New Approaches to Hepatitis A Vaccine Development.
Abstract
Research has been directed at the development of a safe, inexpensive and effective hepatitis A vaccine. Neutralization epitopes on the surface of the HAV capsid have been characterized in detail. A single linear antigenic site on the virus capsid which found to be reactive with a murine neutralizing monoclonal antibody. Poliovirus antigenic chimeras were engineered which expressed amino acid sequences of this HAV epitope within its VP 1 capsid protein, but were not neutralized by the cognate monoclonal antibody. Translational control elements contained within the 5' nontranslated region of the genome were mapped. Infectious HAV cDNA constructs were engineered which contain extensive deletion mutations within a pyrimidine rich region located immediately upstream of the internal ribosomal entry site. Deletion of up to 44 nts in this region did not alter the growth of the virus in BS- C-1 cells. However, extension of the deletion in a 3' direction by several additional nucleotides resulted in a marked ts 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 with inactivated vaccine, suggesting that the latter induces antibodies with relatively low affinity for the virus.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 26, 1994
- Accession Number
- ADA293328
Entities
People
- Stanley M. Lemon
Organizations
- University of North Carolina at Chapel Hill