title: Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease.
abstract: Factor H binding proteins (fHBP), are bacterial surface proteins currently undergoing human clinical trials as candidate serogroup B Neisseria meningitidis (MnB) vaccines. fHBP protein sequences segregate into two distinct subfamilies, designated A and B. Here, we report the specificity and vaccine potential of mono- or bivalent fHBP-containing vaccines. A bivalent fHBP vaccine composed of a member of each subfamily elicited substantially broader bactericidal activity against MnB strains expressing heterologous fHBP than did either of the monovalent vaccines. Bivalent rabbit immune sera tested in serum bactericidal antibody assays (SBAs) against a diverse panel of MnB clinical isolates killed 87 of the 100 isolates. Bivalent human immune sera killed 36 of 45 MnB isolates tested in SBAs. Factors such as fHBP protein variant, PorA subtype, or MLST were not predictive of whether the MnB strain could be killed by rabbit or human immune sera. Instead, the best predictor for killing in the SBA was the level of in vitro surface expression of fHBP. The bivalent fHBP vaccine candidate induced immune sera that killed MnB isolates representing the major MLST complexes, prevalent PorA subtypes, and fHBP variants that span the breadth of the fHBP phylogenetic tree. Importantly, epidemiologically prevalent fHBP variants from both subfamilies were killed.
authors.affiliation: Pfizer Vaccine Research, 401N. Middletown Rd., Pearl River, NY 10965, USA.
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Jiang
authors.forename: Susan K
authors.initials: SK
authors.lastname: Hoiseth
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Harris
authors.forename: Lisa K
authors.initials: LK
authors.lastname: McNeil
authors.forename: Duzhang
authors.initials: D
authors.lastname: Zhu
authors.forename: Cuiwen
authors.initials: C
authors.lastname: Tan
authors.forename: Adrienne A
authors.initials: AA
authors.lastname: Scott
authors.forename: Kristin
authors.initials: K
authors.lastname: Alexander
authors.forename: Kathryn
authors.initials: K
authors.lastname: Mason
authors.forename: Lynn
authors.initials: L
authors.lastname: Miller
authors.forename: Ida
authors.initials: I
authors.lastname: DaSilva
authors.forename: Michelle
authors.initials: M
authors.lastname: Mack
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhao
authors.forename: Michael W
authors.initials: MW
authors.lastname: Pride
authors.forename: Lubomira
authors.initials: L
authors.lastname: Andrew
authors.forename: Ellen
authors.initials: E
authors.lastname: Murphy
authors.forename: Michael
authors.initials: M
authors.lastname: Hagen
authors.forename: Roger
authors.initials: R
authors.lastname: French
authors.forename: Ashoni
authors.initials: A
authors.lastname: Arora
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Jones
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Gary W
authors.initials: GW
authors.lastname: Zlotnick
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D015610:Serum Bactericidal Test; D013045:Species Specificity
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; D011994:Recombinant Proteins; C484699:factor H-binding protein, Neisseria meningitidis