Molecular characterization of invasive serogroup B Neisseria meningitidis isolates from Spain during 2015–2018: Evolution of the vaccine antigen factor H binding protein (FHbp)

ABSTRACTNeisseria meningitidisremains a leading cause of bacterial sepsis and meningitis. Complement is a key component of natural immunity against this important human pathogen, which has evolved multiple mechanisms to evade complement-mediated lysis. One approach adopted by the meningococcus is to recruit a human negative regulator of the complement system, factor H (fH), to its surface via a lipoprotein, factor H binding protein (fHbp). Additionally, fHbp is a key antigen in vaccines currently being evaluated in clinical trials. Here we characterize strains ofN. meningitidisfrom several distinct clonal complexes which do not express fHbp; all strains were recovered from patients with disseminated meningococcal disease. We demonstrate that these strains have either a frameshift mutation in thefHbpopen reading frame or have entirely lostfHbpand some flanking sequences. No fH binding was detected to other ligands among thefHbp-negative strains. The implications of these findings for meningococcal pathogenesis and prevention are discussed.

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Faculty Opinions recommendation of Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11884956.12990056 ◽

2011 ◽

Author(s):

Rino Rappuoli ◽

Davide Serruto

Keyword(s):

Neisseria Meningitidis ◽

Virulence Factor ◽

Binding Protein ◽

Factor H ◽

Vaccine Antigen

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Determination of serotyping antigens, clonal analysis and genetic characterization of the 4CMenB vaccine antigen genes in invasive Neisseria meningitidis from Western Canada, 2009 to 2013

Journal of Medical Microbiology ◽

10.1099/jmm.0.079921-0 ◽

2014 ◽

Vol 63 (11) ◽

pp. 1490-1499 ◽

Cited By ~ 7

Author(s):

Dennis K. S. Law ◽

Jianwei Zhou ◽

Saul Deng ◽

Linda Hoang ◽

Gregory Tyrrell ◽

...

Keyword(s):

Neisseria Meningitidis ◽

Clonal Complex ◽

Factor H ◽

Vaccine Antigen ◽

Western Canada ◽

Antigenic Analysis ◽

Clonal Nature ◽

4Cmenb Vaccine

This study examined invasive Neisseria meningitidis recovered from invasive meningococcal disease (IMD) cases in Western Canada between 2009 and 2013. A total of 161 isolates from individual IMD cases were analysed for serogroup, serotype, serosubtype, PorA genotype, multi-locus sequence type and nucleotide sequence of their 4CMenB vaccine antigen genes. Sixty-nine isolates were serogroup B (MenB), 47 were serogroup Y (MenY), 22 were serogroup C (MenC), 19 were serogroup W (MenW), three were serogroup E and one was non-encapsulated. MenC, MenY and MenW were mainly clonal, represented primarily by clonal complex (cc) 11, cc23 or cc167, and cc22, respectively. In contrast, MenB were composed of eight different ccs together with 11 isolates not assigned to any known cc. Antigenic analysis and PorA genotyping confirmed the heterogeneity of MenB isolates, while such results supported the clonal nature of most MenC, MenY and MenW isolates. Thirty-four (21.1 %) isolates had at least one gene that encoded one matching vaccine protein component of the 4CMenB vaccine (i.e. PorA P1.4; fHbp variant 1.1; NHBA peptide 2; and NadA-1, -2, or -3). An additional 18 isolates had genes that encoded variant 1 or subfamily B factor H binding proteins of this same vaccine.

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