A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model

Detalhes bibliográficos
Autor(a) principal: Keshwara, Rohan
Data de Publicação: 2019
Outros Autores: Hagen, Katie R., Abreu-Mota, Tiago, Papaneri, Amy B., Liu, David, Wirblich, Christoph, Johnson, Reed F., Schnell, Matthias J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/62296
Resumo: Accepted Manuscript
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spelling A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine ModelAnimalsAntibodies, NeutralizingAntibodies, ViralCell LineCercopithecus aethiopsDisease Models, AnimalFemaleGlycoproteinsHEK293 CellsHumansMarburg Virus DiseaseMarburgvirusMiceMice, Inbred BALB CMice, Inbred C57BLRabiesRabies VaccinesRabies virusVaccinationVero CellsViral VaccinesADCCantibody functionfilovirusimmunizationvaccineCiências Médicas::Medicina BásicaScience & TechnologyAccepted ManuscriptMarburg virus (MARV) is a filovirus related to Ebola virus (EBOV) associated with human hemorrhagic disease. Outbreaks are sporadic and severe, with a reported case mortality rate of upward of 88%. There is currently no antiviral or vaccine available. Given the sporadic nature of outbreaks, vaccines provide the best approach for long-term control of MARV in regions of endemicity. We have developed an inactivated rabies virus-vectored MARV vaccine (FILORAB3) to protect against Marburg virus disease. Immunogenicity studies in our labs have shown that a Th1-biased seroconversion to both rabies virus and MARV glycoproteins (GPs) is beneficial for protection in a preclinical murine model. As such, we adjuvanted FILORAB3 with glucopyranosyl lipid adjuvant (GLA), a Toll-like receptor 4 agonist, in a squalene-in-water emulsion. Across two different BALB/c mouse challenge models, we achieved 92% protection against murine-adapted Marburg virus (ma-MARV). Although our vaccine elicited strong MARV GP antibodies, it did not strongly induce neutralizing antibodies. Through both in vitro and in vivo approaches, we elucidated a critical role for NK cell-dependent antibody-mediated cellular cytotoxicity (ADCC) in vaccine-induced protection. Overall, these findings demonstrate that FILORAB3 is a promising vaccine candidate for Marburg virus disease.IMPORTANCE Marburg virus (MARV) is a virus similar to Ebola virus and also causes a hemorrhagic disease which is highly lethal. In contrast to EBOV, only a few vaccines have been developed against MARV, and researchers do not understand what kind of immune responses are required to protect from MARV. Here we show that antibodies directed against MARV after application of our vaccine protect in an animal system but fail to neutralize the virus in a widely used virus neutralization assay against MARV. This newly discovered activity needs to be considered more when analyzing MARV vaccines or infections.This work was funded in part through the U.S. National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research and the NIAID Division of Clinical Research. Battelle Memorial Institute's prime contract with the NIAID is under contract no. HHSN272200700016I.American Society for MicrobiologyUniversidade do MinhoKeshwara, RohanHagen, Katie R.Abreu-Mota, TiagoPapaneri, Amy B.Liu, DavidWirblich, ChristophJohnson, Reed F.Schnell, Matthias J.20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/62296engKeshwara, R., Hagen, K. R., Abreu-Mota, T., et. al. (2019). A Recombinant Rabies Virus Expressing the Marburg Virus Glycoprotein Is Dependent upon Antibody-Mediated Cellular Cytotoxicity for Protection against Marburg Virus Disease in a Murine Model. Journal of virology, 93(6), e01865-18.0022-538X1098-551410.1128/JVI.01865-1830567978https://jvi.asm.org/content/93/6/e01865-18.abstractinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:40:06Zoai:repositorium.sdum.uminho.pt:1822/62296Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:36:50.247512Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model
title A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model
spellingShingle A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model
Keshwara, Rohan
Animals
Antibodies, Neutralizing
Antibodies, Viral
Cell Line
Cercopithecus aethiops
Disease Models, Animal
Female
Glycoproteins
HEK293 Cells
Humans
Marburg Virus Disease
Marburgvirus
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Rabies
Rabies Vaccines
Rabies virus
Vaccination
Vero Cells
Viral Vaccines
ADCC
antibody function
filovirus
immunization
vaccine
Ciências Médicas::Medicina Básica
Science & Technology
title_short A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model
title_full A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model
title_fullStr A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model
title_full_unstemmed A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model
title_sort A recombinant rabies virus expressing the Marburg Virus Glycoprotein Is dependent upon ADCC for protection against Marburg Virus Disease in a Murine Model
author Keshwara, Rohan
author_facet Keshwara, Rohan
Hagen, Katie R.
Abreu-Mota, Tiago
Papaneri, Amy B.
Liu, David
Wirblich, Christoph
Johnson, Reed F.
Schnell, Matthias J.
author_role author
author2 Hagen, Katie R.
Abreu-Mota, Tiago
Papaneri, Amy B.
Liu, David
Wirblich, Christoph
Johnson, Reed F.
Schnell, Matthias J.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Keshwara, Rohan
Hagen, Katie R.
Abreu-Mota, Tiago
Papaneri, Amy B.
Liu, David
Wirblich, Christoph
Johnson, Reed F.
Schnell, Matthias J.
dc.subject.por.fl_str_mv Animals
Antibodies, Neutralizing
Antibodies, Viral
Cell Line
Cercopithecus aethiops
Disease Models, Animal
Female
Glycoproteins
HEK293 Cells
Humans
Marburg Virus Disease
Marburgvirus
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Rabies
Rabies Vaccines
Rabies virus
Vaccination
Vero Cells
Viral Vaccines
ADCC
antibody function
filovirus
immunization
vaccine
Ciências Médicas::Medicina Básica
Science & Technology
topic Animals
Antibodies, Neutralizing
Antibodies, Viral
Cell Line
Cercopithecus aethiops
Disease Models, Animal
Female
Glycoproteins
HEK293 Cells
Humans
Marburg Virus Disease
Marburgvirus
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Rabies
Rabies Vaccines
Rabies virus
Vaccination
Vero Cells
Viral Vaccines
ADCC
antibody function
filovirus
immunization
vaccine
Ciências Médicas::Medicina Básica
Science & Technology
description Accepted Manuscript
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/62296
url http://hdl.handle.net/1822/62296
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Keshwara, R., Hagen, K. R., Abreu-Mota, T., et. al. (2019). A Recombinant Rabies Virus Expressing the Marburg Virus Glycoprotein Is Dependent upon Antibody-Mediated Cellular Cytotoxicity for Protection against Marburg Virus Disease in a Murine Model. Journal of virology, 93(6), e01865-18.
0022-538X
1098-5514
10.1128/JVI.01865-18
30567978
https://jvi.asm.org/content/93/6/e01865-18.abstract
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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