Predicting the Susceptibility of Meningococcal Serogroup B Isolates to Bactericidal Antibodies Elicited by Bivalent rLP2086, a Novel Prophylactic Vaccine
Lisa K. McNeil,
Robert G. K. Donald,
Alexey Gribenko,
Roger French,
Nathaniel Lambert,
Shannon L. Harris,
Thomas R. Jones,
Sheng Li,
Gary Zlotnick,
Ulrich Vogel,
Heike Claus,
Raquel Abad,
Julio A. Vazquez,
Ray Borrow,
Jamie Findlow,
Muhamed-Kheir Taha,
Ala-Eddine Deghmane,
Dominique A. Caugant,
Paula Kriz,
Martin Musilek,
Xin Wang,
Jeni Vuong,
Leonard W. Mayer,
Michael W. Pride,
Kathrin U. Jansen,
Annaliesa S. Anderson
Affiliations
Lisa K. McNeil
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Robert G. K. Donald
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Alexey Gribenko
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Roger French
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Nathaniel Lambert
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Shannon L. Harris
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Thomas R. Jones
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Sheng Li
Department of Medicine, University of California, San Diego, California, USA
Gary Zlotnick
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Ulrich Vogel
Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany
Heike Claus
Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany
Raquel Abad
Reference and Research Laboratory for Vaccine Preventable Bacterial Diseases, Institute of Health Carlos III, Majadahonda, Spain
Julio A. Vazquez
Reference and Research Laboratory for Vaccine Preventable Bacterial Diseases, Institute of Health Carlos III, Majadahonda, Spain
Ray Borrow
Public Health England, Manchester Royal Infirmary, Manchester, United Kingdom
Jamie Findlow
Public Health England, Manchester Royal Infirmary, Manchester, United Kingdom
Muhamed-Kheir Taha
Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France
Ala-Eddine Deghmane
Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France
Dominique A. Caugant
Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Oslo, Norway
Paula Kriz
National Institute of Public Health, Prague, Czech Republic
Martin Musilek
National Institute of Public Health, Prague, Czech Republic
Xin Wang
Meningitis and Vaccine Preventable Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Jeni Vuong
Meningitis and Vaccine Preventable Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Leonard W. Mayer
Meningitis and Vaccine Preventable Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Michael W. Pride
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Kathrin U. Jansen
Pfizer Vaccine Research and Development, Pearl River, New York, USA
Annaliesa S. Anderson
Pfizer Vaccine Research and Development, Pearl River, New York, USA
ABSTRACT 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.