PXD058197

PXD058197 is an original dataset announced via ProteomeXchange.

Title	Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA
Description	The structure and conformation adopted by protein vaccine antigens significantly influence the exposure of their antigenic determinants. Structural knowledge of antigens in native state could drive the design of recombinant vaccines that resemble their cognate native forms, although such information is often difficult to obtain, particularly for membrane proteins. Here, we assessed the structural and functional features of the native Neisseria Adhesin A (NadA), a meningococcal trimeric outer membrane protein included as soluble recombinant antigen in the 4CMenB vaccine. We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to generate a structural model of NadA and to compare the fold and structural dynamics of the recombinant NadA as soluble vaccine form, and the native NadA in situ, as embedded in meningococcal outer membrane vesicles (OMVs), complementing the HDX data with electron microscopy imaging. While their overall structures are similar, conformational differences between the two forms were observed. Especially, OMV- embedded NadA appears more susceptible to trimer opening than its cognate soluble antigen, suggesting that NadA in its native membrane could display a larger antigenic surface. Accordingly, we show that mice immunized with OMV-embedded NadA elicited antibodies with superior bactericidal activity and capable of better preventing bacterial adhesion compared to the soluble antigen. Collectively, these data support the hypothesis that protein vaccine antigens presented in native-like environments can elicit a more potent immune response than recombinant forms.
HostingRepository	PRIDE
AnnounceDate	2025-09-15
AnnouncementXML	Submission_2025-09-15_10:48:59.084.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Valeria Calvaresi
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-24 11:57:49	ID requested
⏵ 1	2025-09-15 10:48:59	announced

Dataset with its publication pending

submitter keyword: NadA, HDX-MS

Nathalie Norais
contact affiliation	GlaxoSmithKline, Siena, Italy
contact email	nathalie.x.norais@gsk.com
lab head
Valeria Calvaresi
contact affiliation	University of Oxford
contact email	valeria.calvaresi@bioch.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058197
     1. Label: PRIDE project
     2. Name: Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA