New Approaches to Hepatitis A Vaccine Development.
Abstract
Neutralization epitopes on the surface of the hepatitis A virus (HAV) capsid were characterized in detail. A single antigenic site on the virus capsid was found to be reactive with one murine neutralizing monoclonal antibody, but larger peptides representing this region did not elicit anti-HAV neutralizing antibodies in rabbits. Poliovirus antigenic chimeras were engineered which expressed amino acid sequences of HAV epitopes, but these chimeras lacked relevant HAV antigenicity and immunogenicity. The structure and function of the 5 nontranslated region of the genome was characterized. Translational control elements were mapped. Infectious HAV cDNA constructs were engineered which contain large deletion mutations within a pyrimidine rich region located immediately upstream of the internal ribosomal entry site. Some of these mutations result in a marked temperature-sensitive phenotype. The attenuating effect of these mutations remains under study. Significant qualitative differences were demonstrated in anti-HAV antibodies present following administration of immune globulin vs. active immunization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1994
- Accession Number
- ADA298648
Entities
People
- Stanley M. Lemon
Organizations
- University of North Carolina at Chapel Hill