title: Meningococcal vaccine antigen diversity in global databases.
abstract: The lack of an anti-capsular vaccine against serogroup B meningococcal disease has necessitated the exploration of alternative vaccine candidates, mostly proteins exhibiting varying degrees of antigenic variation. Analysis of variants of antigen-encoding genes is facilitated by publicly accessible online sequence repositories, such as the Neisseria PubMLST database and the associated Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL). We investigated six proposed meningococcal vaccine formulations by deducing the prevalence of their components in the isolates represented in these repositories. Despite high diversity, a limited number of antigenic variants of each of the vaccine antigens were prevalent, with strong associations of particular variant combinations with given serogroups and genotypes. In the MRF-MGL and globally, the highest levels of identical sequences were observed with multicomponent/multivariant vaccines. Our analyses further demonstrated that certain combinations of antigen variants were prevalent over periods of decades in widely differing locations, indicating that vaccine formulations containing a judicious choice of antigen variants have potential for long-term protection across geographic regions. The data further indicated that formulations with multiple variants would be especially relevant at times of low disease incidence, as relative diversity was higher. Continued surveillance is required to monitor the changing prevalence of these vaccine antigens.
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, United Kingdom.
authors.forename: Carina
authors.initials: C
authors.lastname: Brehony
authors.forename: Dorothea M
authors.initials: DM
authors.lastname: Hill
authors.forename: Jay
authors.initials: J
authors.lastname: Lucidarme
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Martin C
authors.initials: MC
authors.lastname: Maiden
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000276:immunology*; D008875:Middle Aged; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics*; D017422:Sequence Analysis, DNA; D065288:Serogroup; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines
keywords: Neisseria meningitidis; antigens; genomics; molecular epidemiology; multivalent; vaccine design