title: Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.
abstract: Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101). Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01084343.
authors: Center for Vaccinology (CEVAC), Ghent University Hospital, Ghent, Belgium.
authors: Geert
authors: G
authors: Leroux-Roels
authors: Cathy
authors: C
authors: Maes
authors: Frédéric
authors: F
authors: Clement
authors: Frank
authors: F
authors: van Engelenburg
authors: Marieke
authors: M
authors: van den Dobbelsteen
authors: Michael
authors: M
authors: Adler
authors: Mario
authors: M
authors: Amacker
authors: Lucia
authors: L
authors: Lopalco
authors: Morgane
authors: M
authors: Bomsel
authors: Anick
authors: A
authors: Chalifour
authors: Sylvain
authors: S
authors: Fleury
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000276:immunology; D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006262:Health; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007273:Injections, Intramuscular; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D057900:Transcytosis / Q000276:immunology; D014611:Vaccination; D022223:Vaccines, Subunit / Q000009:adverse effects* / Q000276:immunology; D022701:Virosomes / Q000276:immunology*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C534067:HIV-1 envelope protein gp41 (649-683); D010446:Peptide Fragments; D022223:Vaccines, Subunit; D022701:Virosomes