ATTENTION: The software behind KU ScholarWorks is being upgraded to a new version. Starting July 15th, users will not be able to log in to the system, add items, nor make any changes until the new version is in place at the end of July. Searching for articles and opening files will continue to work while the system is being updated.
If you have any questions, please contact Marianne Reed at mreed@ku.edu .
A Combined LC-MS and Immunoassay Approach to Characterize Preservative-Induced Destabilization of Human Papillomavirus Virus-like Particles Adsorbed to an Aluminum-Salt Adjuvant (Dataset)
dc.contributor.author | Caringal, Ria T. | |
dc.contributor.author | Hickey, John M. | |
dc.contributor.author | Sharma, Nitya | |
dc.contributor.author | Jerajani, Kaushal | |
dc.contributor.author | Bewaji, Oluwadara | |
dc.contributor.author | Brendle, Sarah | |
dc.contributor.author | Christensen, Neil | |
dc.contributor.author | Batwal, Saurabh | |
dc.contributor.author | Mahedvi, Mustafa | |
dc.contributor.author | Rao, Harish | |
dc.contributor.author | Dogar, Vikas | |
dc.contributor.author | Chandrasekharan, Rahul | |
dc.contributor.author | Shaligram, Umesh | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Volkin, David B. | |
dc.date.accessioned | 2024-05-23T20:42:46Z | |
dc.date.available | 2024-05-23T20:42:46Z | |
dc.date.issued | 2024-05-23 | |
dc.identifier.uri | https://hdl.handle.net/1808/35060 | |
dc.description.abstract | During the multi-dose formulation development of recombinant vaccine candidates, protein antigens can be destabilized by antimicrobial preservatives (APs). The degradation mechanisms are often poorly understood since available analytical tools are limited due to low protein concentrations and the presence of adjuvants. In this work, we evaluate different analytical approaches to monitor the structural integrity of HPV16 VLPs adsorbed to Alhydrogel™ (AH) in the presence and absence of APs (i.e., destabilizing m-cresol, MC or non-destabilizing chlorobutanol, CB) under accelerated conditions (pH 7.4, 50°C). First, in vitro potency losses displayed only modest correlations with the results from two commonly used methods of protein analysis (SDS-PAGE, DSC). Next, results from two alternative analytical approaches provided a better understanding of physicochemical events occurring under these same conditions: (1) competitive ELISA immunoassays with a panel of mAbs against conformational and linear epitopes on HPV16 VLPs, and (2) LC-MS peptide mapping to evaluate the accessibility/redox state of the 12 cysteine residues within each L1 protein compising the HPV16 VLP (i.e., with 360 L1 proteins per VLP, there are 4,320 Cys residues per VLP). These methods expand the limited analytical toolset currently available to characterize AH-adsorbed antigens and provide additional insights into the molecular mechanism(s) of AP-induced destabilization of vaccine antigens. | en_US |
dc.publisher | MDPI | en_US |
dc.rights | © 2024 The Author(s). | |
dc.subject | Vaccine | en_US |
dc.subject | Stability | en_US |
dc.subject | Adjuvant | en_US |
dc.subject | Preservatives | en_US |
dc.subject | Alhydrogel | en_US |
dc.subject | Human papillomavirus | en_US |
dc.subject | Virus-like particles | en_US |
dc.subject | ELISA | en_US |
dc.subject | Cysteine | en_US |
dc.title | A Combined LC-MS and Immunoassay Approach to Characterize Preservative-Induced Destabilization of Human Papillomavirus Virus-like Particles Adsorbed to an Aluminum-Salt Adjuvant (Dataset) | en_US |
dc.type | Dataset | en_US |
kusw.kuauthor | Hickey, John M. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | https://doi.org/10.17161/1808.35060 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8818-6708 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-2714-5352 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3269-9106 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-2301-2595 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-1448-1998 | en_US |
dc.rights.accessrights | openAccess | en_US |