Broad HIV-1 inhibition in vitro by vaccine-elicited CD8(+) T cells in African adults.
We are developing a pan-clade HIV-1 T-cell vaccine HIVconsv, which could complement Env vaccines for prophylaxis and be a key to HIV cure. Our strategy focuses vaccine-elicited effector T-cells on functionally and structurally conserved regions (not full-length proteins and not only epitopes) of the HIV-1 proteome, which are common to most global variants and which, if mutated, cause a replicative fitness loss. Our first clinical trial in low risk HIV-1-negative adults in Oxford demonstrated the principle that naturally mostly subdominant epitopes, when taken out of the context of full-length proteins/virus and delivered by potent regimens involving combinations of simian adenovirus and poxvirus modified vaccinia virus Ankara, can induce robust CD8(+) T cells of broad specificities and functions capable of inhibiting in vitro HIV-1 replication. Here and for the first time, we tested this strategy in low risk HIV-1-negative adults in Africa. We showed that the vaccines were well tolerated and induced high frequencies of broadly HIVconsv-specific plurifunctional T cells, which inhibited in vitro viruses from four major clades A, B, C, and D. Because sub-Saharan Africa is globally the region most affected by HIV-1/AIDS, trial HIV-CORE 004 represents an important stage in the path toward efficacy evaluation of this highly rational and promising vaccine strategy.
KAVI-Institute of Clinical Research, University of Nairobi , Kenya ;
Gaudensia
G
Mutua
KAVI-Institute of Clinical Research, University of Nairobi , Kenya ;
Bashir
B
Farah
KAVI-Institute of Clinical Research, University of Nairobi , Kenya ;
Robert
R
Langat
KAVI-Institute of Clinical Research, University of Nairobi , Kenya ;
Jackton
J
Indangasi
KAVI-Institute of Clinical Research, University of Nairobi , Kenya ;
Simon
S
Ogola
KAVI-Institute of Clinical Research, University of Nairobi , Kenya ;
Brian
B
Onsembe
Human Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College , London, UK.
Jakub T
JT
Kopycinski
Human Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College , London, UK.
Peter
P
Hayes
Jenner Institute, University of Oxford , Oxford, UK.
Nicola J
NJ
Borthwick
Human Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College , London, UK.
Ambreen
A
Ashraf
Emmes Corporation , Rockville, Maryland, USA.
Len
L
Dally
Emmes Corporation , Rockville, Maryland, USA.
Burc
B
Barin
Karolinska Institute , Stockholm, Sweden.
Annika
A
Tillander
Human Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College , London, UK.
Jill
J
Gilmour
International AIDS Vaccine Initiative-New York , New York, New York, USA.
Jan
J
De Bont
Jenner Institute, University of Oxford , Oxford, UK.
Alison
A
Crook
ICHOR Medical Systems, Inc. , San Diego, California, USA.
Drew
D
Hannaman
Human Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College , London, UK.
Josephine H
JH
Cox
KAVI-Institute of Clinical Research, University of Nairobi , Kenya ;
Omu
O
Anzala
International AIDS Vaccine Initiative-New York , New York, New York, USA.
Patricia E
PE
Fast
Karolinska Institute , Stockholm, Sweden.
Marie
M
Reilly
International AIDS Vaccine Initiative-New York , New York, New York, USA.
Kundai
K
Chinyenze
KAVI-Institute of Clinical Research, University of Nairobi , Kenya ;
Walter
W
Jaoko
Jenner Institute, University of Oxford, Oxford, UK; International Research Center for Medical Sciences, Kumamoto University, Japan.
Tomáš
T
Hanke
The
T
Hiv-Core 004 Study Group