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 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.IMPORTANCE Bivalent rLP2086 (Trumenba) vaccine, composed of two factor H binding proteins (fHBPs), was recently licensed for the prevention of N. meningitidis serogroup B (NmB) disease in individuals 10 to 25 years old in the United States. This study evaluated a large collection of NmB isolates from the United States and Europe by using a flow cytometric MEASURE assay to quantitate the surface expression of the vaccine antigen fHBP. We find that expression levels and the proportion of strains above the level associated with susceptibility in an hSBA are generally consistent across these geographic regions. Thus, the assay can be used to predict which NmB isolates are susceptible to killing in the hSBA and therefore is able to demonstrate an fHBP vaccine-induced bactericidal response. This work significantly advances our understanding of the potential for bivalent rLP2086 to provide broad coverage against diverse invasive-disease-causing NmB isolates.

• Klíčová slova
• Neisseria meningitidis serogroup B, factor H binding protein, flow cytometry, meningococcal antigen surface expression (MEASURE) assay, vaccine,
• MeSH
• antibakteriální látky farmakologie   MeSH
• antigeny bakteriální analýza   MeSH
• bakteriální proteiny analýza   MeSH
• baktericidní aktivita krve MeSH
• lidé MeSH
• meningokokové vakcíny imunologie   MeSH
• mikrobiální viabilita účinky léků   MeSH
• Neisseria meningitidis séroskupiny B chemie   účinky léků   izolace a purifikace   fyziologie   MeSH
• protilátky bakteriální farmakologie   MeSH
• průtoková cytometrie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antigeny bakteriální MeSH
• bakteriální proteiny MeSH
• factor H-binding protein, Neisseria meningitidis MeSH Prohlížeč
• meningokokové vakcíny MeSH
• protilátky bakteriální MeSH

The effect of a 20-min exposure to antibody-quantum dot (Ab-QD) conjugates on colony counts of Escherichia coli was assessed by the spread-plate method and compared with exposure to unconjugated QDs having only amine or carboxyl groups on their surfaces. Under these conditions, Ab-QD conjugates generally exhibited >90% reduction in colony-forming units as compared to untreated E. coli and E. coli treated with unconjugated QDs after incubation for as long as 41 h. The antibacterial effect of Ab-QD conjugates vs. unconjugated QDs on Salmonella enterica subsp. enterica serovar Typhimurium was also assessed by means of a disk-diffusion technique which demonstrated greater growth inhibition (approximately 3 mm greater) by Ab-QD conjugate-impregnated disks than by unconjugated-QD-only-impregnated disks at a 10-microg disk load. At a 25-microg disk load, both treatment groups exhibited nearly equal growth inhibition.

• MeSH
• antibakteriální látky farmakologie   MeSH
• biotechnologie metody   MeSH
• Escherichia coli účinky léků   růst a vývoj   MeSH
• imunokonjugáty MeSH
• kvantové tečky * MeSH
• mikrobiální testy citlivosti metody   MeSH
• monoklonální protilátky * chemie   imunologie   farmakologie   MeSH
• počet mikrobiálních kolonií MeSH
• protilátky bakteriální * chemie   imunologie   farmakologie   MeSH
• Salmonella typhimurium účinky léků   růst a vývoj   MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• antibakteriální látky MeSH
• imunokonjugáty MeSH
• monoklonální protilátky * MeSH
• protilátky bakteriální * MeSH