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Cytolitic and Non-cytolitic Antiviral Mechanisms Elicited by HIV-1 Whole Inactivated Vaccine in HAART-naïve, Asymptomatic HIV-infected Individuals
D Trabattoni1, A Gori2, R Maserati3, G Rizzardini4, C Fenizia1, A Marino1, F Mazzotta5, G Theofan6, D Bray7, and Mario Clerici*1
1Univ of Milan, Italy; 2Hosp L Sacco, Milano, Italy; 3IRCCS Policlin San Matteo, Pavia, Italy; 4Hosp di Circolo, Busto Arsizio, Italy; 5Hosp SM Annunziata, Florence, Italy; 6Immune Response, Carlsbad, CA, US; and 7Med Res Council, London, UK
Background: Use of agents
that increase immune response to HIV is being considered to delay initiation of
ART in subjects who are therapy naïve. We evaluated the ability of Remune, a
whole inactivated HIV-1 vaccine of gp120-depleted HIV antigen emulsified in
Incomplete Freund’s Adjuvant (IFA), to elicit cytolitic (measured by ELIspot)
and non-cytolitic (measured by a-defensin production) antiviral mechanisms
in antiretroviral-naive, asymptomatic HIV-1-infected subjects.
Methods: Native p24- (np24), gag-, and env-specific interferon-g
(IFN-g)-secreting CD8+ T cells (ELISpot), as well
as mitogen-stimulated a-defensin production (ELISA) were evaluated at
different times after immunization, in subjects with HIV-1 RNA 10,000 to 40,000
copies/mL and CD4 400 to 800 cells/mL. Patients were randomized to receive
either 3 injection of Remune at
baseline, week 12 and week 24 (n = 19), (Group A); a single injection of
Remune at baseline (n = 11)(Group B);
IFA (n = 10); or saline (n = 11).
Results: Gag-specific, IFN-g-secreting
CD8+ T cells as well as mitogen-stimulated a-defensin
production were augmented (medians: +61 spot-forming
units [SFU] x 106 peripheral blood mononuclear cells [PBMC] and +1575 pg/mL,
respectively) at week 24 in
Remune A patients, but diminished in all other groups of individuals. The
modifications observed in these patients were accompanied by the stabilization
of absolute CD4 counts, whereas no significant differences were seen in HIV
plasma viremia. An increase in central memory (CCR7+/Remune A)
and a decrease in effector memory (CCR7/RA) CD4 T cells
was also observed in Remune A patients.
Conclusions: Remune elicits
both cytolitic and non-cytolitic antiviral mechanisms in ART-naive,
asymptomatic HIV-1-infected subjects. The short duration of the trial did not
allow the detection of changes in plasma viremia. Nevertheless, because effector
memory reverts to central memory in the presence of low antigenic load, these data, along with the
stabilization of CD4 counts seen in these individuals, suggest that Remune could lower
extraplasmatic (i.e. tissue) HIV viremia.
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