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Infection and Immunity, October 2005, p. 6838-6845, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6838-6845.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Evaluation of Recombinant Lipidated P2086 Protein as a Vaccine Candidate for Group B Neisseria meningitidis in a Murine Nasal Challenge Model

Duzhang Zhu,* Ying Zhang, Vicki Barniak, Liesel Bernfield, Alan Howell, and Gary Zlotnick

Wyeth Vaccines Research, Pearl River, New York 10965

Received 4 March 2005/ Returned for modification 15 April 2005/ Accepted 23 June 2005

Neisseria meningitidis is a major causative agent of bacterial meningitis in human beings, especially among young children (≤2 years of age). Prevention of group B meningococcal disease represents a particularly difficult challenge in vaccine development, due to the inadequate immune response elicited against type B capsular polysaccharide. We have established an adult mouse intranasal challenge model for group B N. meningitidis to evaluate potential vaccine candidates through active immunization. Swiss Webster mice were inoculated intranasally with meningococci, and bacteria were recovered from the noses for at least 3 days postchallenge. Iron dextran was required in the bacterial inoculum to ensure sufficient meningococcal recovery from nasal tissue postchallenge. This model has been utilized to evaluate the potential of a recombinant lipidated group B meningococcal outer membrane protein P2086 (rLP2086) as a vaccine candidate. In this study, mice were immunized subcutaneously with purified rLP2086 formulated with or without an attenuated cholera toxin as an adjuvant. The mice were then challenged intranasally with N. meningitidis strain H355 or M982, and the colonization of nasal tissue was determined by quantitative culture 24 h postchallenge. We demonstrated that immunization with rLP2086 significantly reduced nasal colonization of mice challenged with the two different strains of group B N. meningitidis. Mice immunized with rLP2086 produced a strong systemic immunoglobulin G response, and the serum antibodies were cross-reactive with heterologous strains of group B N. meningitidis. The antibodies have functional activity against heterologous N. meningitidis strain, as demonstrated via bactericidal and infant rat protection assays. These results suggest that rLP2086 is a potential vaccine candidate for group B N. meningitidis.

* Corresponding author. Mailing address: Wyeth Research, 401 N. Middletown Rd., Bldg. 180/214, Pearl River, NY 10965. Phone: (845) 602-3446. Fax: (845) 602-4941. E-mail: zhudz{at}wyeth.com.

Editor: J. N. Weiser

Infection and Immunity, October 2005, p. 6838-6845, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6838-6845.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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