CD8+ T-cell responses to different HIV proteins have discordant associations with viral load.
Selection of T-cell vaccine antigens for chronic persistent viral infections has been largely empirical. To define the relationship, at the population level, between the specificity of the cellular immune response and viral control for a relevant human pathogen, we performed a comprehensive analysis of the 160 dominant CD8(+) T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific responses were associated with lowering viremia. Env-specific and Accessory/Regulatory protein-specific responses were associated with higher viremia. Increasing breadth of Gag-specific responses was associated with decreasing viremia and increasing Env breadth with increasing viremia. Association of the specific CD8(+) T-cell response with low viremia was independent of HLA type and unrelated to epitope sequence conservation. These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation.
Kiepiela
Photini
P
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban 4013, South Africa.
Ngumbela
Kholiswa
K
Thobakgale
Christina
C
Ramduth
Dhanwanthie
D
Honeyborne
Isobella
I
Moodley
Eshia
E
Reddy
Shabashini
S
de Pierres
Chantal
C
Mncube
Zenele
Z
Mkhwanazi
Nompumelelo
N
Bishop
Karen
K
van der Stok
Mary
M
Nair
Kriebashnie
K
Khan
Nasreen
N
Crawford
Hayley
H
Payne
Rebecca
R
Leslie
Alasdair
A
Prado
Julia
J
Prendergast
Andrew
A
Frater
John
J
McCarthy
Noel
N
Brander
Christian
C
Learn
Gerald H
GH
Nickle
David
D
Rousseau
Christine
C
Coovadia
Hoosen
H
Mullins
James I
JI
Heckerman
David
D
Walker
Bruce D
BD
Goulder
Philip
P
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D013019:South Africa; D019562:Viral Load; D014764:Viral Proteins / Q000378:metabolism*; D014766:Viremia / Q000276:immunology / Q000378:metabolism
D015686:Gene Products, env; D015683:Gene Products, gag; D006680:HLA Antigens; D014764:Viral Proteins