title: Advantages to the use of rodent hepadnavirus core proteins as vaccine platforms.
abstract: The hepatitis B core antigen (HBcAg) has been proposed as a useful particulate carrier platform for poorly immunogenic peptidic and carbohydrate B cell epitopes. However, biochemical and immunologic impediments have plagued this technology. Specifically, the "assembly" problem characterized by the low yield of unstable hybrid particles resulting from the insertion of foreign sequences and the "pre-existing immunity" problem due to the fact that the HBcAg is derived from a human pathogen have limited the development of this carrier technology. As a means of addressing the "pre-existing immunity" problem we have used the core proteins from the rodent hepdnaviruses. A number of advantages to the use of the rodent hepadnaviral core proteins as opposed to the HBcAg for vaccine design were defined including: equal or superior immunogenicity at the T and B cell levels; the use of the rodent core proteins does not compromise the anti-HBc diagnostic assay; the efficacy of the rodent core proteins as vaccine carriers will not be limited by pre-existing anti-HBc antibodies that are present in previously and currently HBV-infected persons; and the HBcAg-specific tolerance present in HBV chronic carriers can be circumvented by the use of the rodent core proteins.
authors.affiliation: Vaccine Research Institute of San Diego, CA 92109, United States.
authors.forename: Jean-Noel
authors.initials: JN
authors.lastname: Billaud
authors.forename: Darrell
authors.initials: D
authors.lastname: Peterson
authors.forename: Byung O
authors.initials: BO
authors.lastname: Lee
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Antony
authors.initials: A
authors.lastname: Chen
authors.forename: Matti
authors.initials: M
authors.lastname: Sallberg
authors.forename: Fermin
authors.initials: F
authors.lastname: Garduño
authors.forename: Phillip
authors.initials: P
authors.lastname: Goldstein
authors.forename: Janice
authors.initials: J
authors.lastname: Hughes
authors.forename: Joyce
authors.initials: J
authors.lastname: Jones
authors.forename: David
authors.initials: D
authors.lastname: Milich
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D018984:Epitopes, T-Lymphocyte; D005822:Genetic Vectors; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017919:Hepatitis B Virus, Woodchuck / Q000378:metabolism*; D006513:Hepatitis B e Antigens / Q000235:genetics; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D018984:Epitopes, T-Lymphocyte; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan