Genetic Distribution of Noncapsular Meningococcal Group B Vaccine Antigens in Neisseria lactamica

Abstract

bThe poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp), Neisseria adhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (Neisseria meningitidis); however, many subcapsular antigens are shared with nonpathogenic members of the genus Neisseria that also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal, Neisseria lactamica. All the isolates possessed nhba but were devoid of fhbp and nadA. The nhba alleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented.

Prevalence, sequence type, and quinolone resistance of Neisseria lactamica carried in children younger than 15 years in Shanghai, China

“…The low-level resistance (MIC, 0.06-0.5 μg/ml) was initiated with single amino acid mutations in GyrA including T91I, D95N, and D95Y. Then, based on T91I in GyrA, a second (19), N. mucosa (16), N. polysaccharea (15), N. cinerea (12), N. musculi (8), N. bergeri (5), N. bacilliformis (4), N. elongata (4), N. oralis (4), N. animalis (1), N. canis (1), N. dentiae (1), N. shayeganii (1), N. wadsworthii (1), and N. weaveri (1) genomes recorded in the Neisseria PubMLST database were employed. Each gyrA allele is normally shown as: gyrA _ gyrA allele_mutation_species_total number of isolates, and "Shanghai" is added following "species" when alleles were identified in this study, and these are indicated with a black triangle.…”

Genotypic Analysis of Meningococcal Factor H-Binding Protein from Non-Culture Clinical Specimens

“…Conservation of the primer site sequences in a related species could be indicative of functional constraint of the peptides for which they code and would increase confidence in the longevity of the primers. Recent work has confirmed that N. lactamica do not possess fHbp , and that the allele for NLA18150 (a putative opacity protein) can be found in its place at this locus flanked by genes common to both species [26], [28]. The PCR primers, targeting sequences within these flanking genes, should however produce an amplicon if the binding sites are conserved.…”

Virulence genes and previously unexplored gene clusters in four commensal Neisseria spp. isolated from the human throat expand the neisserial gene repertoire

“…In N. meningitidis, nadA assembles at the cell surface and promotes tight adherence followed by invasion of host epithelial cells [107]. Previous investigations into N. lactamica found no CDSs with homology to nadA or Bexsero target fHbp [108], both of which are found in these commensal isolates (Table 3). This analysis demonstrates additional reservoirs for antigenic variant alleles of NadA and Fhbp not represented in the vaccine that may allow N. meningitidis to escape vaccine-mediated control via HGT from commensal Neisseria spp.…”