Nipah virus (NiV) and Hendra virus (HeV) are recently emerged BSL-4 priority pathogens which possess several biological features that make them highly adaptable for their use as bioterror agents. In 2004 two additional outbreaks of NiV have been confirmed in Bangladesh totaling some 53 human cases of infection. Several significant observations in these most recent outbreaks have been made, including a higher incidence of acute respiratory distress syndrome, possibly a higher incidence of person-to-person transmission, significantly higher case fatality rates (60-75%), and no direct link to infected livestock or domestic animals. The development of therapeutic or intervention strategies to deal with these emerging viral agents is now of importance. Our laboratory has been engaged in the structural and functional analysis of the interactions between both HeV and NiV with their host cells; performing detailed characterization of their envelope glycoproteins that are responsible for virus attachment and fusion (G and F) which are the principal antigens to which neutralizing antibody are directed against. The overall goal of this project is to characterize the immunological properties of the envelope glycoproteins of Nipah and Hendra virus; evaluating their ability to elicit a virus-neutralizing antibody responses and determining their neutralizing epitope domains. The findings derived from this short-term project will not only provide much needed information on the structural and immunological properties of their envelope glycoproteins, but will also supply critical data for future work on testing the protective efficacy of an envelope glycoprotein-based, soluble subunit vaccine for Hendra and Nipah virus in an animal model.
The specific aims of this proposal are: 1) Develop and characterize soluble forms of the F and G glycoproteins; 2) Use recombinant F and G for murine monoclonal antibody development and identify critical neutralization determinants; 3) Evaluate purified F and G as subunit vaccine immunogens. We will employ a variety of recombinant-based expression techniques and immunological assays to characterize F and G. We will evaluate monoclonal and polyclonal antibodies in both reporter-gene membrane fusion assays and in virus-neutralization assays.
