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Infection and Immunity, April 2004, p. 2088-2100, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2088-2100.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Vaccine Potential of the Neisseria meningitidis 2086 Lipoprotein

Leah D. Fletcher, Liesel Bernfield, Vicki Barniak, John E. Farley, Alan Howell, Melissa Knauf, Peggy Ooi, Robert P. Smith, Paige Weise, Mike Wetherell, Xiaoling Xie, Robert Zagursky, Ying Zhang, and Gary W. Zlotnick*

Wyeth Vaccines Research, Pearl River, New York 10965

Received 22 July 2003/ Returned for modification 5 September 2003/ Accepted 18 December 2003

A novel antigen that induces cross-reactive bactericidal antibodies against a number of Neisseria meningitidis strains is described. This antigen, a ~28-kDa lipoprotein called LP2086, was first observed within a complex mixture of soluble outer membrane proteins (sOMPs) following a series of fractionation, protein purification, and proteomics steps. Approximately 95 different neisserial isolates tested positive by Western blotting and PCR screening methods for the presence of the protein and the gene encoding LP2086. The strains tested included isolates of N. meningitidis serogroups A, B, C, W135, and Y, Neisseria gonorrhoeae, and Neisseria lactamica. To better understand the microheterogeneity of this protein, the 2086 genes from 63 neisserial isolates were sequenced. Two different subfamilies of LP2086 were identified based on deduced amino acid sequence homology. A high degree of amino acid sequence similarity exists within each 2086 subfamily. The highest degree of genetic diversity was seen between the two subfamilies which share approximately 60 to 75% homology at the nucleic acid level. Flow cytometry (fluorescence-activated cell sorting) analyses and electron microscopy indicated that the LP2086 is localized on the outer surface of N. meningitidis. Antiserum produced against a single protein variant was capable of eliciting bactericidal activity against strains expressing different serosubtype antigens. Combining one recombinant lipidated 2086 (rLP2086) variant from each subfamily with two rPorA variants elicited bactericidal activity against all strains tested. The rLP2086 family of antigens are candidates worthy of further vaccine development.

* Corresponding author. Mailing address: Wyeth Vaccines Discovery Research, Bldg. 205, Rm. 227, 401 N. Middletown Rd., Pearl River, NY 10965. Phone: (845) 602-3015. Fax: (845) 602-4350. E-mail: zlotnig{at}wyeth.com.

Editor: J. N. Weiser

Infection and Immunity, April 2004, p. 2088-2100, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2088-2100.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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