{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:26:56Z","timestamp":1778941616656,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["AGL2017-83226R"],"award-info":[{"award-number":["AGL2017-83226R"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["AGL-2011-22485"],"award-info":[{"award-number":["AGL-2011-22485"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["S2013\/ABI-2906"],"award-info":[{"award-number":["S2013\/ABI-2906"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010774","name":"Consejer\u00eda de Educaci\u00f3n e Investigaci\u00f3n","doi-asserted-by":"publisher","award":["S2018\/BAA-4370"],"award-info":[{"award-number":["S2018\/BAA-4370"]}],"id":[{"id":"10.13039\/501100010774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>In vitro neutralizing antibodies have been often correlated with protection against Rift Valley fever virus (RVFV) infection. We have reported previously that a single inoculation of sucrose-purified modified vaccinia Ankara (MVA) encoding RVFV glycoproteins (rMVAGnGc) was sufficient to induce a protective immune response in mice after a lethal RVFV challenge. Protection was related to the presence of glycoprotein specific CD8+ cells, with a low-level detection of in vitro neutralizing antibodies. In this work we extended those observations aimed to explore the role of humoral responses after MVA vaccination and to study the contribution of each glycoprotein antigen to the protective efficacy. Thus, we tested the efficacy and immune responses in BALB\/c mice of recombinant MVA viruses expressing either glycoprotein Gn (rMVAGn) or Gc (rMVAGc). In the absence of serum neutralizing antibodies, our data strongly suggest that protection of vaccinated mice upon the RVFV challenge can be achieved by the activation of cellular responses mainly directed against Gc epitopes. The involvement of cellular immunity was stressed by the fact that protection of mice was strain dependent. Furthermore, our data suggest that the rMVA based single dose vaccination elicits suboptimal humoral immune responses against Gn antigen since disease in mice was exacerbated upon virus challenge in the presence of rMVAGnGc or rMVAGn immune serum. Thus, Gc-specific cellular immunity could be an important component in the protection after the challenge observed in BALB\/c mice, contributing to the elimination of infected cells reducing morbidity and mortality and counteracting the deleterious effect of a subneutralizing antibody immune response.<\/jats:p>","DOI":"10.3390\/vaccines8010082","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T10:09:57Z","timestamp":1581674997000},"page":"82","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["MVA Vectored Vaccines Encoding Rift Valley Fever Virus Glycoproteins Protect Mice against Lethal Challenge in the Absence of Neutralizing Antibody Responses"],"prefix":"10.3390","volume":"8","author":[{"given":"Elena","family":"L\u00f3pez-Gil","sequence":"first","affiliation":[{"name":"Animal Health Research Centre (CISA), National Institute for Agriculture and Food Research and Technology (INIA), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-7277","authenticated-orcid":false,"given":"Sandra","family":"Moreno","sequence":"additional","affiliation":[{"name":"Animal Health Research Centre (CISA), National Institute for Agriculture and Food Research and Technology (INIA), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0801-9166","authenticated-orcid":false,"given":"Javier","family":"Ortego","sequence":"additional","affiliation":[{"name":"Animal Health Research Centre (CISA), National Institute for Agriculture and Food Research and Technology (INIA), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"Borrego","sequence":"additional","affiliation":[{"name":"Animal Health Research Centre (CISA), National Institute for Agriculture and Food Research and Technology (INIA), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gema","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Animal Health Research Centre (CISA), National Institute for Agriculture and Food Research and Technology (INIA), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-538X","authenticated-orcid":false,"given":"Alejandro","family":"Brun","sequence":"additional","affiliation":[{"name":"Animal Health Research Centre (CISA), National Institute for Agriculture and Food Research and Technology (INIA), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1051\/vetres\/2010033","article-title":"Rift Valley fever virus (Bunyaviridae: Phlebovirus): An update on pathogenesis, molecular epidemiology, vectors, diagnostics and prevention","volume":"41","author":"Pepin","year":"2010","journal-title":"Vet. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19506","DOI":"10.2807\/ese.15.10.19506-en","article-title":"Rift Valley fever--a threat for Europe?","volume":"15","author":"Chevalier","year":"2010","journal-title":"Euro. Surveill."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Napp, S., Chevalier, V., Busquets, N., Calistri, P., Casal, J., Attia, M., Elbassal, R., Hosni, H., Farrag, H., and Hassan, N. (2018). Understanding the legal trade of cattle and camels and the derived risk of Rift Valley Fever introduction into and transmission within Egypt. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006143"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1089\/vbz.2008.0009","article-title":"Potential vectors of Rift Valley fever virus in the Mediterranean region","volume":"8","author":"Moutailler","year":"2008","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2174\/156652311795684731","article-title":"MVA and NYVAC as vaccines against emergent infectious diseases and cancer","volume":"11","author":"Gomez","year":"2011","journal-title":"Curr. Gene Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4247","DOI":"10.1016\/j.vaccine.2013.03.021","article-title":"Recombinant MVA vaccines: Dispelling the myths","volume":"31","author":"Cottingham","year":"2013","journal-title":"Vaccine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1586\/14760584.2013.845531","article-title":"Clinical applications of attenuated MVA poxvirus strain","volume":"12","author":"Gomez","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"ref_8","first-page":"464","article-title":"Modified vaccinia virus ankara (MVA)--development as recombinant vaccine and prospects for use in veterinary medicine","volume":"128","author":"Volz","year":"2015","journal-title":"Berl. Munch. Tierarztl. Wochenschr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.coviro.2012.02.017","article-title":"Breaking the chain: Rift Valley fever virus control via livestock vaccination","volume":"2","author":"Bird","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF01309641","article-title":"The synergistic neutralization of Rift Valley fever virus by monoclonal antibodies to the envelope glycoproteins","volume":"125","author":"Besselaar","year":"1992","journal-title":"Arch. