Induction of T-cell immunity to antiretroviral drug-resistant human immunodeficiency virus type 1.
Antiretroviral drug-resistant human immunodeficiency virus type 1 (HIV-1) is a major, growing, public health problem. Immune responses targeting epitopes spanning drug resistance sites could ameliorate development of drug resistance. We studied 25 individuals harboring multidrug-resistant HIV-1 for T-cell immunity to HIV-1 proteins and peptides spanning all common drug resistance mutations. CD8 T cells targeting epitopes spanning drug-induced mutations were detected but only in the 3 individuals with robust HIV-specific T-cell activity. Novel CD8 T-cell responses were detected against the common L63P and L10I protease inhibitor fitness mutations. Induction of T-cell immunity to drug-resistant variants was demonstrated in simian human immunodeficiency virus-infected macaques, where both CD8 and CD4 T-cell immune responses to reverse transcriptase and protease antiretroviral mutations were elicited using a novel peptide-based immunotherapy. T-cell responses to antiretroviral resistance mutations were strongest in the most immunocompetent animals. This study suggests feasible strategies to further evaluate the potential of limiting antiretroviral drug resistance through induction of T-cell immunity.
Stratov
Ivan
I
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
Dale
C Jane
CJ
Chea
Socheata
S
McCluskey
James
J
Kent
Stephen J
SJ
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy / Q000821:virology
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D010455:Peptides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease