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Determination of Conformational and Functional Stability of Potential Plague Vaccine Candidate in Formulation

Authors :
Krubha Athirathinam
Selvasudha Nandakumar
Shailendra Kumar Verma
Ruckmani Kandasamy
Source :
Vaccines, Vol 11, Iss 1, p 27 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Generally, protein-based vaccines are available in liquid form and are highly susceptible to instability under elevated temperature changes including freezing conditions. There is a need to create a convenient formulation of protein/peptides that can be stored at ambient conditions without loss of activity or production of adverse effects. The efficiency of naturally occurring biocompatible polymer dextran in improving the shelf-life and biological activity of a highly thermally unstable plague vaccine candidate protein called Low Calcium Response V antigen (LcrV), which can be stored at room temperature (30 ± 2 °C), has been evaluated. To determine the preferential interactions with molecular-level insight into solvent–protein interactions, analytical techniques such asspectroscopy, particle size distribution, gel electrophoresis, microscopy, and thermal analysis have been performed along with the evaluation of humoral immune response, invivo. The analytical methods demonstrate the structural stability of the LcrV protein by expressing its interaction with the excipients in the formulation. The invivo studies elicited the biological activity of the formulated antigen with a significantly higher humoral immune response (p-value = 0.047) when compared to the native, adjuvanted antigen. We propose dextran as a potential biopolymer with its co-excipient sodium chloride (NaCl) to provide protein compactness, i.e., prevent protein unfolding by molecular crowding or masking mechanism using preferential hydrophobic interaction for up to three weeks at room temperature (30 ± 2 °C).

Details

Language :
English
ISSN :
2076393X
Volume :
11
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Vaccines
Publication Type :
Academic Journal
Accession number :
edsdoj.7d71e2a51a064de480991db6e327c84e
Document Type :
article
Full Text :
https://doi.org/10.3390/vaccines11010027