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dc.contributor.authorVamvaka, Evangelia
dc.contributor.authorFarré Martinez, Gemma
dc.contributor.authorMolinos-Albert, Luis M.
dc.contributor.authorEvans, Abbey
dc.contributor.authorCanela Xandri, Anna
dc.contributor.authorTwyman, Richard M.
dc.contributor.authorCarrillo, Jorge
dc.contributor.authorOrdóñez, Raziel Antonio
dc.contributor.authorShattock, Robin J.
dc.contributor.authorO’Keef, Barry R.
dc.contributor.authorClotet, Bonaventura
dc.contributor.authorBlanco, Julian
dc.contributor.authorKhush, Gurdev S.
dc.contributor.authorChristou, Paul
dc.contributor.authorCapell Capell, Teresa
dc.date.accessioned2019-02-14T11:24:04Z
dc.date.available2019-02-14T11:24:04Z
dc.date.issued2018-08-14
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/10459.1/65736
dc.description.abstractThe transmission of HIV can be prevented by the application of neutralizing monoclonal antibodies and lectins. Traditional recombinant protein manufacturing platforms lack sufficient capacity and are too expensive for developing countries, which suffer the greatest disease burden. Plants offer an inexpensive and scalable alternative manufacturing platform that can produce multiple components in a single plant, which is important because multiple components are required to avoid the rapid emergence of HIV-1 strains resistant to single microbicides. Furthermore, crude extracts can be used directly for prophylaxis to avoid the massive costs of downstream processing and purification. We investigated whether rice could simultaneously produce three functional HIV-neutralizing proteins (the monoclonal antibody 2G12, and the lectins griffithsin and cyanovirin-N). Preliminary in vitro tests showed that the cocktail of three proteins bound to gp120 and achieved HIV-1 neutralization. Remarkably, when we mixed the components with crude extracts of wild-type rice endosperm, we observed enhanced binding to gp120 in vitro and synergistic neutralization when all three components were present. Extracts of transgenic plants expressing all three proteins also showed enhanced in vitro binding to gp120 and synergistic HIV-1 neutralization. Fractionation of the rice extracts suggested that the enhanced gp120 binding was dependent on rice proteins, primarily the globulin fraction. Therefore, the production of HIV-1 microbicides in rice may not only reduce costs compared to traditional platforms but may also provide functional benefits in terms of microbicidal potency.ca_ES
dc.description.sponsorshipWe thank Ms. Jennifer Wilson for technical assistance with live-virus anti-HIV assays. We received funding from Spanish Ministry of Science and Innovation Grant BIO2014-54426-P; Spanish Ministry of Economy, Industry and Competitiveness Grant AGL2017-85377-R; the European Fund for Economic and Regional Development; Generalitat de Catalunya Grant 2017 SGR 828 to the Agricultural Biotechnology and Bioeconomy Unit; and European Union Farma-Factory Grant Agreement 774078, H2020-BB-2016-2017/H2020-BB-2017-1. This project was funded in whole or in part with federal funds from the National Cancer Institute (NCI), NIH, under Contract HHSN26120080001E and was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research, and Instituto de Salud Carlos III project PI14/01307. The EVA648 W61D and gp120 0607 IIIB were provided by the Medical Research Center Centralized Facility for AIDS reagents. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US government.ca_ES
dc.language.isoengca_ES
dc.publisherNational Academy of Sciencesca_ES
dc.relationMINECO/PN2013-2016/BIO2014-54426-Pca_ES
dc.relationMINECO/PN2013-2016/AGL2017-85377-Rca_ES
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1073/pnas.1806022115ca_ES
dc.relation.ispartofPNAS, Proceedings of the National Academy of Sciences of the United States of America, 2018, vol. 115, núm. 33, e7854-7862ca_ES
dc.rightscc-by-nc-nd, (c) Vamvaka et al., 2018ca_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHIV combination microbicidesca_ES
dc.subjectPlant-made pharmaceuticalsca_ES
dc.subjectOryza sativaca_ES
dc.subjectgp120 bindingca_ES
dc.titleUnexpected synergistic HIV neutralization by a triple microbicide produced in rice endospermca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.identifier.idgrec027304
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.1073/pnas.1806022115
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/ 774078/EU/Pharma-Factoryca_ES


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