Abstract
ABSTRACTBivalent rLP2086 (Trumenba), a vaccine for prevention of Neisseria meningitidis serogroup B (NmB) disease, was licensed for use in adolescents and young adults after it was demonstrated that it elicits antibodies that initiate complement-mediated killing of invasive NmB isolates in a serum bactericidal assay with human complement (hSBA). The vaccine consists of two factor H binding proteins (fHBPs) representing divergent subfamilies to ensure broad coverage. Although it is the surrogate of efficacy, an hSBA is not suitable for testing large numbers of strains in local laboratories. Previously, an association between the in vitro fHBP surface expression level and the susceptibility of NmB isolates to killing was observed. Therefore, a flow cytometric meningococcal antigen surface expression (MEASURE) assay was developed and validated by using an antibody that binds to all fHBP variants from both fHBP subfamilies and accurately quantitates the level of fHBP expressed on the cell surface of NmB isolates with mean fluorescence intensity as the readout. Two collections of invasive NmB isolates (n = 1,814, n = 109) were evaluated in the assay, with the smaller set also tested in hSBAs using individual and pooled human serum samples from young adults vaccinated with bivalent rLP2086. From these data, an analysis based on fHBP variant prevalence in the larger 1,814-isolate set showed that >91% of all meningococcal serogroup B isolates expressed sufficient levels of fHBP to be susceptible to bactericidal killing by vaccine-induced antibodies.
Highlights
Bivalent rLP2086 (Trumenba), a vaccine for prevention of Neisseria meningitidis serogroup B (NmB) disease, was licensed for use in adolescents and young adults after it was demonstrated that it elicits antibodies that initiate complementmediated killing of invasive N. meningitidis serogroup B (NmB) isolates in a serum bactericidal assay with human complement
To further investigate the relationship between the total bacterial cell expression of factor H binding proteins (fHBPs) and the amount of fHBP localized on the bacterial surface, 38 isolates expressing one of nine different fHBP variants from both subfamilies A and B were tested by the meningococcal antigen surface expression (MEASURE) assay and fluorescent Western immunoblotting of cell lysates using polyclonal bivalent A and B rabbit serum samples
While fHBP expression cannot be directly measured in vivo, patients recovering from NmB infections develop anti-fHBP antibodies during convalescence [32]
Summary
Bivalent rLP2086 (Trumenba), a vaccine for prevention of Neisseria meningitidis serogroup B (NmB) disease, was licensed for use in adolescents and young adults after it was demonstrated that it elicits antibodies that initiate complementmediated killing of invasive NmB isolates in a serum bactericidal assay with human complement (hSBA). Two collections of invasive NmB isolates (n ϭ 1,814, n ϭ 109) were evaluated in the assay, with the smaller set tested in hSBAs using individual and pooled human serum samples from young adults vaccinated with bivalent rLP2086 From these data, an analysis based on fHBP variant prevalence in the larger 1,814-isolate set showed that Ͼ91% of all meningococcal serogroup B isolates expressed sufficient levels of fHBP to be susceptible to bactericidal killing by vaccine-induced antibodies. Licensure was achieved after it was demonstrated that the vaccines generated antibodies that could kill representative diseasecausing NmB isolates in a serum bactericidal assay with human complement (hSBA) [17,18,19,20]
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