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Infection and Immunity, December 2007, p. 5939-5946, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00846-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Agonists of Toll-Like Receptors 3, 4, 7, and 9 Are Candidates for Use as Adjuvants in an Outer Membrane Vaccine against Neisseria meningitidis Serogroup B{triangledown}

Floris Fransen,1,2* Claire J. Boog,1 Jos P. van Putten,2 and Peter van der Ley1

Laboratory for Vaccine Research, The Netherlands Vaccine Institute, Antonie van Leeuwenhoeklaan 11-13, 3720 AL Bilthoven, The Netherlands,1 Department of Infectious Diseases and Immunology, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands2

Received 20 June 2007/ Returned for modification 25 July 2007/ Accepted 18 September 2007

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 lipopolysaccharide (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 Toll-like receptor (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 immunoglobulin G (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.

* Corresponding author. Mailing address: Antonie van Leeuwenhoeklaan 11-13, 3720 AL Bilthoven, The Netherlands. Phone: 31 302743999. Fax: 31 302744429. E-mail: Floris.Fransen{at}nvi-vaccin.nl

{triangledown} Published ahead of print on 1 October 2007.

Editor: R. P. Morrison

Infection and Immunity, December 2007, p. 5939-5946, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00846-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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