Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever

Detalhes bibliográficos
Autor(a) principal: Abreu-Mota, Tiago
Data de Publicação: 2018
Outros Autores: Hagen, Katie R., Cooper, Kurt, Jahrling, Peter B., Tan, Gene, 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/1822/58718
Resumo: Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.
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spelling Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever3T3 CellsAnimalsAntibodies, NeutralizingAntibodies, ViralAntibody-Dependent Cell CytotoxicityCell MembraneGenetic VectorsGlucosidesGlycoproteinsGuinea PigsImmunity, HumoralImmunizationImmunoglobulin GLassa FeverLassa virusLipid AMacrophagesMiceMice, Inbred C57BLRabies VaccinesReceptors, IgGVaccines, SyntheticVirionVirulenceCiências Médicas::Medicina BásicaScience & TechnologyLassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.NIH grants R01 AI105204 to M.J.S., by the Jefferson Vaccine Center, and by the Fundação para a Ciência e Tecnologia (FCT) scholarship PD/BD/105847/2014 (to T.A.-M.). This work was also funded in part through the NIAID Division of Intramural Research and the NIAID Division of Clinical Research, Battelle Memorial Institute’s prime contract with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016Iinfo:eu-repo/semantics/publishedVersionNature ResearchUniversidade do MinhoAbreu-Mota, TiagoHagen, Katie R.Cooper, KurtJahrling, Peter B.Tan, GeneWirblich, ChristophJohnson, Reed F.Schnell, Matthias J.2018-102018-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/58718engAbreu-Mota, T., Hagen, K. R., Cooper, K., Jahrling, P. B., Tan, G., Wirblich, C., ... & Schnell, M. J. (2018). Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever. Nature communications, 9(1), 42232041-17232041-172310.1038/s41467-018-06741-w30310067https://www.nature.com/articles/s41467-018-06741-w?campaign_url=https%3A%2F%2Fhospitals.jefferson.edu%2Fnews%2F2018%2F10%2FLassa-fever-virus-vaccine-and-new-test-for-immunity.htmlinfo: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:RCAAP2023-07-21T12:20:09Zoai:repositorium.sdum.uminho.pt:1822/58718Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:13:14.008310Repositório 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 Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
title Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
spellingShingle Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
Abreu-Mota, Tiago
3T3 Cells
Animals
Antibodies, Neutralizing
Antibodies, Viral
Antibody-Dependent Cell Cytotoxicity
Cell Membrane
Genetic Vectors
Glucosides
Glycoproteins
Guinea Pigs
Immunity, Humoral
Immunization
Immunoglobulin G
Lassa Fever
Lassa virus
Lipid A
Macrophages
Mice
Mice, Inbred C57BL
Rabies Vaccines
Receptors, IgG
Vaccines, Synthetic
Virion
Virulence
Ciências Médicas::Medicina Básica
Science & Technology
title_short Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
title_full Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
title_fullStr Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
title_full_unstemmed Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
title_sort Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever
author Abreu-Mota, Tiago
author_facet Abreu-Mota, Tiago
Hagen, Katie R.
Cooper, Kurt
Jahrling, Peter B.
Tan, Gene
Wirblich, Christoph
Johnson, Reed F.
Schnell, Matthias J.
author_role author
author2 Hagen, Katie R.
Cooper, Kurt
Jahrling, Peter B.
Tan, Gene
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 Abreu-Mota, Tiago
Hagen, Katie R.
Cooper, Kurt
Jahrling, Peter B.
Tan, Gene
Wirblich, Christoph
Johnson, Reed F.
Schnell, Matthias J.
dc.subject.por.fl_str_mv 3T3 Cells
Animals
Antibodies, Neutralizing
Antibodies, Viral
Antibody-Dependent Cell Cytotoxicity
Cell Membrane
Genetic Vectors
Glucosides
Glycoproteins
Guinea Pigs
Immunity, Humoral
Immunization
Immunoglobulin G
Lassa Fever
Lassa virus
Lipid A
Macrophages
Mice
Mice, Inbred C57BL
Rabies Vaccines
Receptors, IgG
Vaccines, Synthetic
Virion
Virulence
Ciências Médicas::Medicina Básica
Science & Technology
topic 3T3 Cells
Animals
Antibodies, Neutralizing
Antibodies, Viral
Antibody-Dependent Cell Cytotoxicity
Cell Membrane
Genetic Vectors
Glucosides
Glycoproteins
Guinea Pigs
Immunity, Humoral
Immunization
Immunoglobulin G
Lassa Fever
Lassa virus
Lipid A
Macrophages
Mice
Mice, Inbred C57BL
Rabies Vaccines
Receptors, IgG
Vaccines, Synthetic
Virion
Virulence
Ciências Médicas::Medicina Básica
Science & Technology
description Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
2018-10-01T00:00:00Z
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/1822/58718
url http://hdl.handle.net/1822/58718
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Abreu-Mota, T., Hagen, K. R., Cooper, K., Jahrling, P. B., Tan, G., Wirblich, C., ... & Schnell, M. J. (2018). Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever. Nature communications, 9(1), 4223
2041-1723
2041-1723
10.1038/s41467-018-06741-w
30310067
https://www.nature.com/articles/s41467-018-06741-w?campaign_url=https%3A%2F%2Fhospitals.jefferson.edu%2Fnews%2F2018%2F10%2FLassa-fever-virus-vaccine-and-new-test-for-immunity.html
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 Nature Research
publisher.none.fl_str_mv Nature Research
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
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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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