Preclinical safety and immunogenicity evaluation of a nonavalent PorA native outer membrane vesicle vaccine against serogroup B meningococcal disease |
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Authors: | Patricia Kaaijk Ineke van Straaten Bas van de Waterbeemd Elmieke PJ Boot Lonneke MAR Levels Harry H van Dijken Germie PJM van den Dobbelsteen |
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Institution: | 1. Unit Vaccinology, Centre for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands;2. Netherlands Vaccine Institute, Quality Control Department, Bilthoven, The Netherlands |
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Abstract: | BackgroundAn 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.MethodsA 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.ResultsNo 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.ConclusionsThe 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. |
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Keywords: | MenB Neisseria meningitidis serogroup B OMV outer membrane vesicles DOMV detergent OMV NOMV native OMV PorA outer membrane porin A protein LPS lipopolysaccharide MAT monocyte activation test SBA serum bactericidal antibody LAL limulus amebocyte lysate DTwcP-IPV diphtheria toxoid tetanus toxoid whole cell pertussis inactivated poliomyelitis virus type 1 2 3 |
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