Intranasal administration of a therapeutic HIV vaccine (Vacc-4x) induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.
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-β.


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.


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov NCT01473810.
Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
Kristin
K
Brekke
Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
Andreas
A
Lind
Norwegian Institute of Public Health, Oslo, Norway.
Carol
C
Holm-Hansen
Norwegian Institute of Public Health, Oslo, Norway.
Inger Lise
IL
Haugen
Bionor Pharma, Oslo, Norway.
Birger
B
Sørensen
Bionor Pharma, Oslo, Norway.
Maja
M
Sommerfelt
Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway; University of Oslo, Oslo, Norway.
Dag
D
Kvale
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000494:pharmacology*; D000281:Administration, Intranasal; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000276:immunology; D019562:Viral Load / Q000187:drug effects
D016915:AIDS Vaccines; D016212:Transforming Growth Factor beta; C494182:Vacc-4x; D016753:Interleukin-10