Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime.
Human immunodeficiency virus (HIV) vaccine candidates were previously constructed as a string of cytotoxic T lymphocyte (CTL) epitopes delivered and expressed using DNA and modified virus Ankara (MVA; an attenuated vaccinia virus) vectors. These vaccines were shown to induce interferon (IFN)-gamma-producing and cytolytic CD8+ T cells after a single vaccine administration. In the course of this work, immunization protocols were sought which would improve the levels of induced HIV-specific T cells. It was found that previous immunological exposure to MVA reduced the efficiency of subsequent priming and boosting using the same vaccine vehicle. However, a combined regime whereby the animals were first primed with the DNA vaccine and then boosted with MVA was the most potent protocol for the induction of both interferon-gamma-producing and cytolytic T cells against two CTL epitopes simultaneously. The general applicability of this novel vaccination method for induction of major histocompatibility complex class I-restricted T cells is discussed.
Hanke
T
T
Molecular Immunology Group, University of Oxford, John Radcliffe Hospital, U.K.
Blanchard
T J
TJ
Schneider
J
J
Hannan
C M
CM
Becker
M
M
Gilbert
S C
SC
Hill
A V
AV
Smith
G L
GL
McMichael
A
A
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004279:DNA, Viral; D000939:Epitopes; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007117:Immunization, Secondary; D007369:Interferon Inducers; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014613:Vaccines, Attenuated; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines
D004279:DNA, Viral; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007369:Interferon Inducers; D010455:Peptides; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D007371:Interferon-gamma