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

• Published in: PloS one Vol. 9; no. 11; p. e112556
• Main Authors: Brekke, Kristin, Lind, Andreas, Holm-Hansen, Carol, Haugen, Inger Lise, Sørensen, Birger, Sommerfelt, Maja, Kvale, Dag
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.11.2014; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Administration, Intranasal; AIDS; AIDS vaccines; AIDS Vaccines - administration & dosage; AIDS Vaccines - pharmacology; Analysis; Antibodies; Antigens; Biology and Life Sciences; Bone morphogenetic proteins; CD4 antigen; CD8 antigen; Control; Cytokines; Dose-Response Relationship, Immunologic; Drug resistance; Enzyme-Linked Immunosorbent Assay; Health aspects; HIV; Hospitals; Human immunodeficiency virus; Humans; Immune response; Immunity; Immunity, Mucosal - drug effects; Immunity, Mucosal - immunology; Immunogenicity; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; Immunoregulation; In vivo methods and tests; Infections; Infectious diseases; Interleukin 10; Interleukin-10 - immunology; Intranasal administration; Lactoferrin; Lymphocytes; Lymphocytes T; Mucosal immunity; Peptides; Public health; Randomization; Rectum; Secretions; Skin; Skin tests; Statistics, Nonparametric; T cell receptors; T cells; Transforming Growth Factor beta - immunology; Transforming growth factors; Vaccination; Vaccines; Viral Load - drug effects; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112556

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. 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. 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. 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. ClinicalTrials.gov NCT01473810.