{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schneck NA"],"funding":["Intramural NIH HHS"],"pagination":["2576-2579"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7780558"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(12)"],"pubmed_abstract":["A hemagglutinin stabilized stem nanoparticle (HA-SS-np) that is designed to provide broad protection against influenza is being developed as a potential vaccine. During an early formulation screening study, reducing gel (rCGE) analysis indicated product degradation in a few candidate buffers at the first-week accelerated stability point, whereas no change was shown in the size exclusion chromatography (SEC) measurement. A LC-MS workflow was therefore applied to investigate the integrity of this large HA-SS-np vaccine molecule (≈ 1 MDa). Application of LC-MS was critical to rationalize the conflicting results from the rCGE and SEC assays and led to the discovery that (1) an unexpected sequence clipping in the HA-SS-np subunits occurred, explaining the atypical reducing gel profile, and (2) an undisrupted disulfide bond held the two fragments together, explaining the unchanged SEC profile. This analytical case study led to a formulation buffer redesign, which mitigated the issue."],"journal":["Journal of the American Society for Mass Spectrometry"],"pubmed_title":["Using LC-MS to Identify Clipping in Self-Assembled Nanoparticles During Vaccine Development."],"pmcid":["PMC7780558"],"funding_grant_id":["Z99 AI999999"],"pubmed_authors":["Lei QP","Cooper JW","Schneck NA","Gollapudi D","Rosales-Zavala E","Wang X","Ivleva VB"],"additional_accession":[]},"is_claimable":false,"name":"Using LC-MS to Identify Clipping in Self-Assembled Nanoparticles During Vaccine Development.","description":"A hemagglutinin stabilized stem nanoparticle (HA-SS-np) that is designed to provide broad protection against influenza is being developed as a potential vaccine. During an early formulation screening study, reducing gel (rCGE) analysis indicated product degradation in a few candidate buffers at the first-week accelerated stability point, whereas no change was shown in the size exclusion chromatography (SEC) measurement. A LC-MS workflow was therefore applied to investigate the integrity of this large HA-SS-np vaccine molecule (≈ 1 MDa). Application of LC-MS was critical to rationalize the conflicting results from the rCGE and SEC assays and led to the discovery that (1) an unexpected sequence clipping in the HA-SS-np subunits occurred, explaining the atypical reducing gel profile, and (2) an undisrupted disulfide bond held the two fragments together, explaining the unchanged SEC profile. This analytical case study led to a formulation buffer redesign, which mitigated the issue.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Dec","modification":"2024-11-07T13:14:18.529Z","creation":"2021-02-20T18:00:19Z"},"accession":"S-EPMC7780558","cross_references":{"pubmed":["31595432"],"doi":["10.1007/s13361-019-02318-z"]}}