderly Since flu strains change from year to year a vaccine that protects against many strains and avoids the need for annual immunization would be of great value This research Proposal will investigate a novel way to protect against different strains of influenza virus and could serve as the basis for improved vaccines