Cross-reactivity of anti-HIV-1 T cell immune responses among the major HIV-1 clades in HIV-1-positive individuals from 4 continents.
BACKGROUND
The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades.


METHODS
Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon- gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1.


RESULTS
Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62-0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001).


CONCLUSIONS
Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.
Coplan
Paul M
PM
Merck Research Laboratories, West Point, Pennsylvania, USA. pcoplan@ipm-microbicides.org
Gupta
Swati B
SB
Dubey
Sheri A
SA
Pitisuttithum
Punnee
P
Nikas
Alex
A
Mbewe
Bernard
B
Vardas
Efthyia
E
Schechter
Mauro
M
Kallas
Esper G
EG
Freed
Dan C
DC
Fu
Tong-Ming
TM
Mast
Christopher T
CT
Puthavathana
Pilaipan
P
Kublin
James
J
Brown Collins
Kelly
K
Chisi
John
J
Pendame
Richard
R
Thaler
Scott J
SJ
Gray
Glenda
G
Mcintyre
James
J
Straus
Walter L
WL
Condra
Jon H
JH
Mehrotra
Devan V
DV
Guess
Harry A
HA
Emini
Emilio A
EA
Shiver
John W
JW
D000328:Adult; D016384:Consensus Sequence; D003429:Cross Reactions; D005260:Female; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics; D005843:Geography; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus