title: Immunogenicity and safety of a booster dose of an investigational adjuvanted polyprotein HIV-1 vaccine in healthy adults and effect of administration of chloroquine.
abstract: This 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/AS01(B) vaccine containing 10 μg of recombinant fusion protein (F4) adjuvanted with the AS01(B) adjuvant system. Healthy adults aged 21 to 41 years, primed 3 years before with two F4/AS01(B) doses containing 10 or 30 μg of F4 (ClinicalTrials.gov registration number NCT00434512), were randomized (1:1) to receive the F4/AS01(B) booster 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/AS01(B) booster administration. In vitro, chloroquine had a direct inhibitory effect on AS01(B) adjuvant properties; AS01-induced cytokine production decreased upon coincubation of cells with chloroquine. In the pooled group of participants primed with F4/AS01(B) containing 10 μg of F4, CD4(+) T-cell and antibody responses induced by primary vaccination persisted for at least 3 years. The F4/AS01(B) booster 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/AS01(B) booster had a clinically acceptable safety and reactogenicity profile. An F4/AS01(B) booster 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.gov under registration number NCT00972725).
authors.affiliation: Center for Vaccinology, Ghent University, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Patricia
authors.initials: P
authors.lastname: Bourguignon
authors.forename: Julie
authors.initials: J
authors.lastname: Willekens
authors.forename: Michel
authors.initials: M
authors.lastname: Janssens
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clement
authors.forename: Arnaud M
authors.initials: AM
authors.lastname: Didierlaurent
authors.forename: Laurence
authors.initials: L
authors.lastname: Fissette
authors.forename: François
authors.initials: F
authors.lastname: Roman
authors.forename: Dominique
authors.initials: D
authors.lastname: Boutriau
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002738:Chloroquine / Q000008:administration & dosage*; D016207:Cytokines / Q000096:biosynthesis; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D008297:Male; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000962:Antimalarials; D016207:Cytokines; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins; D002738:Chloroquine