Vaccination with attenuated Neisseria meningitidis strains protects against challenge with live Meningococci.
Meningococcal disease is a life-threatening infection caused by Neisseria meningitidis. Currently, there are no vaccines to prevent infection with serogroup B N. meningitidis strains, the leading cause of meningococcal meningitis in Europe and North America. Here we describe the construction and characterization of two attenuated serogroup B N. meningitidis strains, YH102 (MC58deltasia deltarfaF) and YH103 (MC58deltasia deltametH). Both strains are markedly attenuated in their capacity to cause bacteremia in rodent models and have a reduced ability to survive in a human whole-blood assay. Immunization of adult mice with these strains leads to the development of bactericidal antibodies and confers sterilizing protection against challenge with homologous live bacteria. Furthermore, we show that the strains confer protection against infection by other serogroups. Use of the attenuated strains in animals with gene knockouts or after depletion of immunological effectors could be used to define the basis of protection, and human volunteer studies could be undertaken to examine the immune response following exposure to this important human pathogen.
Li
Yanwen
Y
Centre for Molecular Microbiology and Infection, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom.
Sun
Yao-hui
YH
Ison
Cathy
C
Levine
Myron M
MM
Tang
Christoph M
CM
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001770:Blood Bactericidal Activity; D006801:Humans; D008589:Meningococcal Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000276:immunology
D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines; D014613:Vaccines, Attenuated