A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection.
BACKGROUND: Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing an important disease in ruminants often transmitted to humans after epizootic outbreaks in African and Arabian countries. To help combat the spread of the disease, prophylactic measures need to be developed and/or improv...
Published in: | PLoS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0002309 https://doaj.org/article/7e5ed1c94344481083e58288329c575e |
id |
ftdoajarticles:oai:doaj.org/article:7e5ed1c94344481083e58288329c575e |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:7e5ed1c94344481083e58288329c575e 2023-05-15T15:15:48+02:00 A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection. Elena López-Gil Gema Lorenzo Esther Hevia Belén Borrego Martin Eiden Martin Groschup Sarah C Gilbert Alejandro Brun 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002309 https://doaj.org/article/7e5ed1c94344481083e58288329c575e EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3708870?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002309 https://doaj.org/article/7e5ed1c94344481083e58288329c575e PLoS Neglected Tropical Diseases, Vol 7, Iss 7, p e2309 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002309 2022-12-31T13:43:46Z BACKGROUND: Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing an important disease in ruminants often transmitted to humans after epizootic outbreaks in African and Arabian countries. To help combat the spread of the disease, prophylactic measures need to be developed and/or improved. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we evaluated the immunogenicity and protective efficacy of recombinant plasmid DNA and modified vaccinia virus Ankara (rMVA) vectored vaccines against Rift Valley fever in mice. These recombinant vaccines encoded either of two components of the Rift Valley fever virus: the viral glycoproteins (Gn/Gc) or the nucleoprotein (N). Following lethal challenge with live RVFV, mice immunized with a single dose of the rMVA-Gn/Gc vaccine showed no viraemia or clinical manifestation of disease, but mounted RVFV neutralizing antibodies and glycoprotein specific CD8+ T-cell responses. Neither DNA-Gn/Gc alone nor a heterologous prime-boost immunization schedule (DNA-Gn/Gc followed by rMVAGn/Gc) was better than the single rMVA-Gn/Gc immunization schedule with regards to protective efficacy. However, the rMVA-Gn/Gc vaccine failed to protect IFNAR(-/-) mice upon lethal RVFV challenge suggesting a role for innate responses in protection against RVFV. Despite induction of high titer antibodies against the RVFV nucleoprotein, the rMVA-N vaccine, whether in homologous or heterologous prime-boost schedules with the corresponding recombinant DNA vaccine, only conferred partial protection to RVFV challenge. CONCLUSIONS/SIGNIFICANCE: Given the excellent safety profile of rMVA based vaccines in humans and animals, our data supports further development of rMVA-Gn/Gc as a vaccine strategy that can be used for the prevention of Rift Valley fever in both humans and livestock. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 7 e2309 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Elena López-Gil Gema Lorenzo Esther Hevia Belén Borrego Martin Eiden Martin Groschup Sarah C Gilbert Alejandro Brun A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing an important disease in ruminants often transmitted to humans after epizootic outbreaks in African and Arabian countries. To help combat the spread of the disease, prophylactic measures need to be developed and/or improved. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we evaluated the immunogenicity and protective efficacy of recombinant plasmid DNA and modified vaccinia virus Ankara (rMVA) vectored vaccines against Rift Valley fever in mice. These recombinant vaccines encoded either of two components of the Rift Valley fever virus: the viral glycoproteins (Gn/Gc) or the nucleoprotein (N). Following lethal challenge with live RVFV, mice immunized with a single dose of the rMVA-Gn/Gc vaccine showed no viraemia or clinical manifestation of disease, but mounted RVFV neutralizing antibodies and glycoprotein specific CD8+ T-cell responses. Neither DNA-Gn/Gc alone nor a heterologous prime-boost immunization schedule (DNA-Gn/Gc followed by rMVAGn/Gc) was better than the single rMVA-Gn/Gc immunization schedule with regards to protective efficacy. However, the rMVA-Gn/Gc vaccine failed to protect IFNAR(-/-) mice upon lethal RVFV challenge suggesting a role for innate responses in protection against RVFV. Despite induction of high titer antibodies against the RVFV nucleoprotein, the rMVA-N vaccine, whether in homologous or heterologous prime-boost schedules with the corresponding recombinant DNA vaccine, only conferred partial protection to RVFV challenge. CONCLUSIONS/SIGNIFICANCE: Given the excellent safety profile of rMVA based vaccines in humans and animals, our data supports further development of rMVA-Gn/Gc as a vaccine strategy that can be used for the prevention of Rift Valley fever in both humans and livestock. |
format |
Article in Journal/Newspaper |
author |
Elena López-Gil Gema Lorenzo Esther Hevia Belén Borrego Martin Eiden Martin Groschup Sarah C Gilbert Alejandro Brun |
author_facet |
Elena López-Gil Gema Lorenzo Esther Hevia Belén Borrego Martin Eiden Martin Groschup Sarah C Gilbert Alejandro Brun |
author_sort |
Elena López-Gil |
title |
A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection. |
title_short |
A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection. |
title_full |
A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection. |
title_fullStr |
A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection. |
title_full_unstemmed |
A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection. |
title_sort |
single immunization with mva expressing gngc glycoproteins promotes epitope-specific cd8+-t cell activation and protects immune-competent mice against a lethal rvfv infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002309 https://doaj.org/article/7e5ed1c94344481083e58288329c575e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 7, p e2309 (2013) |
op_relation |
http://europepmc.org/articles/PMC3708870?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002309 https://doaj.org/article/7e5ed1c94344481083e58288329c575e |
op_doi |
https://doi.org/10.1371/journal.pntd.0002309 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
7 |
container_issue |
7 |
container_start_page |
e2309 |
_version_ |
1766346143843745792 |