Cargando…
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) we...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563452/ https://www.ncbi.nlm.nih.gov/pubmed/32722368 http://dx.doi.org/10.3390/vaccines8030417 |
_version_ | 1783595492162142208 |
---|---|
author | Chan, Yanqi Jazayeri, Seyed Davoud Ramanathan, Babu Poh, Chit Laa |
author_facet | Chan, Yanqi Jazayeri, Seyed Davoud Ramanathan, Babu Poh, Chit Laa |
author_sort | Chan, Yanqi |
collection | PubMed |
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 (PADRE or TpD) 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 FRNT(50). Among the four conjugated peptide nanovaccines, NP3 comprising the TpD T-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. |
format | Online Article Text |
id | pubmed-7563452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75634522020-10-27 Enhancement of Tetravalent Immune Responses to Highly Conserved Epitopes of a Dengue Peptide Vaccine Conjugated to Polystyrene Nanoparticles Chan, Yanqi Jazayeri, Seyed Davoud Ramanathan, Babu Poh, Chit Laa Vaccines (Basel) Article 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 (PADRE or TpD) 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 FRNT(50). Among the four conjugated peptide nanovaccines, NP3 comprising the TpD T-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 /pmc/articles/PMC7563452/ /pubmed/32722368 http://dx.doi.org/10.3390/vaccines8030417 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chan, Yanqi Jazayeri, Seyed Davoud 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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563452/ https://www.ncbi.nlm.nih.gov/pubmed/32722368 http://dx.doi.org/10.3390/vaccines8030417 |
work_keys_str_mv | AT chanyanqi enhancementoftetravalentimmuneresponsestohighlyconservedepitopesofadenguepeptidevaccineconjugatedtopolystyrenenanoparticles AT jazayeriseyeddavoud enhancementoftetravalentimmuneresponsestohighlyconservedepitopesofadenguepeptidevaccineconjugatedtopolystyrenenanoparticles AT ramanathanbabu enhancementoftetravalentimmuneresponsestohighlyconservedepitopesofadenguepeptidevaccineconjugatedtopolystyrenenanoparticles AT pohchitlaa enhancementoftetravalentimmuneresponsestohighlyconservedepitopesofadenguepeptidevaccineconjugatedtopolystyrenenanoparticles |