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Display of FliC131 on the Surface of Lactococcus lactis as a Strategy to Increase its Adjuvanticity for Mucosal Immunization.
- Source :
-
Journal of pharmaceutical sciences [J Pharm Sci] 2024 Jul; Vol. 113 (7), pp. 1794-1803. Date of Electronic Publication: 2024 Mar 22. - Publication Year :
- 2024
-
Abstract
- Research on innovative mucosal adjuvants is essential to develop new vaccines for safe mucosal application. In this work, we propose the development of a Lactococcus lactis that expresses a variant of flagellin on its surface (FliC131*), to increase the adjuvanticity of the living cell and cell wall-derived particles (CWDP). We optimized the expression of FliC131*, and confirmed its identity and localization by Western blot and flow cytometry. We also generated CWDP containing FliC131* (CDWP-FliC131*) and evaluated their storage stability. Lastly, we measured the human TLR5 stimulating activity in vitro and assessed the adjuvanticity in vivo using ovalbumin (OVA) as a model antigen. As a result, we generated L. lactis/pCWA-FliC131*, that expresses and displays FliC131* on its surface, obtained the corresponding CWDP-FliC131*, and showed that both activated hTLR5 in vitro in a dose-dependent manner. Furthermore, CWDP-FliC131* retained this biological activity after being lyophilized and stored for a year. Finally, intranasal immunization of mice with OVA plus live L. lactis/pCWA-FliC131* or CWDP-FliC131* induced OVA-specific IgG and IgA in serum, intestinal lavages, and bronchoalveolar lavages. Our work demonstrates the potential of this recombinant L. lactis with an enhanced adjuvant effect, prompting its further evaluation for the design of novel mucosal vaccines.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Humans
Female
Immunity, Mucosal drug effects
Immunity, Mucosal immunology
Immunization methods
Administration, Intranasal
Lactococcus lactis immunology
Flagellin immunology
Flagellin administration & dosage
Ovalbumin immunology
Ovalbumin administration & dosage
Toll-Like Receptor 5 immunology
Adjuvants, Immunologic administration & dosage
Mice, Inbred BALB C
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6017
- Volume :
- 113
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 38522753
- Full Text :
- https://doi.org/10.1016/j.xphs.2024.03.013