title: Vaccine potential of the Neisseria meningitidis 2086 lipoprotein.
abstract: A novel antigen that induces cross-reactive bactericidal antibodies against a number of Neisseria meningitidis strains is described. This antigen, a approximately 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.
authors.affiliation: Wyeth Vaccines Research, Pearl River, New York 10965, USA.
authors.forename: Leah D
authors.initials: LD
authors.lastname: Fletcher
authors.forename: Liesel
authors.initials: L
authors.lastname: Bernfield
authors.forename: Vicki
authors.initials: V
authors.lastname: Barniak
authors.forename: John E
authors.initials: JE
authors.lastname: Farley
authors.forename: Alan
authors.initials: A
authors.lastname: Howell
authors.forename: Melissa
authors.initials: M
authors.lastname: Knauf
authors.forename: Peggy
authors.initials: P
authors.lastname: Ooi
authors.forename: Robert P
authors.initials: RP
authors.lastname: Smith
authors.forename: Paige
authors.initials: P
authors.lastname: Weise
authors.forename: Mike
authors.initials: M
authors.lastname: Wetherell
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xie
authors.forename: Robert
authors.initials: R
authors.lastname: Zagursky
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Gary W
authors.initials: GW
authors.lastname: Zlotnick
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007114:Immunization; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009343:Neisseria / Q000145:classification / Q000276:immunology; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008074:Lipoproteins; D022401:Meningococcal Vaccines; D011994:Recombinant Proteins; C484699:factor H-binding protein, Neisseria meningitidis