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Vaccine antigen, Factor H binding protein, is typically a non-lipidated precursor that localises to the meningococcal surface by Slam

RAG da Silva, AV Karlyshev, NJ Oldfield, KG Wooldridge, CD Bayliss, A Ryan, View ORCID ProfileR Griffin
doi: https://doi.org/10.1101/693374
RAG da Silva
aCentre for Biomolecular Sciences, University Park, University of Nottingham, NG7 2RD, UK
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AV Karlyshev
bSchool of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston upon Thames, KT1 2EE, UK
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NJ Oldfield
aCentre for Biomolecular Sciences, University Park, University of Nottingham, NG7 2RD, UK
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KG Wooldridge
aCentre for Biomolecular Sciences, University Park, University of Nottingham, NG7 2RD, UK
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CD Bayliss
cDepartment of Genetics and Genome Biology, University of Leicester, University Road, Leicester, LE1 7RH, UK
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A Ryan
bSchool of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston upon Thames, KT1 2EE, UK
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R Griffin
aCentre for Biomolecular Sciences, University Park, University of Nottingham, NG7 2RD, UK
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  • ORCID record for R Griffin
  • For correspondence: ruth.griffin1@nottingham.ac.uk
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Abstract

Meningococcal surface lipoprotein, Factor H binding protein (FHbp), is the sole antigen of the Trumenba vaccine (Pfizer) and one of four antigens of the Bexsero vaccine (GSK) targeting Neisseria meningitidis serogroup B isolates. Lipidation of FHbp is assumed to occur for all isolates and its surface localisation is conducted by surface lipoprotein assembly modulator, Slam.

We show in 91% of a collection of UK isolates (1742/1895) non-synonymous single nucleotide polymorphisms (SNPs) in the signal peptide of FHbp. A single SNP, common to all, alters a polar amino acid that abolishes processing, including lipidation and signal peptide cleavage. Rather than the toxic accumulation of the precursor in the periplasm as expected from disrupting the canonical processing pathway, remarkably the FHbp precursor is translocated to the outer membrane and surface-localised by Slam. Thus we show Slam is not lipoprotein-specific. In a panel of isolates expressing precursor FHbp at the surface, we investigated their binding to human factor H and their susceptibility to antibody-mediated killing. Our findings have implications for Trumenba and Bexsero and provide key insights for lipoprotein-based vaccines in development.

Footnotes

  • http://flowrepository.org/id/RvFrLUcAM69ZrTziXZJn622NsvQgwRuVqoRC28XA9wBxR2KZsAJ2yym5ToAfMt6p

  • http://flowrepository.org/id/RvFryhGbJHv5UMqqZ1bEfLEz6aO8QEV0EsQtjKdcSjlMt1rCtFIiT9HmOrMZYBms

  • http://flowrepository.org/id/RvFraaVCkdcJJYpYJOc4CFQNbETeVGwTy1bcNwXpA3YotemW9trGUDNKJFgxXnKi

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 08, 2019.
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Vaccine antigen, Factor H binding protein, is typically a non-lipidated precursor that localises to the meningococcal surface by Slam
RAG da Silva, AV Karlyshev, NJ Oldfield, KG Wooldridge, CD Bayliss, A Ryan, R Griffin
bioRxiv 693374; doi: https://doi.org/10.1101/693374
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Vaccine antigen, Factor H binding protein, is typically a non-lipidated precursor that localises to the meningococcal surface by Slam
RAG da Silva, AV Karlyshev, NJ Oldfield, KG Wooldridge, CD Bayliss, A Ryan, R Griffin
bioRxiv 693374; doi: https://doi.org/10.1101/693374

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