Design and pre-clinical evaluation of a universal HIV-1 vaccine.
BACKGROUND
One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test.


RESULTS
To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection.


CONCLUSIONS
Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity.
Létourneau
Sven
S
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, United Kingdom.
Im
Eung-Jun
EJ
Mashishi
Tumelo
T
Brereton
Choechoe
C
Bridgeman
Anne
A
Yang
Hongbing
H
Dorrell
Lucy
L
Dong
Tao
T
Korber
Bette
B
McMichael
Andrew J
AJ
Hanke
Tomás
T
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D000939:Epitopes / Q000737:chemistry; D005814:Genes, Viral; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology
D016915:AIDS Vaccines; D000939:Epitopes; D007371:Interferon-gamma