Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: implications for vaccine development.
Despite recent advances in antiviral therapy for human immunodeficiency virus (HIV) infection, successful global intervention will require an effective vaccine. Expanding evidence suggests that cytotoxic T-lymphocyte (CTL) responses will be an important component of such a vaccine. The varying geographic distribution of HIV type 1 (HIV-1) clades, with the relative absence of clade B HIV-1 outside the developed world, is considered a major obstacle to the development of a single efficacious vaccine. An understanding of cross-reactive CTL responses between different HIV-1 clades is crucial in the design of a vaccine which will be broadly immunogenic. In this study, we examined the ability of HIV-1 Gag-, reverse transcriptase-, and Env-specific CTL clones isolated from individuals infected in the United States to recognize non-B clade viral sequences and found that all were cross-reactive with the majority of non-B clade viral sequences tested. We next studied HIV-1-specific CTL responses in African individuals infected with clade A, C, or G virus and evaluated cross-recognition of clade B virus. Of 14 persons evaluated, all demonstrated cross-reactivity with the U.S. clade B viral constructs. We conclude that significant CTL cross-reactivity exists between clade B and non-B epitopes, suggesting that CTL cross-recognition among HIV-1 clades is more widespread than anticipated and that a vaccine based on a single clade may be broadly applicable.
Cao
H
H
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Kanki
P
P
Sankalé
J L
JL
Dieng-Sarr
A
A
Mazzara
G P
GP
Kalams
S A
SA
Korber
B
B
Mboup
S
S
Walker
B D
BD
D000595:Amino Acid Sequence; D001483:Base Sequence; D003429:Cross Reactions; D018604:Epitope Mapping; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D005828:Genetics, Population; D015488:HIV Antigens / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008969:Molecular Sequence Data; D012675:Senegal; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014481:United States; D054311:nef Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015693:Gene Products, nef; D015684:Gene Products, pol; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D006680:HLA Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus