Identification of CD4+ and CD8+ T cell epitopes of woodchuck hepatitis virus core and surface antigens in BALB/c mice.
A therapeutic vaccine against chronic hepatitis B virus (HBV) infection requires the development of a strong and multispecific Th1 cell immune response. Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) closely resemble HBV infection and represent the best animal model for this hepadnavirus-induced disease. Using the BIMAS "HLA Peptide Binding Predictions" program, we have identified and further characterized novel H-2 d-restricted CD8+ epitopes within the WHV core (peptides C#12-21, C#18-32, C#19-27, C#61-69) and surface antigens (peptides preS2#10-18, preS2#27-35, S#76-84, S#133-140 and S#257-265), respectively. These peptides bind to H-2 d with high efficiency and upon immunization of mice with peptide and Freund's adjuvant they induce the development of IFN-gamma producing T cells. More importantly, WHV core peptides C#19-27 and C#61-69 and WHV surface peptides S#133-140 and S#257-265 were also recognized by CD8+ T cells after immunization of mice with DNA/PEI nanoparticles. Direct stimulation of splenocytes obtained from such DNA-immunized mice with peptides C#18-32, S#76-84, and S#257-265 resulted in significant production of IFN-gamma. Thus, we have identified T cell determinants in mice from WHV core and surface antigens that have important value for designing and evaluating an effective vaccine against hepadnavirus infection.
Ochoa-Callejero
L
L
Laboratory of Gene Therapy of Viral Hepatitis, Division of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA), Pamplona, Navarra, Spain.
Otano
I
I
Vales
A
A
Olagüe
C
C
Sarobe
P
P
Lasarte
J J
JJ
Prieto
J
J
Menne
S
S
González-Aseguinolaza
G
G
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D018963:Hepatitis Antigens / Q000276:immunology*; D017919:Hepatitis B Virus, Woodchuck / Q000276:immunology*; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D014758:Viral Core Proteins / Q000276:immunology*
D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D018963:Hepatitis Antigens; D014758:Viral Core Proteins