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*
Swedish Institute for Infectious Disease Control, Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden;
Department of Dermatovenereology, South Hospital, Stockholm, Sweden;
Section of Retroviral Immunology, Food and Drug Administration, Bethesda, MD 20892; and
§
Department of Surgery, Duke University Medical Center, Durham, NC 27710
Intensive chemotherapy is capable of reducing the viral load in
HIV-1-infected individuals while infected cells are still present. A
special property of DNA immunization is to induce both new CTL and Ab
responses. We evaluated the possibility of inducing new immune
responses in already infected individuals by means of DNA constructs
encoding the nef, rev, or
tat regulatory HIV-1 genes. Significant changes in viral
loads and CD4+ counts were observed in four patients who
started highly active antiretroviral treatment (HAART) during the
immunization study. The DNA immunization induced Ag-specific T cell
proliferation, which persisted up to 9 mo after the last DNA injection,
and cytolytic activities but did not, by itself, reduce viral load.
Increased levels of CTL precursor cells were induced in all nine
DNA-immunized patients. The profile of IFN-
secretion observed when
human PBMC were transfected with the nef,
rev, and tat DNA resembled that found in
the CTL activity (nef > tat >
rev). Ab responses that occurred after immunizations
were of a low magnitude. In accordance with the high IL-6 production
induced by the nef DNA plasmid, IgG titers were highest
in patients immunized with nef DNA. The initiation of
HAART appears to contribute to the induction of new HIV-specific CTL
responses, but by itself did not cause obvious re-induction of these
activities.
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