Phase I study of a Neisseria meningitidis liposomal vaccine containing purified outer membrane proteins and detoxified lipooligosaccharide

Vaccine. 2012 Jan 17;30(4):712-21. doi: 10.1016/j.vaccine.2011.11.084. Epub 2011 Dec 3.

Abstract

Purified outer membrane proteins and purified deacylated lipooligosaccharide (dLOS) were formulated for use as a vaccine in three formulations for clinical use. The three vaccine formulations included (1) purified outer membrane proteins (OMPs) and L8-5 dLOS adsorbed to aluminum hydroxide; (2) purified OMPs and L8-5 dLOS incorporated into liposomes; and (3) purified OMPs and L7 dLOS incorporated into proteoliposomes. The vaccines were compared for immunogenicity and safety in a phase 1clinical study. Ten adult volunteers were vaccinated with each of the three vaccine formulations. Two 50 μg doses were given six weeks apart, and serum samples were obtained at 0, 2, 6, 8 and 14 weeks. Volunteers were evaluated for reactogenicity 30 min after vaccination and at days 1, 2, and 14 after each vaccination, and laboratory safety tests were done at 0, 2 and 6 weeks. Overall, the vaccines were well tolerated. Bactericidal assays against a homologous strain showed a four-fold or greater increase in titer in 6 of 7 volunteers in group one, 9 of 10 volunteers in group two, and 5 of 10 volunteers in group three. A quantitative enzyme linked immunosorbant assay showed increases in antibody against both OMPs and LOS antigens. The liposome formulation appeared to be particularly effective in presenting the dLOS as an antigen.

Publication types

  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adolescent
  • Adult
  • Aluminum Hydroxide / administration & dosage
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Outer Membrane Proteins / isolation & purification
  • Blood Bactericidal Activity
  • Female
  • Humans
  • Lipopolysaccharides / immunology*
  • Lipopolysaccharides / isolation & purification
  • Liposomes / administration & dosage*
  • Male
  • Meningococcal Vaccines / administration & dosage
  • Meningococcal Vaccines / adverse effects
  • Meningococcal Vaccines / immunology*
  • Middle Aged
  • Neisseria meningitidis / immunology*
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Bacterial Outer Membrane Proteins
  • Lipopolysaccharides
  • Liposomes
  • Meningococcal Vaccines
  • lipid-linked oligosaccharides
  • Aluminum Hydroxide