Immunogenicity of a human immunodeficiency virus (HIV) polytope vaccine containing multiple HLA A2 HIV CD8(+) cytotoxic T-cell epitopes.
Compelling evidence now suggests that alphabeta CD8 cytotoxic T lymphocytes (CTL) have an important role in preventing human immunodeficiency virus (HIV) infection and/or slowing progression to AIDS. Here, we describe an HIV type 1 CTL polyepitope, or polytope, vaccine comprising seven contiguous minimal HLA A2-restricted CD8 CTL epitopes conjoined in a single artificial construct. Epitope-specific CTL lines derived from HIV-infected individuals were able to recognize every epitope within the construct, and HLA A2-transgenic mice immunized with a recombinant virus vaccine coding for the HIV polytope also generated CTL specific for different epitopes. Each epitope in the polytope construct was therefore processed and presented, illustrating the feasibility of the polytope approach for HIV vaccine design. By simultaneously inducing CTL specific for different epitopes, an HIV polytope vaccine might generate activity against multiple challenge isolates and/or preempt the formation of CTL escape mutants.
Woodberry
T
T
Australian Centre for International & Tropical Health & Nutrition, Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Brisbane, Australia.
Gardner
J
J
Mateo
L
L
Eisen
D
D
Medveczky
J
J
Ramshaw
I A
IA
Thomson
S A
SA
Ffrench
R A
RA
Elliott
S L
SL
Firat
H
H
Lemonnier
F A
FA
Suhrbier
A
A
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D015693:Gene Products, nef / Q000276:immunology*; D015684:Gene Products, pol / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014158:Transcription, Genetic; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015693:Gene Products, nef; D015684:Gene Products, pol; D015789:HLA-A2 Antigen; D054311:nef Gene Products, Human Immunodeficiency Virus