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Infection and Immunity, January 2004, p. 345-351, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.345-351.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Vaccination with Attenuated Neisseria meningitidis Strains Protects against Challenge with Live Meningococci

Yanwen Li,¹ Yao-hui Sun,^1, Cathy Ison,² Myron M. Levine,³ and Christoph M. Tang^1*

Centre for Molecular Microbiology and Infection,¹ Department of Infectious Diseases and Microbiology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom,² Center for Vaccine Development, Baltimore, Maryland 21072³

Received 22 August 2003/ Returned for modification 25 September 2003/ Accepted 29 September 2003

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 (MC58sia rfaF) and YH103 (MC58sia metH). 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.

Editor: D. L. Burns

Present address: Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, College Station, Tex.

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