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0923-2516(07)80002-1","article-title":"The effect of neutralizing monoclonal antibodies on early events in Rift Valley fever virus infectivity","volume":"145","author":"Besselaar","year":"1994","journal-title":"Res. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/0923-2516(91)90069-F","article-title":"Antigenic analysis of Rift Valley fever virus isolates: Monoclonal antibodies distinguish between wild-type and neurotropic virus strains","volume":"142","author":"Besselaar","year":"1991","journal-title":"Res. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1128\/jvi.64.4.1549-1555.1990","article-title":"Expression strategy of a phlebovirus: Biogenesis of proteins from the Rift Valley fever virus M segment","volume":"64","author":"Suzich","year":"1990","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.antiviral.2012.06.001","article-title":"Molecular biology and genetic diversity of Rift Valley fever virus","volume":"95","author":"Ikegami","year":"2012","journal-title":"Antiviral Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41467-017-02789-2","article-title":"Shielding and activation of a viral membrane fusion protein","volume":"9","author":"Halldorsson","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1016\/j.celrep.2018.12.001","article-title":"A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus","volume":"25","author":"Allen","year":"2018","journal-title":"Cell Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lopez-Gil, E., Lorenzo, G., Hevia, E., Borrego, B., Eiden, M., Groschup, M., Gilbert, S.C., and Brun, A. (2013). 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. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002309"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13567-018-0516-z","article-title":"Efficacy of different DNA and MVA prime-boost vaccination regimens against a Rift Valley fever virus (RVFV) challenge in sheep 12 weeks following vaccination","volume":"49","author":"Lorenzo","year":"2018","journal-title":"Vet. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/1743-422X-10-349","article-title":"Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice","volume":"10","author":"Warimwe","year":"2013","journal-title":"Virol. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20617","DOI":"10.1038\/srep20617","article-title":"Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever","volume":"6","author":"Warimwe","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1016\/S1286-4579(00)01323-X","article-title":"Vaccinia expression of Mycobacterium tuberculosis-secreted proteins: Tissue plasminogen activator signal sequence enhances expression and immunogenicity of M. tuberculosis Ag85","volume":"2","author":"Malin","year":"2000","journal-title":"Microbes Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00705-013-1867-4","article-title":"Generation and application of monoclonal antibodies against Rift Valley fever virus nucleocapsid protein NP and glycoproteins Gn and Gc","volume":"159","author":"Jackel","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1089\/vbz.2009.0205","article-title":"Experimental infection of young adult European breed sheep with Rift Valley fever virus field isolates","volume":"10","author":"Busquets","year":"2010","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1016\/j.vaccine.2010.02.018","article-title":"Protection against lethal Rift Valley fever virus (RVFV) infection in transgenic IFNAR(-\/-) mice induced by different DNA vaccination regimens","volume":"28","author":"Lorenzo","year":"2010","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.antiviral.2014.05.020","article-title":"Efficacy assessment of an MVA vectored Rift Valley Fever vaccine in lambs","volume":"108","author":"Busquets","year":"2014","journal-title":"Antiviral Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1016\/j.vaccine.2009.12.062","article-title":"Rift Valley fever virus subunit vaccines confer complete protection against a lethal virus challenge","volume":"28","author":"Kortekaas","year":"2010","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1016\/j.vaccine.2007.12.028","article-title":"Traitors of the immune system-enhancing antibodies in HIV infection: Their possible implication in HIV vaccine development","volume":"26","author":"Beck","year":"2008","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1292\/jvms.60.49","article-title":"Antibody-dependent enhancement of feline infectious peritonitis virus infection in feline alveolar macrophages and human monocyte cell line U937 by serum of cats experimentally or naturally infected with feline coronavirus","volume":"60","author":"Hohdatsu","year":"1998","journal-title":"J. Vet. Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7539","DOI":"10.1128\/JVI.77.13.7539-7544.2003","article-title":"Antibody-dependent enhancement of Ebola virus infection","volume":"77","author":"Takada","year":"2003","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/rmv.405","article-title":"Antibody-dependent enhancement of viral infection: Molecular mechanisms and in vivo implications","volume":"13","author":"Takada","year":"2003","journal-title":"Rev. Med. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1089\/088282403763635465","article-title":"Antibody-dependent enhancement of virus infection and disease","volume":"16","author":"Tirado","year":"2003","journal-title":"Viral Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bbrc.2014.07.090","article-title":"Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins","volume":"451","author":"Wang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.4049\/jimmunol.1301410","article-title":"Complement component C5 recruits neutrophils in the absence of C3 during respiratory infection with modified vaccinia virus Ankara","volume":"194","author":"Price","year":"2015","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1006\/viro.1998.9289","article-title":"Complement can neutralize HIV-1 plasma virus by a C5-independent mechanism","volume":"248","author":"Sullivan","year":"1998","journal-title":"Virology"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/82\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:57:10Z","timestamp":1760173030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/82"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,12]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["vaccines8010082"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8010082","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,12]]}}}