Peptide-loaded dendritic-cell vaccination followed by treatment interruption for chronic HIV-1 infection: A phase 1 trial

• Published in: Journal of Medical Virology Vol. 78; no. 6; pp. 711 - 718
• Main Authors: Ide, Fuyuaki, Nakamura, Tetsuya, Tomizawa, Mariko, Kawana-Tachikawa, Ai, Odawara, Takashi, Hosoya, Noriaki, Iwamoto, Aikichi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2006; Wiley; Wiley-Liss
• Subjects: Adult; Antiretroviral Therapy, Highly Active; Biological and medical sciences; CD4 Lymphocyte Count; Chronic Disease; Chronic Disease - therapy; Dendritic Cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - transplantation; Drug Resistance, Viral; Drug Resistance, Viral - genetics; Epitopes, T-Lymphocyte; Epitopes, T-Lymphocyte - immunology; Fundamental and applied biological sciences. Psychology; HAART; HIV Antigens; HIV Antigens - administration & dosage; HIV Antigens - immunology; HIV Infections; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - therapy; HIV-1; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunotherapy; Immunotherapy - methods; Infectious diseases; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mutation; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Cytotoxic - immunology; treatment interruption; vaccine; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; HIV-1; Immunopathology; Dendritic cell; Peptides; HIV-1 virus; Vaccination; Retroviridae; AIDS; Vaccine; Immune deficiency; Lentivirus; Infection; Virus; treatment interruption; Chronic; Treatment; Viral disease; Antiviral; Human immunodeficiency virus; HAART
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.20612

Immune response enhanced by therapeutic HIV‐1 vaccine may control viral proliferation after discontinuation of highly active antiretroviral therapy (HAART). Although which strategies for therapeutic vaccination are feasible remains controversial, application of dendritic cells (DCs) as a vaccine adjuvant represents a promising approach to improving deteriorated immune function in HIV‐1‐infected individuals. The safety and efficacy of DC‐based vaccine loaded with HIV‐1‐derived cytotoxic T lymphocytes (CTL) peptides were thus investigated in this study. Autologous DCs loaded with seven CTL peptides with HLA‐A*2402 restriction were immunized to four HIV‐1‐infected individuals under HAART. In terms of safety, peptide‐loaded DCs were well tolerated, and only mild local and general symptoms were observed during vaccine administration. ELISPOT assays to detect IFN‐γ production in CD8+ lymphocytes revealed a limited breadth of responses to immunized peptides in two of four participants, but no response in the remaining two participants. Differences in immunological response might be attributable to the fact that responders displayed higher nadir CD4 counts before starting HAART and were immunized with a larger number of DCs per reactive peptide than non‐responders. Discontinuation of HAART after vaccination failed to lower viral set points compared to those before starting HAART. This early outcome warrants further exploration to elucidate the therapeutic value of vaccination with DCs in HIV‐1 infection. J. Med. Virol. 78:711–718, 2006. © 2006 Wiley‐Liss, Inc.