A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans.
The immunogenicities of candidate DNA- and modified vaccinia virus Ankara (MVA)-vectored human immunodeficiency virus (HIV) vaccines were evaluated on their own and in a prime-boost regimen in phase I clinical trials in healthy uninfected individuals in the United Kingdom. Given the current lack of approaches capable of inducing broad HIV-neutralizing antibodies, the pTHr.HIVA DNA and MVA.HIVA vaccines focus solely on the induction of cell-mediated immunity. The vaccines expressed a common immunogen, HIVA, which consists of consensus HIV-1 clade A Gag p24/p17 proteins fused to a string of clade A-derived epitopes recognized by cytotoxic T lymphocytes (CTLs). Volunteers' fresh peripheral blood mononuclear cells were tested for HIV-specific responses in a validated gamma interferon enzyme-linked immunospot (ELISPOT) assay using four overlapping peptide pools across the Gag domain and three pools of known CTL epitopes present in all of the HIVA protein. Both the DNA and the MVA vaccines alone and in a DNA prime-MVA boost combination were safe and induced HIV-specific responses in 14 out of 18, seven out of eight and eight out of nine volunteers, respectively. These results are very encouraging and justify further vaccine development.
Mwau
Matilu
M
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Cebere
Inese
I
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Sutton
Julian
J
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Chikoti
Priscilla
P
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Winstone
Nicola
N
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Wee
Edmund G-T
EG
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Beattie
Tara
T
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Chen
Yun-Hsiang
YH
University of St Andrews, School of Biology, St Andrews, UK.
Dorrell
Lucy
L
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
McShane
Helen
H
Nuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Schmidt
Claudia
C
International AIDS Vaccine Initiative, 110 William Street, New York, NY 10038, USA.
Brooks
Mary
M
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Patel
Sandip
S
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Roberts
Joanna
J
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Conlon
Christopher
C
Nuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Rowland-Jones
Sarah L
SL
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Bwayo
Job J
JJ
Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
McMichael
Andrew J
AJ
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Hanke
Tomáš
T
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
D016915:AIDS Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D005260:Female; D015683:Gene Products, gag; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D015488:HIV Antigens; D016655:HIV Core Protein p24; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1