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A dendritic cell‐based vaccine for treating HIV infection: background and preliminary results
Author(s) -
Andrieu J. M.,
Lu W.
Publication year - 2007
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.2006.01738.x
Subject(s) - viral load , simian immunodeficiency virus , virology , immunology , immune system , medicine , virus , cd8 , vaccination , viral replication , t cell , viremia , antibody , dendritic cell
. 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.