Abstract
BackgroundVacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.MethodsSafety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.ResultsVacc-4x proliferative T cell responses increased only among the vaccinated (p≤0.031). The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037) and developed larger DTH (p = 0.005) than the adjuvant group. Rectal (distal) Vacc-4x IgA and IgG antibodies also increased (p = 0.043) in this group. In contrast, the high dose generated higher nasal (local) Vacc-4x IgA (p = 0.028) and serum IgG (p = 0.030) antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = −0.82, p<0.001) and high regulation (r = 0.61, p = 0.010) at baseline.ConclusionIntranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.Trial RegistrationClinicalTrials.gov NCT01473810
Highlights
Human Immunodeficiency Virus (HIV) type 1 infection is a challenge for global health [1]
Strengthened HIV-specific cellular immune responses attained by therapeutic vaccination may be essential as part of a future functional cure for HIV [6,7,8]
Vacc-4x is a peptide-based therapeutic HIV vaccine corresponding to conserved regions of Gag p24 [10]
Summary
Human Immunodeficiency Virus (HIV) type 1 infection is a challenge for global health [1]. Therapeutic HIV vaccines are designed to induce more effective HIV-specific immune responses [4]. HIV protein Gag-specific T cell responses are associated with virus control and delayed disease progression [9]. Intradermal Vacc-4x with recombinant granulocyte-macrophage colony stimulating factor as adjuvant has been shown to enhance HIV-specific cellular immune responses in patients on ART [11], induce long lasting vaccine-specific T cell memory [12] and lower viral load set-points after interruption of ART [13]. Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant
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