New Approaches to Hepatitis A Vaccine Development.

Hepatitis A virus HAV has historically been an important cause of morbidity among U.S. soldiers in the field. Work under this contract is directed at the development of a safe, inexpensive and effective hepatitis A vaccine for use in military personnel. Two main research approaches are under investigation. First, we are characterizing neutralization escape mutants of HAV and examining synthetic oligopeptides representing the suspected surface structures of HAV. Octapeptides have been synthesized on polyethylene pins and probed with polyclonal and monoclonal antibodies in an effort to identify antigenic and potentially immunogenic sequences. We have also determined the ability of poliovirus-HAV chimeric viruses to elicit neutralizing antibodies to HAV. The second approach involves the construction of an -infectious cDNA construct derived from a virulent but cell culture-adapted variant of HAV. Genetic manipulation of such a construct will allow alternative approaches to the development of attenuated vaccine candidates. A third aim is to utilize PCR- related technology for identification of specific strains of HAV. Hepatitis A vaccine Synthetic oligopeptides Monoclonal antibodies RAD 1.