Assessment of vaccine potential of the Neisseria-specific protein NMB0938

Gretel Sardiñas*, Yanet Climent, Yaindrys Rodríguez, Sonia González, Darién García, Karem Cobas, Evelin Caballero, Yusleydis Pérez, Charlotte Brookes, Stephen Taylor, Andrew Gorringe, Maité Delgado, Rolando Pajón, Daniel Yero

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The availability of complete genome sequence of Neisseria meningitidis serogroup B strain MC58 and reverse vaccinology has allowed the discovery of several novel antigens. Here, we have explored the potential of N. meningitidis lipoprotein NMB0938 as a vaccine candidate, based on investigation of gene sequence conservation and the antibody response elicited after immunization in mice. This antigen was previously identified by a genome-based approach as an outer membrane lipoprotein unique to the Neisseria genus. The nmb0938 gene was present in all 37 Neisseria isolates analyzed in this study. Based on amino acid sequence identity, 16 unique sequences were identified which clustered into three variants with identities ranging from 92 to 99%, with one cluster represented by the Neisseria lactamica strains. Recombinant protein NMB0938 (rNMB0938) was expressed in Escherichia coli and purified after solubilization of the insoluble fraction. Antisera produced in mice against purified rNMB0938 reacted with a range of meningococcal strains in whole-cell ELISA and western blotting. Using flow cytometry, it was also shown that anti-rNMB0938 antibodies bound to the surface of the homologous meningococcal strain and activated complement deposition. Moreover, antibodies against rNMB0938 elicited complement-mediated killing of meningococcal strains from both sequence variants and conferred passive protection against meningococcal bacteremia in infant rats. According to our results, NMB0938 represents a promising candidate to be included in a vaccine to prevent meningococcal disease.

Original languageEnglish
Pages (from-to)6910-6917
Number of pages8
JournalVaccine
Volume27
Issue number49
DOIs
Publication statusPublished - 16 Nov 2009

Bibliographical note

Funding Information:
The authors would like to thank Thomas E. Vaughan (HPA, Porton Down, UK) for providing us the unassembled N. lactamica Y92-1009 genome. Research at the Health Protection Agency was funded by the UK Department of Health .

Keywords

  • Meningococcus serogroup B
  • Sequence variability
  • Surface antigen

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