Advantages to the use of rodent hepadnavirus core proteins as vaccine platforms.
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.
Billaud
Jean-Noel
JN
Vaccine Research Institute of San Diego, CA 92109, United States.
Peterson
Darrell
D
Lee
Byung O
BO
Maruyama
Toshiyuki
T
Chen
Antony
A
Sallberg
Matti
M
Garduño
Fermin
F
Goldstein
Phillip
P
Hughes
Janice
J
Jones
Joyce
J
Milich
David
D
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
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