Ronni A.G. da Silva
Variant Signal Peptides of Vaccine Antigen, FHbp, Impair Processing Affecting Surface Localization and Antibody-Mediated Killing in Most Meningococcal Isolates
da Silva, Ronni A.G.; Karlyshev, Andrey V.; Oldfield, Neil J.; Wooldridge, Karl G.; Bayliss, Christopher D.; Ryan, Ali; Griffin, Ruth
Authors
Andrey V. Karlyshev
NEIL OLDFIELD NEIL.OLDFIELD@NOTTINGHAM.AC.UK
Assistant Professor
KARL WOOLDRIDGE KARL.WOOLDRIDGE@NOTTINGHAM.AC.UK
Associate Professor
Christopher D. Bayliss
Ali Ryan
RUTH GRIFFIN Ruth.Griffin1@nottingham.ac.uk
Assistant Professor
Abstract
© Copyright © 2019 da Silva, Karlyshev, Oldfield, Wooldridge, Bayliss, Ryan and Griffin. Meningococcal 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. We show in the majority of a collection of United Kingdom isolates (1742/1895) non-synonymous single nucleotide polymorphisms (SNPs) in the signal peptide (SP) of FHbp. A single SNP, common to all, alters a polar amino acid that abolishes processing: lipidation and SP cleavage. Whilst some of the FHbp precursor is retained in the cytoplasm due to reduced binding to SecA, remarkably some is translocated and further surface-localized by Slam. Thus we show Slam is not lipoprotein-specific. In a panel of isolates tested, the overall reduced surface localization of the precursor FHbp, compared to isolates with an intact SP, corresponded with decreased susceptibility to antibody-mediated killing. Our findings shed new light on the canonical pathway for lipoprotein processing and translocation of important relevance for lipoprotein-based vaccines in development and in particular for Trumenba.
Citation
da Silva, R. A., Karlyshev, A. V., Oldfield, N. J., Wooldridge, K. G., Bayliss, C. D., Ryan, A., & Griffin, R. (2019). Variant Signal Peptides of Vaccine Antigen, FHbp, Impair Processing Affecting Surface Localization and Antibody-Mediated Killing in Most Meningococcal Isolates. Frontiers in Microbiology, 10, Article 2847. https://doi.org/10.3389/fmicb.2019.02847
Journal Article Type | Article |
---|---|
Acceptance Date | Nov 25, 2019 |
Online Publication Date | Dec 19, 2019 |
Publication Date | Dec 19, 2019 |
Deposit Date | Nov 27, 2019 |
Publicly Available Date | Dec 19, 2019 |
Journal | Frontiers in Microbiology |
Electronic ISSN | 1664-302X |
Publisher | Frontiers Media |
Peer Reviewed | Peer Reviewed |
Volume | 10 |
Article Number | 2847 |
DOI | https://doi.org/10.3389/fmicb.2019.02847 |
Keywords | Meningoccocus; FHbp; Vaccine; Signal peptide; Lipoprotein; Lnt; Slam |
Public URL | https://nottingham-repository.worktribe.com/output/3419927 |
Publisher URL | https://www.frontiersin.org/articles/10.3389/fmicb.2019.02847/full |
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Variant Signal Peptides of Vaccine Antigen, FHbp, Impair Processing Affecting Surface Localization and Antibody-Mediated Killing in Most Meningococcal Isolates
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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