Preclinical safety and immunogenicity evaluation of a nonavalent PorA native outer membrane vesicle vaccine against serogroup B meningococcal disease

Vaccine. 2013 Feb 4;31(7):1065-71. doi: 10.1016/j.vaccine.2012.12.031. Epub 2012 Dec 27.

Abstract

Background: An improved nonavalent PorA native outer membrane vesicle vaccine was developed with intrinsic adjuvating activity due to presence of less-toxic (lpxL1) LPS. In the present study, the safety and immunogenicity of this next-generation NonaMen vaccine were evaluated following repeated vaccination in rabbits and mice.

Methods: A repeated-dose toxicology study was performed in rabbits. Immunogenicity of next-generation NonaMen was evaluated by determining the serum bactericidal antibody (SBA) titers against meningococcal serogroup B strains containing several PorA subtypes. Release of the pro-inflammatory cytokine, interleukin-6 (IL-6), by the human monocytic cell line (MM6) was measured to estimate pyrogenic activity.

Results: No toxicologically relevant findings were noted in vaccinated rabbits receiving plain next-generation NonaMen. In agreement, next-generation NonaMen induced reduced amounts of the pro-inflammatory cytokine, IL-6, released by human monocyte cell line. In both rabbits and mice, next-generation NonaMen induced high SBA titers against all tested MenB strains regardless of whether or not aluminium phosphate adjuvant is used.

Conclusions: The data suggest that next-generation NonaMen is a safe vaccine with the potential to develop a broadly protective immune response and encourage the start of the first clinical studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Animals
  • Antigens, Bacterial / administration & dosage
  • Antigens, Bacterial / immunology*
  • Blood Bactericidal Activity
  • Female
  • Interleukin-6 / metabolism
  • Male
  • Meningococcal Vaccines / adverse effects*
  • Meningococcal Vaccines / immunology*
  • Mice
  • Microbial Viability
  • Monocytes / immunology
  • Neisseria meningitidis, Serogroup B / immunology*
  • Porins / administration & dosage*
  • Porins / adverse effects
  • Rabbits
  • Vaccination / adverse effects
  • Vaccination / methods

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Interleukin-6
  • Meningococcal Vaccines
  • Porins
  • porin protein, Neisseria