Characterization of humoral and CD4+ cellular responses after genetic immunization with retroviral vectors expressing different forms of the hepatitis B virus core and e antigens.
The humoral and CD4+ cellular immune responses in mice following genetic immunization with three retroviral vectors encoding different forms of hepatitis B virus core antigen (HBcAg) and e antigen (HBeAg) were analyzed. The retroviral vectors induced expression of intracellular HBcAg (HBc[3A4]), secreted HBeAg (HBe[5A2]), or an intracellular HBcAg-neomycin phosphoryltransferase fusion protein (HBc-NEO[6A3]). Specific antibody levels and immunoglobulin G isotype restriction were highly dependent on both the host major histocompatibility complex and the transferred gene. Humoral and CD4+ cellular HBcAg and/or HBeAg (HBc/eAg)-specific immune responses following retroviral vector immunization were of a lower magnitude but followed the same characteristics compared with those after immunization with HBc/eAg in adjuvant. Two factors influenced the humoral responses. First, in vivo depletion of CD8+ cells in HBc-NEO[6A3]-immunized H-2k mice abrogated both HBcAg-specific antibodies and in vitro-detectable cytotoxic T lymphocytes. Second, priming of H-2b mice with an HBc/eAg-derived T-helper (Th) peptide in adjuvant prior to retroviral vector immunization greatly enhanced the HBc/eAg-specific humoral responses to all three vectors, suggesting that insufficient HBc/eAg-specific CD4+ Th-cell priming limits the humoral responses. In conclusion, direct injection of retroviral vectors seems to be effective in priming HBc/eAg-specific CD8+ but comparatively inefficient in priming CD4+ Th cells and subsequently specific antibodies. However, the limited HBc/eAg-specific CD4+ cell priming can effectively be circumvented by prior administration of a recombinant or synthetic form of HBc/eAg in adjuvant.
Sällberg
M
M
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA. masa@vird01.hs.sll.se
Townsend
K
K
Chen
M
M
O'Dea
J
J
Banks
T
T
Jolly
D J
DJ
Chang
S M
SM
Lee
W T
WT
Milich
D R
DR
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005822:Genetic Vectors; D006183:H-2 Antigens / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012190:Retroviridae; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D006183:H-2 Antigens; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA