Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination.
Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8(+) T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8(+) T cells capable of this activity are clearly understood; consequently, little is known regarding the ability of vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined CD8(+) T-cell subsets in combination with a highly standardized virus inhibition assay to evaluate CD8(+) T-cell-mediated inhibition of viral replication. Here we show that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8(+) T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes. As it did for chronically infected virus controllers, this activity correlated with HIV-1-specific CD107a or macrophage inflammatory protein 1beta (MIP-1beta) expression from HIV-1-specific T cells. Moreover, for vaccinees or virus controllers, purified memory CD8(+) T cells from a wide range of differentiation stages were capable of significantly inhibiting virus replication. Our data define attributes of an antiviral CD8(+) T-cell response that may be optimized in the search for an efficacious HIV-1 vaccine.
Freel
Stephanie A
SA
Duke University Human Vaccine Institute, Departments of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Lamoreaux
Laurie
L
Chattopadhyay
Pratip K
PK
Saunders
Kevin
K
Zarkowsky
David
D
Overman
R Glenn
RG
Ochsenbauer
Christina
C
Edmonds
Tara G
TG
Kappes
John C
JC
Cunningham
Coleen K
CK
Denny
Thomas N
TN
Weinhold
Kent J
KJ
Ferrari
Guido
G
Haynes
Barton F
BF
Koup
Richard A
RA
Graham
Barney S
BS
Roederer
Mario
M
Tomaras
Georgia D
GD
D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014161:Transduction, Genetic; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology
D016915:AIDS Vaccines; D019444:Vaccines, DNA