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

Charlene M C Rodrigues,J Claire Cameron,Martin C J Maiden,Keith A Jolley,Andrew Smith,Ian M Feavers,Daniel J Diekema

doi:10.1128/jcm.02161-20

Abstract

As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole-genome sequence data by nonspecialists 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 and 2014. These vaccines have different components and different levels of 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 synthesized 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, the MenDeVAR Index 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 programs. The MenDeVAR Index has been developed in consultation with, but independently of, both the 4CMenB (Bexsero; GSK) and rLP2086 (Trumenba; Pfizer, Inc.) vaccine manufacturers.

Highlights

As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole-genome sequence data by nonspecialists becomes essential
Novel peptide variants are curated in real time after submission to PubMLST; these curated databases form the basis of the MenDeVAR Index
With the exception of two studies [34, 40] that used a positive bactericidal threshold (PBT) for factor H binding protein (fHbp) of 0.012, all other antigen relative potency (RP) were assessed against PBTs of 0.021 for fHbp, 0.294 for NHBA, and 0.009 for NadA [18]

Summary

Introduction

As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole-genome sequence data by nonspecialists becomes essential. 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 antibodydependent bactericidal killing. Using whole-genome sequences or individual gene sequences obtained from IMD isolates or clinical specimens, the MenDeVAR Index provides rapid evidence-based information on the presence and possible immunological cross-reactivity of different meningococcal vaccine antigen variants. Prevention of IMD is possible by immunization, delivered either by routine programs or in response to clusters or outbreaks When they occur, such outbreaks are a public health priority, requiring the rapid identification of individuals at high risk from the meningococcal variant identified in the index case. The Bexsero antigen sequence typing (BAST) scheme was established to characterize and describe vaccine antigen variants, using data derived through WGS or sequencing of individual genes [16]

Methods

Results

Conclusion