Therapeutic vaccination expands and improves the function of the HIV-specific
memory T-cell repertoire.
Author(s): Casazza JP(1), Bowman KA, Adzaku S, Smith EC, Enama ME, Bailer RT, Price DA,
Gostick E, Gordon IJ, Ambrozak DR, Nason MC, Roederer M, Andrews CA, Maldarelli
FM, Wiegand A, Kearney MF, Persaud D, Ziemniak C, Gottardo R, Ledgerwood JE,
Graham BS, Koup RA; VRC 101 Study Team.
Collaborators: Holman L, Hendel C, Plummer S, Novik L, Larkin B, Rucker S,
Costner P, Goswami T, Read S, Leitman S, Decederfelt H, Starling J, Alley T,
Jones R, Johnson D, Jones S, Sitar S, Stanford LC, Washington-Lewis R, Thompson
E, Rhone K, Zaia P.
Affiliation(s): Author information:
(1)Vaccine Research Center, National Institute of Allergy and Infectious Diseases,
National Institutes of Health (NIH),Bethesda, Maryland 20892, USA.
Publication date & source: 2013, J Infect Dis. , 207(12):1829-40
BACKGROUND: The licensing of herpes zoster vaccine has demonstrated that
therapeutic vaccination can help control chronic viral infection. Unfortunately,
human trials of immunodeficiency virus (HIV) vaccine have shown only marginal
efficacy.
METHODS: In this double-blind study, 17 HIV-infected individuals with viral loads
of <50 copies/mL and CD4(+) T-cell counts of >350 cells/µL were randomly assigned
to the vaccine or placebo arm. Vaccine recipients received 3 intramuscular
injections of HIV DNA (4 mg) coding for clade B Gag, Pol, and Nef and clade A, B,
and C Env, followed by a replication-deficient adenovirus type 5 boost (10(10)
particle units) encoding all DNA vaccine antigens except Nef. Humoral, total
T-cell, and CD8(+) cytotoxic T-lymphocyte (CTL) responses were studied before and
after vaccination. Single-copy viral loads and frequencies of latently infected
CD4(+) T cells were determined.
RESULTS: Vaccination was safe and well tolerated. Significantly stronger
HIV-specific T-cell responses against Gag, Pol, and Env, with increased
polyfunctionality and a broadened epitope-specific CTL repertoire, were observed
after vaccination. No changes in single-copy viral load or the frequency of
latent infection were observed.
CONCLUSIONS: Vaccination of individuals with existing HIV-specific immunity
improved the magnitude, breadth, and polyfunctionality of HIV-specific memory
T-cell responses but did not impact markers of viral control.
CLINICAL TRIALS REGISTRATION: NCT00270465.
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