TY - JOUR
T1 - Prevalence of factor H-binding protein variants and NadA among meningococcal group B isolates from the United States
T2 - Implications for the development of a multicomponent group B vaccine
AU - Beernink, Peter T.
AU - Welsch, Jo Anne
AU - Harrison, Lee H.
AU - Leipus, Arunas
AU - Kaplan, Sheldon L.
AU - Granoff, Dan M.
N1 - Funding Information:
Financial support: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH; grants R01 AI46464, R01 AI58122, and R21 AI61533 to D.M.G. and Research Career Award K24 AI52788 to L.H.H.); Sanofi Pasteur (grant to S.L.K. to support the multicenter surveillance study). The investigation was conducted in a facility constructed with support from the National Center for Research Resources, NIH (Research Facilities Improvement Program grant CO6 RR16226). a P.T.B. and J.A.W. contributed equally to this work.
Funding Information:
Potential conflicts of interest: D.M.G.’s laboratory at Children’s Hospital Oakland Research Institute has research grants from Novartis Vaccines and Diagnostics and from Sanofi Pasteur. D.M.G. also holds a paid consultancy from Novartis. L.H.H. receives research grant support from Sanofi Pasteur and serves as a paid consultant to Sanofi Pasteur, GlaxoSmithKline, and Novartis; he also receives speaking honoraria from Sanofi Pasteur. All other authors declare no conflicts of interest.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - Background. Two promising recombinant meningococcal protein vaccines are in development. One contains factor H-binding protein (fHBP) variants (v.) 1 and 2, whereas the other contains v.1 and 4 other antigens discovered by genome mining (5 component [5C]). Antibodies against fHBP are bactericidal against strains within a variant group. There are limited data on the prevalence of strains expressing different fHBP variants in the United States. Methods. A total of 143 group B isolates from patients hospitalized in the United States were tested for fHBP variant by quantitative polymerase chain reaction, for reactivity with 6 anti-fHBP monoclonal antibodies (MAb) by dot immunoblotting, and for susceptibility to bactericidal activity of mouse antisera. Results. fHBP v.1 isolates predominated in California (83%), whereas isolates expressing v.1 (53%) or v.2 (42%) were common in 9 other states. Isolates representative of 5 anti-fHBP MAb-binding phenotypes (70% of isolates) were highly susceptible to anti-fHBP v.1 or v.2 bactericidal activity, whereas 3 phenotypes were ∼50% susceptible. Collectively, antibodies against the fHBP v.1 and v.2 vaccine and the 5C vaccine killed 76% and 83% of isolates, respectively. Conclusions. Susceptibility to bactericidal activity can be predicted, in part, on the basis of fHBP phenotypes. Both vaccines have the potential to prevent most group B disease in the United States.
AB - Background. Two promising recombinant meningococcal protein vaccines are in development. One contains factor H-binding protein (fHBP) variants (v.) 1 and 2, whereas the other contains v.1 and 4 other antigens discovered by genome mining (5 component [5C]). Antibodies against fHBP are bactericidal against strains within a variant group. There are limited data on the prevalence of strains expressing different fHBP variants in the United States. Methods. A total of 143 group B isolates from patients hospitalized in the United States were tested for fHBP variant by quantitative polymerase chain reaction, for reactivity with 6 anti-fHBP monoclonal antibodies (MAb) by dot immunoblotting, and for susceptibility to bactericidal activity of mouse antisera. Results. fHBP v.1 isolates predominated in California (83%), whereas isolates expressing v.1 (53%) or v.2 (42%) were common in 9 other states. Isolates representative of 5 anti-fHBP MAb-binding phenotypes (70% of isolates) were highly susceptible to anti-fHBP v.1 or v.2 bactericidal activity, whereas 3 phenotypes were ∼50% susceptible. Collectively, antibodies against the fHBP v.1 and v.2 vaccine and the 5C vaccine killed 76% and 83% of isolates, respectively. Conclusions. Susceptibility to bactericidal activity can be predicted, in part, on the basis of fHBP phenotypes. Both vaccines have the potential to prevent most group B disease in the United States.
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U2 - 10.1086/514821
DO - 10.1086/514821
M3 - Article
C2 - 17436227
AN - SCOPUS:34248166509
SN - 0022-1899
VL - 195
SP - 1472
EP - 1479
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -