Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients.
BACKGROUND
DNA vaccination is known to generate immune responses against HIV-1 in animal models. We aimed to assess the efficacy of DNA vaccination in induction of immune responses in HIV-1-infected human beings.


METHODS
Nine symptom-free HIV-1-infected patients were immunised with DNA constructs encoding the nef, rev, or tat regulatory genes of HIV-1. The patients were selected for having no or low antibody reactivities to these antigens. HIV-1-specific cytotoxic T-lymphocytes (CTLs), precursor frequencies, and antigen-specific proliferative responses were measured before, during, and after three immunisations over 6 months.


RESULTS
Cellular immune reactivities against the HIV-1 regulatory proteins were absent or low before DNA immunisation. DNA vaccination induced detectable memory cells in all patients and specific cytotoxicity in eight patients. CTLs were MHC-class-I restricted and mainly of CD8+ origin. In three patients the cellular activity was transient, decreasing after an initial response.


CONCLUSIONS
DNA immunisation with HIV-1 genes can induce specific cellular responses in human beings with no apparent side-effects. It is theoretically possible that HIV-1-specific cytotoxic responses to regulatory proteins could lead to infected cells being eliminated before they have released new viral particles. However, it is possible that the patients we selected responded less than would non-selected or non-infected individuals. The small number of patients presented here does not allow generalisation of our findings.
Calarota
S
S
Microbiology and Tumourbiology Center, Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm.
Bratt
G
G
Nordlund
S
S
Hinkula
J
J
Leandersson
A C
AC
Sandström
E
E
Wahren
B
B
D016915:AIDS Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004279:DNA, Viral / Q000276:immunology; D005809:Genes, Regulator / Q000276:immunology; D005814:Genes, Viral / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D016915:AIDS Vaccines; D004279:DNA, Viral; D019444:Vaccines, DNA