Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/9138
Predicting the Susceptibility of Meningococcal Serogroup B Isolates to Bactericidal Antibodies Elicited by Bivalent rLP2086, a Novel Prophylactic Vaccine
McNeil, Lisa K | Donald, Robert G K | Gribenko, Alexey | French, Roger | Lambert, Nathaniel | Harris, Shannon L | Jones, Thomas R | Li, Sheng | Zlotnick, Gary | Vogel, Ulrich | Claus, Heike | Abad, Raquel ISCIII | Vazquez-Moreno, Julio Alberto ISCIII | Borrow, Ray | Findlow, Jamie | Taha, Muhamed-Kheir | Deghmane, Ala-Eddine | Caugant, Dominique A | Kriz, Paula | Musilek, Martin | Wang, Xin | Vuong, Jeni | Mayer, Leonard W | Pride, Michael W | Jansen, Kathrin U | Anderson, Annaliesa S
mBio. 2018 Mar 13;9(2). pii: e00036-18.
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.
Neisseria meningitidis serogroup B | factor H binding protein | flow cytometry | meningococcal antigen surface expression (MEASURE) assay | vaccine
Anti-Bacterial Agents | Antibodies, Bacterial | Antigens, Bacterial | Bacterial Proteins | Blood Bactericidal Activity | Flow Cytometry | Humans | Meningococcal Vaccines | Microbial Viability | Neisseria meningitidis, Serogroup B
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