Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process

• Published in: Vaccine 2010-07, Vol.28 (30), p.4810-4816
• Main Authors: van de Waterbeemd, Bas, Streefland, Mathieu, van der Ley, Peter, Zomer, Bert, van Dijken, Harry, Martens, Dirk, Wijffels, René, van der Pol, Leo
• Format: Article
• Language: English
• Subjects: Aggregation; Allergy and Immunology; Animals; antibody-responses; Applied microbiology; b meningococcal vaccine; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - immunology; Bacterial Outer Membrane Proteins - isolation & purification; bactericidal activity; Bacteriology; binding protein; Biological and medical sciences; Cross-protection; escherichia-coli; Fundamental and applied biological sciences. Psychology; Genetic Engineering; Immune response; Immunogenicity; lipopolysaccharide-deficient mutant; Lipopolysaccharides; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - toxicity; lpxL1; membrane vesicle vaccine; Membrane vesicles; Meningitis; Meningococcal Infections - immunology; Meningococcal Vaccines - chemistry; Meningococcal Vaccines - immunology; Meningococcal Vaccines - toxicity; Mice; Microbiology; Miscellaneous; Mutation; Neisseria meningitidis; Neisseria meningitidis, Serogroup B - genetics; Neisseria meningitidis, Serogroup B - immunology; OMV; Outer membranes; Point mutation; Purification; Purification process; rmpM; serogroup-b; Toxicity; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vesicles; Yield
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.04.082

Abstract The use of detergent-extracted outer membrane vesicles (OMVs) is an established approach for development of a multivalent PorA vaccine against N. meningitidis serogroup B. Selective removal of lipopolysaccharide (LPS) decreases toxicity, but promotes aggregation and narrows the immune response. Detergent-free OMV vaccines retain all LPS, which preserves the native vesicle structure, but result in high toxicity and lower yield. The present study assessed the effects of gene mutations that attenuated LPS toxicity ( lpxL1 ) or improved OMV yield ( rmpM ) in combination with the available OMV purification processes. The results substantiate that OMVs from a strain with both mutations, produced with a detergent-free process provide better vaccine characteristics than the traditional detergent-based approach. With comparable toxicity and yield, no aggregation and cross-protection against other PorA subtypes, these OMV vaccines are potentially safe and effective for parenteral use in humans.