Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles

Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1–P4)were...

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Main Authors: Chan, Yanqi, Jazayeri, S. D. *, Ramanathan, Babu *, Poh, Chit Laa *
Format: Article
Language:English
Published: MDPI 2020
Subjects:
Online Access:http://eprints.sunway.edu.my/1343/
http://eprints.sunway.edu.my/1343/1/Poh%20Chit%20Laa%20Enhancement%20of%20tetravalent.pdf
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author Chan, Yanqi
Jazayeri, S. D. *
Ramanathan, Babu *
Poh, Chit Laa *
author_facet Chan, Yanqi
Jazayeri, S. D. *
Ramanathan, Babu *
Poh, Chit Laa *
author_sort Chan, Yanqi
building SU Institutional Repository
collection Online Access
description Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1–P4)were designed by linking a universal T-helper epitope (PADREorTpD) to the highly conserved CD8 T cell epitope and B cell epitope (B1 or B2) against all four DENV serotypes. The multi-epitope peptides were conjugated to polystyrene nanoparticles (PSNPs) and four nanovaccines (NP1–NP4) were constructed. Mice immunized with NP1–NP4 elicited significantly higher titers of IgG and neutralizing antibodies when compared to immunization with naked P1–P4. The immune responses in mice immunized with peptide vaccines were compared with nanovaccines using ELISA, ELISPOT, and a neutralization test based on FRNT50. Among the four conjugated peptide nanovaccines, NP3comprisingtheTpDT-helper epitope linked to the highly conserved B1 epitope derived from the E protein was able to elicit significant levels of IFN-γ and neutralizing antibodies to all four dengue serotypes. NP3 is a promising tetravalent synthetic peptide vaccine, but the selection of a more effective CD8+ T cell epitope and adjuvants to further improve the immunogenicity is warranted.
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spelling sunway-13432020-08-24T03:10:13Z http://eprints.sunway.edu.my/1343/ Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles Chan, Yanqi Jazayeri, S. D. * Ramanathan, Babu * Poh, Chit Laa * QR355 Virology Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1–P4)were designed by linking a universal T-helper epitope (PADREorTpD) to the highly conserved CD8 T cell epitope and B cell epitope (B1 or B2) against all four DENV serotypes. The multi-epitope peptides were conjugated to polystyrene nanoparticles (PSNPs) and four nanovaccines (NP1–NP4) were constructed. Mice immunized with NP1–NP4 elicited significantly higher titers of IgG and neutralizing antibodies when compared to immunization with naked P1–P4. The immune responses in mice immunized with peptide vaccines were compared with nanovaccines using ELISA, ELISPOT, and a neutralization test based on FRNT50. Among the four conjugated peptide nanovaccines, NP3comprisingtheTpDT-helper epitope linked to the highly conserved B1 epitope derived from the E protein was able to elicit significant levels of IFN-γ and neutralizing antibodies to all four dengue serotypes. NP3 is a promising tetravalent synthetic peptide vaccine, but the selection of a more effective CD8+ T cell epitope and adjuvants to further improve the immunogenicity is warranted. MDPI 2020-07-25 Article PeerReviewed text en cc_by_nc_4 http://eprints.sunway.edu.my/1343/1/Poh%20Chit%20Laa%20Enhancement%20of%20tetravalent.pdf Chan, Yanqi and Jazayeri, S. D. * and Ramanathan, Babu * and Poh, Chit Laa * (2020) Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles. Vaccines, 8 (3). p. 417. ISSN 2076-393X http://doi.org/10.3390/vaccines8030417 doi:10.3390/vaccines8030417
spellingShingle QR355 Virology
Chan, Yanqi
Jazayeri, S. D. *
Ramanathan, Babu *
Poh, Chit Laa *
Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles
title Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles
title_full Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles
title_fullStr Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles
title_full_unstemmed Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles
title_short Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles
title_sort enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles
topic QR355 Virology
url http://eprints.sunway.edu.my/1343/
http://eprints.sunway.edu.my/1343/
http://eprints.sunway.edu.my/1343/
http://eprints.sunway.edu.my/1343/1/Poh%20Chit%20Laa%20Enhancement%20of%20tetravalent.pdf