Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease.
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.
Jiang
Han-Qing
HQ
Pfizer Vaccine Research, 401N. Middletown Rd., Pearl River, NY 10965, USA.
Hoiseth
Susan K
SK
Harris
Shannon L
SL
McNeil
Lisa K
LK
Zhu
Duzhang
D
Tan
Cuiwen
C
Scott
Adrienne A
AA
Alexander
Kristin
K
Mason
Kathryn
K
Miller
Lynn
L
DaSilva
Ida
I
Mack
Michelle
M
Zhao
Xiao-Juan
XJ
Pride
Michael W
MW
Andrew
Lubomira
L
Murphy
Ellen
E
Hagen
Michael
M
French
Roger
R
Arora
Ashoni
A
Jones
Thomas R
TR
Jansen
Kathrin U
KU
Zlotnick
Gary W
GW
Anderson
Annaliesa S
AS
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
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; D011994:Recombinant Proteins; C484699:factor H-binding protein, Neisseria meningitidis