A dendritic cell-based vaccine for treating HIV infection: background and preliminary results.
Antibody response against human immunodeficiency virus-1 (HIV) is ineffective and cellular immune response is not strong enough to achieve the complete suppression or at least a strong control of viral replication in HIV- infected patients. In 2001, we showed in vitro that dendritic cells (DCs) of HIV-infected patients loaded with autologous HIV chemically inactivated by aldrithiol-2 were capable of raising an HIV-specific cellular immune response powerful enough to allow the destruction of autologous HIV- infected CD4 T cells. In 2003, we showed that simian immunodeficiency virus (SIV)-infected macaques vaccinated with inactivated SIV-loaded autologous DCs raised a strong SIV-specific cellular response. Ten months after vaccination, plasma viral load of 7 out of the 10 vaccinated monkeys remained 1000-fold lower than initially. In December 2004, we published results observed in 18 untreated HIV-infected patients vaccinated with autologous monocyte-derived DCs loaded with autologous inactivated HIV. A year following vaccination, 8 patients had a plasma viral load decrease >90%; among them, 4 had viral load <1000 copies mL(-1). Moreover, by one year, the viral load decline of the 18 patients was significantly correlated with their percentage of HIV-1-gag-specific CD8(+) T cells expressing perforin and that of HIV-1-specific CD4(+) T(H)1 cells. This is the first demonstration of the capacity of a therapeutic vaccine to induce an effective HIV-specific T cell response associated with sustained viral suppression in untreated viremic patients. The manipulation of antigen presenting cells to elicit virus-specific cellular responses is a promising tool to control persistant viral infections.
Andrieu
J M
JM
Institut de Recherche sur les Vaccins et l'Immunothérapie des Cancers et du SIDA (IRVICS), Centre Biomédical des Saints Pères, Université de Paris V, Paris, France. j.m.andrieu@orange.fr
Lu
W
W
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation* / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008251:Macaca; D018449:SAIDS Vaccines; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus; D015164:Vaccines, Inactivated; D019562:Viral Load
D018449:SAIDS Vaccines; D015164:Vaccines, Inactivated