We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Harnessing Pentameric Scaffold of Cholera Toxin B (CTB) for Design of Subvirion Recombinant Dengue Virus Vaccine.
- Authors
Sung, Jemin; Cheong, Yucheol; Kim, Young-Seok; Ahn, Jina; Sohn, Myung Hyun; Byun, Sanguine; Seong, Baik-Lin
- Abstract
Dengue virus is an enveloped virus with an icosahedral assembly of envelope proteins (E). The E proteins are arranged as a head-to-tail homodimer, and domain III (EDIII) is placed at the edge of the dimer, converging to a pentamer interface. For a structure-based approach, cholera toxin B (CTB) was harnessed as a structural scaffold for the five-fold symmetry of EDIII. Pivoted by an RNA-mediated chaperone for the protein folding and assembly, CTB-EDIII of dengue serotype 1 (DV1) was successfully produced as soluble pentamers in an E. coli host with a high yield of about 28 mg/L. Immunization of mice with CTB-DV1EDIII elicited increased levels of neutralizing antibodies against infectious viruses compared to the control group immunized with DV1EDIII without CTB fusion. IgG isotype switching into a balanced Th1/Th2 response was also observed, probably triggered by the intrinsic adjuvant activity of CTB. Confirming the immune-enhancing potential of CTB in stabilizing the pentamer assembly of EDIII, this study introduces a low-cost bacterial production platform designed to augment the soluble production of subunit vaccine candidates, particularly those targeting flaviviruses.
- Subjects
CHOLERA toxin; DENGUE viruses; RECOMBINANT viruses; VIRAL vaccines; MOLECULAR chaperones
- Publication
Vaccines, 2024, Vol 12, Issue 1, p92
- ISSN
2076-393X
- Publication type
Article
- DOI
10.3390/vaccines12010092