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Infect. Immun. doi:10.1128/IAI.00846-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Agonists of Toll-like receptor 3, 4, 7, and 9 are adjuvant candidates for use in an outer membrane vaccine against Neisseria meningitidis serogroup B

Laboratory for Vaccine Research, Netherlands Vaccine Institute (NVI), Antonie van Leeuwenhoeklaan 11-13, 3720 AL Bilthoven, The Netherlands; Department of Infectious Diseases and Immunology, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands

^* To whom correspondence should be addressed. Email: Floris.Fransen{at}nvi-vaccin.nl.

	Abstract

The bacterium Neisseria meningitidis is the causative agent of meningitis and sepsis. A generally effective vaccine against N. meningitidis serogroup B is not yet available, but outer membrane vesicle vaccines are in development. These vaccines contain LPS. The inclusion of N. meningitidis wild-type LPS in a vaccine is controversial because of its high toxicity. Therefore, the adjuvant activity of a panel of different TLR agonists in combination with LPS-deficient meningococcal outer membrane complexes was compared after immunization of mice. The results demonstrate that TLR3, TLR4, TLR7, and TLR9 agonists enhance immune responses against LPS-deficient outer membrane complexes. Their adjuvant activity was characterized by higher levels of antigen-specific IgG, IgG2a, and IgG2b, a higher IgG2a/IgG1 ratio, lower total IgE levels, and most importantly, higher serum bactericidal antibody titers compared to LPS-deficient outer membrane complexes alone.