Accession Number : ADA298648

Title :   New Approaches to Hepatitis A Vaccine Development.

Descriptive Note : Final rept. 1 Mar 89-1 Sep 94,

Corporate Author : NORTH CAROLINA UNIV AT CHAPEL HILL

Personal Author(s) : Lemon, Stanley M.

PDF Url : ADA298648

Report Date : 01 OCT 1994

Pagination or Media Count : 23

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.

Descriptors :   *MONOCLONAL ANTIBODIES, *INFECTIOUS DISEASES, *HEPATITIS, *VACCINES, PEPTIDES, DEOXYRIBONUCLEIC ACIDS, MUTATIONS, ATTENUATION, IMMUNITY, ANTIGENS, IMMUNIZATION, AMINO ACIDS, RABBITS, GLOBULINS.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE