Improving on the ability of endogenous hepatitis B core antigen to prime cytotoxic T lymphocytes.
Hepatitis B virus core antigen (HBcAg) is thought to be a major target for specific cytotoxic T cells (CTLs) in hepatitis B virus infections. A single dose of hepatitis C virus nonstructural 3/4A DNA (<5 microg) effectively primes functional specific CTLs, independently of CD4(+) T helper cells and by different routes of immunization. In contrast, HBcAg-specific CTL priming was T helper cell dependent and highly sensitive to the dose and route of delivery. Although CTL priming was improved 10-fold by codon optimization and in vivo electroporation, low levels of DNA still failed to prime CTLs effectively. Only high doses (5 microg) of codon-optimized HBcAg delivered by in vivo electroporation primed in vivo lytic and polyfunctional CTLs. The ability of endogenous HBcAg to prime CTLs is surprisingly inefficient and differs from that of nonstructural 3/4A. This has important implications for the design of HBcAg-based therapeutic vaccines in humans.
Nyström
Jessica
J
Division of Clinical Microbiology, of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Chen
Antony
A
Frelin
Lars
L
Ahlén
Gustaf
G
Koh
Sarene
S
Brass
Anette
A
Peterson
Darrell L
DL
Fons
Michael
M
Milich
David R
DR
Hultgren
Catharina
C
Sällberg
Matti
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D018274:Electroporation; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus