Long-term increase of CD4+ central memory cells in HIV-1-infected individuals by therapeutic HIV-1 rgp160 immunization.
OBJECTIVE
To evaluate functional potential and phenotypic markers in HIV-1-infected patients immunized with HIV-1 rgp160.


METHODS
We assessed changes in T-cell phenotype and immune function in 12 HIV-1-infected individuals that were part of a therapeutic vaccine study from 1992 to 1995 [Sandstrom E, Wahren B. Therapeutic immunisation with recombinant gp160 in HIV-1 infection: a randomised double-blind placebo-controlled trial. Nordic VAC-04 Study Group. Lancet 1999;353(9166):1735-42]. The patients received 160 microg HIV-1 rgp160 or placebo i.m. at baseline (day 0), and months 1, 2, 3, 4, 6, and thereafter every 3 months. Frozen peripheral blood mononuclear cells (PBMC) were retrieved from time points 0, 9, 12 and 24 months for phenotypic analysis utilizing flow cytometry.


RESULTS
Up-regulation of immune activation markers HLA-DR and CD38 was observed at baseline and throughout the monitoring period on both CD4+ and CD8+ T cells in all patients, reflecting immune activation due to persistent high viral load. Further enhanced expression of activation markers was observed over time in the vaccine group, but not the placebo group. We also observed a consistent long-term increase of the CD4+ central memory population (CD3+CD4+CD45RA-CCR7+) in the vaccinated group.


CONCLUSIONS
Administration of eight doses of rgp160 in a year appeared to partially reverse some of the defects exerted by HIV-1 on the immune system. A combination of vaccination with effective antiretroviral therapy (ART) may thus represent an immunotherapeutic intervention for treatment of chronic HIV-1 infection. The improvement of a HIV-1-specific central memory population and HIV-1 antigen-specific CD4+ lymphoproliferative responses may have contributed to the short-term improved survival reported in the vaccinated group.
Gudmundsdotter
Lindvi
L
Department of Virology, Swedish Institute for Infectious Disease Control, Solna, Sweden. l.gudmundsdotter@smi.ki.se
Boström
Ann-Charlotte
AC
Burton
Catherine
C
Rosignoli
Guglielmo
G
Sandström
Eric
E
Hejdeman
Bo
B
Wahren
Britta
B
Imami
Nesrina
N
Gotch
Frances
F
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D013997:Time Factors
D016915:AIDS Vaccines; D019302:HIV Envelope Protein gp160; D011994:Recombinant Proteins