Comparative antigenicity and immunogenicity of hepadnavirus core proteins.
The hepatitis B virus core protein (HBcAg) is a uniquely immunogenic particulate antigen and as such has been used as a vaccine carrier platform. The use of other hepadnavirus core proteins as vaccine carriers has not been explored. To determine whether the rodent hepadnavirus core proteins derived from the woodchuck (WHcAg), ground squirrel (GScAg), and arctic squirrel (AScAg) viruses possess immunogen characteristics similar to those of HBcAg, comparative antigenicity and immunogenicity studies were performed. The results indicate that (i) the rodent core proteins are equal in immunogenicity to or more immunogenic than HBcAg at the B-cell and T-cell levels; (ii) major histocompatibility complex (MHC) genes influence the immune response to the rodent core proteins (however, nonresponder haplotypes were not identified); (iii) WHcAg can behave as a T-cell-independent antigen in athymic mice; (iv) the rodent core proteins are not significantly cross-reactive with the HBcAg at the antibody level (however, the nonparticulate "eAgs" do appear to be cross-reactive); (v) the rodent core proteins are only partially cross-reactive with HBcAg at the CD4+ T-cell level, depending on MHC haplotype; and (vi) the rodent core proteins are competent to function as vaccine carrier platforms for heterologous, B-cell epitopes. These results have implications for the selection of an optimal hepadnavirus core protein for vaccine design, especially in view of the "preexisting" immunity problem that is inherent in the use of HBcAg for human vaccine development.
Billaud
Jean-Noel
JN
Vaccine Research Institute of San Diego, 3030 Bunker Hill Street, Suite 300, San Diego, CA 92109, USA.
Peterson
Darrell
D
Schödel
Florian
F
Chen
Antony
A
Sallberg
Matti
M
Garduno
Fermin
F
Goldstein
Phillip
P
McDowell
Wendy
W
Hughes
Janice
J
Jones
Joyce
J
Milich
David
D
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015613:Hepadnaviridae / Q000276:immunology*; D018347:Hepadnaviridae Infections / Q000097:blood / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000097:blood* / Q000276:immunology; D007274:Injections, Intraperitoneal; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013045:Species Specificity; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology*
D018985:Epitopes, B-Lymphocyte; D006508:Hepatitis Antibodies; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines