| Autor: |
Leroux-Roels, Geert, Bourguignon, Patricia, Willekens, Julie, Janssens, Michel, Clement, Frédéric, Didierlaurent, Arnaud M., Fissette, Laurence, Roman, François, Boutriau, Dominique |
| Zdroj: |
Clinical and Vaccine Immunology (formerly CDLI); January 2014, Vol. 21 Issue: 3 p302-311, 10p |
| Abstrakt: |
ABSTRACTThis phase II study evaluated the effect of chloroquine on the specific CD8+T-cell responses to and the safety of a booster dose of investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01Bvaccine containing 10 µg of recombinant fusion protein (F4) adjuvanted with the AS01Badjuvant system. Healthy adults aged 21 to 41 years, primed 3 years before with two F4/AS01Bdoses containing 10 or 30 µg of F4 (ClinicalTrials.govregistration number NCT00434512), were randomized (1:1) to receive the F4/AS01Bbooster administered alone or 2 days after chloroquine (300 mg). F4-specific CD8+/CD4+T-cell responses were characterized by intracellular cytokine staining and lymphoproliferation assays and anti-F4 antibodies by enzyme-linked immunosorbent assays (ELISAs). No effect of chloroquine on CD4+/CD8+T-cell and antibody responses and no vaccine effect on CD8+T-cell responses (cytokine secretion or proliferation) were detected following F4/AS01Bbooster administration. In vitro, chloroquine had a direct inhibitory effect on AS01Badjuvant properties; AS01-induced cytokine production decreased upon coincubation of cells with chloroquine. In the pooled group of participants primed with F4/AS01Bcontaining 10 µg of F4, CD4+T-cell and antibody responses induced by primary vaccination persisted for at least 3 years. The F4/AS01Bbooster induced strong F4-specific CD4+T-cell responses, which persisted for at least 6 months with similar frequencies and polyfunctional phenotypes as following primary vaccination, and high anti-F4 antibody concentrations, reaching higher levels than those following primary vaccination. The F4/AS01Bbooster had a clinically acceptable safety and reactogenicity profile. An F4/AS01Bbooster dose, administered alone or after chloroquine, induced robust antibody and F4-specific CD4+T-cell responses but no significant CD8+T-cell responses (cytokine secretion or proliferation) in healthy adults. (This study has been registered at ClinicalTrials.govunder registration number NCT00972725). |
| Databáze: |
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