Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers

Evaluation of the Safety and Immunogenicity of Two Antigen Concentrations of the Mtb72F/AS02ACandidate Tuberculosis Vaccine in Purified Protein Derivative-Negative Adults

“…All AEs reported were transient, and most resolved within 1 to 4 days. The pattern of AEs observed has previously been reported with other vaccines containing AS02 A (14,16,37,(40)(41)(42). No clinically significant changes in laboratory test (biochemistry and hematology) values related to vaccination were observed.…”

Immunogenicity and Safety of a Booster Dose of an Investigational Adjuvanted Polyprotein HIV-1 Vaccine in Healthy Adults and Effect of Administration of Chloroquine

“…The booster dose of the F4/AS01 B vaccine induced a strong F4-specific CD4 ϩ T-cell recall response, which persisted for at least 6 months, had approximately the same frequency and exhibited a similar polyfunctional phenotype as that observed following primary vaccination. Strong and persistent CD4 ϩ T-cell responses were also induced by the F4/AS01 B vaccine (16) or by a previous HIV-1 vaccine candidate comprising gp120 and a Nef-Tat fusion protein in healthy adults and in subjects with HIV-1 infection (2,(17)(18)(19). These findings are important since the presence of polyfunctional and persistent HIV-specific CD4 ϩ T cells in HIV-infected individuals is associated with long-term nonprogression (11,(34)(35)(36).…”

“…The efficacy of this vaccine in reducing viral load was specifically assessed in a phase IIb, proof-of-concept trial (ClinicalTrials.gov registration number NCT01218113), but results are not available yet. An earlier formulation of this vaccine, composed of three HIV-1 viral antigens (gp120, Nef, and Tat) and the AS02 A adjuvant system, was previously shown to induce a transient increase of gp120-specific CD8 ϩ T-cell proliferation in healthy adults and in adults with well-controlled chronic HIV-1 infection treated with highly active antiretroviral therapy (2,18,19).…”

Immunoprevalence of the CD4+ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

“…Current approaches are mainly based on the introduction of structural antigens into viral vectors, their combination with strong adjuvants or their injection as DNA vaccine [1]. Alternative or complementary approaches aim at neutralizing accessory or regulatory proteins because they disturb the immune system and counteract its beneficial role [2,3]. Transacting protein (Tat) is a small regulatory protein that is expressed early in the viral cycle and is essential for viral replication [4].…”

“…It is not known whether immune response specific for accessory or regulatory HIV proteins leads to immune escape, which has a fitness cost on the virus. Moreover, despite the requirement of CD4 1 T lymphocytes to sustain both humoral and cellular responses, the CD4 1 T-cell response specific for Tat and Vpr is poorly documented in humans [3,19], in contrast to other HIV proteins [20][21][22].…”