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
Immunogenicity and Safety of a Booster Dose of an Investigational Adjuvanted Polyprotein HIV-1 Vaccine in Healthy Adults and Effect of Administration of Chloroquine Geert Leroux-Roels a , Patricia Bourguignon b , Julie Willekens a , Michel Janssens b , Frédéric Clement a , Arnaud M. Didierlaurent b , Laurence Fissette b , François Roman b and Dominique Boutriau b a Center for Vaccinology, Ghent University, Ghent, Belgium b GlaxoSmithKline Vaccines, Rixensart, Belgium M. F. Pasetti , Editor 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).