Intranasal Administration of a Therapeutic HIV Vaccine (Vacc-4x) Induces Dose-Dependent Systemic and Mucosal Immune Responses in a Randomized Controlled Trial.

PloS one

PubMedID: 25398137

Brekke K, Lind A, Holm-Hansen C, Haugen IL, Sørensen B, Sommerfelt M, Kvale D. Intranasal Administration of a Therapeutic HIV Vaccine (Vacc-4x) Induces Dose-Dependent Systemic and Mucosal Immune Responses in a Randomized Controlled Trial. PLoS ONE. 2014;9(11):e112556.
BACKGROUND
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.

METHODS
Safety 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-ß.

RESULTS
Vacc-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.

CONCLUSION
Intranasal 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 REGISTRATION
ClinicalTrials.gov NCT01473810.