BACKGROUND: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. METHODS: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. RESULTS: Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72-73% by genotyping (66-73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58-88%. CONCLUSIONS: gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates.

Austrian Agency for Health and Food Safety Institute for Medical Microbiology and Hygiene Graz Austria

Centers for Disease Control and Prevention Atlanta GA USA

Department of Infectious Parasitic and Immune mediated Diseases Istituto Superiore di Sanità Rome Italy

GSK Rockville USA

GSK Siena Italy

Institut Pasteur Paris France

Instituto Adolfo Lutz São Paulo Brazil

Irish Meningitis and Sepsis Reference Laboratory Dublin Ireland

Meningococcal Reference Unit Public Health England Manchester Royal Infirmary Manchester UK

National Centre for Microbiology Institute of Health Carlos 3 Madrid Spain

National Institute for Health and Welfare Helsinki Finland

National Institute of Health Dr Ricardo Jorge Lisbon Portugal

National Institute of Public Health Prague Czech Republic

National Medicines Institute Warsaw Poland

National Meningitis Reference Laboratory National School of Public Health Athens Greece

Norwegian Institute of Public Health Oslo Norway

Queensland Paediatric Infectious Diseases Laboratory Children's Health Research Centre University of Queensland Lady Cilento Children's Hospital South Brisbane Queensland Australia

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