A DNA vaccine against yellow fever virus: development and evaluation.
Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizi...
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ftdoajarticles:oai:doaj.org/article:abc87adce0a34a988157153ae89578df 2023-05-15T15:13:06+02:00 A DNA vaccine against yellow fever virus: development and evaluation. Milton Maciel Fábia da Silva Pereira Cruz Marli Tenório Cordeiro Márcia Archer da Motta Klécia Marília Soares de Melo Cassemiro Rita de Cássia Carvalho Maia Regina Célia Bressan Queiroz de Figueiredo Ricardo Galler Marcos da Silva Freire Joseph Thomas August Ernesto T A Marques Rafael Dhalia 2015-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003693 https://doaj.org/article/abc87adce0a34a988157153ae89578df EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4395287?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003693 https://doaj.org/article/abc87adce0a34a988157153ae89578df PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003693 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003693 2022-12-31T12:30:46Z Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 4 e0003693 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Milton Maciel Fábia da Silva Pereira Cruz Marli Tenório Cordeiro Márcia Archer da Motta Klécia Marília Soares de Melo Cassemiro Rita de Cássia Carvalho Maia Regina Célia Bressan Queiroz de Figueiredo Ricardo Galler Marcos da Silva Freire Joseph Thomas August Ernesto T A Marques Rafael Dhalia A DNA vaccine against yellow fever virus: development and evaluation. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies. |
format |
Article in Journal/Newspaper |
author |
Milton Maciel Fábia da Silva Pereira Cruz Marli Tenório Cordeiro Márcia Archer da Motta Klécia Marília Soares de Melo Cassemiro Rita de Cássia Carvalho Maia Regina Célia Bressan Queiroz de Figueiredo Ricardo Galler Marcos da Silva Freire Joseph Thomas August Ernesto T A Marques Rafael Dhalia |
author_facet |
Milton Maciel Fábia da Silva Pereira Cruz Marli Tenório Cordeiro Márcia Archer da Motta Klécia Marília Soares de Melo Cassemiro Rita de Cássia Carvalho Maia Regina Célia Bressan Queiroz de Figueiredo Ricardo Galler Marcos da Silva Freire Joseph Thomas August Ernesto T A Marques Rafael Dhalia |
author_sort |
Milton Maciel |
title |
A DNA vaccine against yellow fever virus: development and evaluation. |
title_short |
A DNA vaccine against yellow fever virus: development and evaluation. |
title_full |
A DNA vaccine against yellow fever virus: development and evaluation. |
title_fullStr |
A DNA vaccine against yellow fever virus: development and evaluation. |
title_full_unstemmed |
A DNA vaccine against yellow fever virus: development and evaluation. |
title_sort |
dna vaccine against yellow fever virus: development and evaluation. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003693 https://doaj.org/article/abc87adce0a34a988157153ae89578df |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003693 (2015) |
op_relation |
http://europepmc.org/articles/PMC4395287?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003693 https://doaj.org/article/abc87adce0a34a988157153ae89578df |
op_doi |
https://doi.org/10.1371/journal.pntd.0003693 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
4 |
container_start_page |
e0003693 |
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1766343692705071104 |