Immunogenicity of a meningococcal native outer membrane vesicle vaccine with attenuated endotoxin and over-expressed factor H binding protein in infant rhesus monkeys
| Autor: | Oliver Koeberling, George Santos, John J. Donnelly, Mildred Ugozzoli, Dan M. Granoff, Anja Seubert, Annalisa Colaprico |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Bactericidal Activity
medicine.medical_treatment Immunization Secondary Meningococcal Vaccines Meningococcal vaccine Vaccines Attenuated Article Microbiology Bacterial Proteins Antigen Cell-Derived Microparticles medicine Animals Antigens Bacterial General Veterinary General Immunology and Microbiology biology Immunogenicity Vaccination Public Health Environmental and Occupational Health Antibodies Bacterial Macaca mulatta Virology Endotoxins Infectious Diseases Leukocytes Mononuclear biology.protein Cytokines Molecular Medicine Antibody Bacterial outer membrane Adjuvant |
| Zdroj: | Vaccine. 29:4728-4734 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2011.04.095 |
| Popis: | We previously investigated immunogenicity of meningococcal native outer membrane vesicle (NOMV) vaccines prepared from recombinant strains with attenuated endotoxin (ΔLpxL1) and over-expressed factor H binding protein (fHbp) in a mouse model. The vaccines elicited broad serum bactericidal antibody responses. While human toll-like receptor 4 (TLR-4) is mainly stimulated by wildtype meningococcal endotoxin, mouse TLR-4 is stimulated by both the wildtype and mutant endotoxin. An adjuvant effect in mice of the mutant endotoxin would be expected to be much less in humans, and may have contributed to the broad mouse bactericidal responses. Here we show that as previously reported for humans, rhesus primate peripheral blood mononuclear cells incubated with a NOMV vaccine from ΔLpxL1 recombinant strains had lower proinflammatory cytokine responses than with a control wildtype NOMV vaccine. The cytokine responses to the mutant vaccine were similar to those elicited by a detergent-treated, wildtype outer membrane vesicle vaccine that had been safely administered to humans. Monkeys (N=4) were immunized beginning at ages 2 to 3 months with three doses of a NOMV vaccine prepared from ΔLpxL1 recombinant strains with over-expressed fHbp in the variant 1 and 2 groups. The mutant NOMV vaccine elicited serum bactericidal titers ≥1:4 against all 10 genetically diverse strains tested, including 9 with heterologous PorA to those in the vaccine. Negative-control animals had serum bactericidal titers |
| Databáze: | OpenAIRE |
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