Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index: a Rapid and Accessible Tool that Exploits Genomic Data in Public Health and Clinical Microbiology Applications

Abstract

As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole genome sequence data by non-specialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD), since their licensure in 2013/14. These vaccines have different components and different coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate including: (i) the presence of particular vaccine antigen variants; (ii) the expression of vaccine antigens; and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing. To obtain this information requires a multitude of laboratory assays, impractical in real-time clinical settings, where the information is most urgently needed. To facilitate assessment for public health and clinical purposes, we synthesised genomic and experimental data from published sources to develop and implement the 'Meningococcal Deduced Vaccine Antigen Reactivity' (MenDeVAR) Index, which is publicly-available on PubMLST (https://pubmlst.org). Using whole genome sequences or individual gene sequences obtained from IMD isolates or clinical specimens, MenDeVAR provides rapid evidence-based information on the presence and possible immunological cross-reactivity of different meningococcal vaccine antigen variants. The MenDeVAR Index enables practitioners who are not genomics specialists to assess the likely reactivity of vaccines for individual cases, outbreak management, or the assessment of public health vaccine programmes. MenDeVAR has been developed in consultation with, but independently of, both vaccine manufacturers.

High coverage of diverse invasive meningococcal serogroup B strains by the 4-component vaccine 4CMenB in Australia, 2007–2011: Concordant predictions between MATS and genetic MATS

“…The intrinsic value of gMATS resides also in its ability to predict coverage for PCR-confirmed IMD cases as well, 15 which represent an increasingly important proportion of reported cases worldwide. In Australia, around 22% of IMD cases were diagnosed using PCR alone in 2018, 24 , 25 emphasizing the role of genomic approaches such as gMATS, BAST and the recently-developed Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVar) 38 in the assessment of vaccines against MenB. This study represents an additional evidence on the high concordance between MATS and gMATS predictions, as already shown on strain panels deriving from 13 countries worldwide 15 and further supports the added value of gMATS for the prediction of 4CMenB coverage over time and across geographies.…”