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dc.contributor.authorVlahava, Virginia-Maria
dc.contributor.authorMurrel, Isa
dc.contributor.authorZhuang, Lihui
dc.contributor.authorAicheler, Rebecca
dc.contributor.authorLim, Eleanor
dc.contributor.authorMiners, Kelly L.
dc.contributor.authorLadell, Kristin
dc.contributor.authorSuárez, Nicolás M.
dc.contributor.authorPrice, David A.
dc.contributor.authorDavison, Andrew J.
dc.contributor.authorWilkinson, Gavin W.G
dc.contributor.authorWills, Mark R.
dc.contributor.authorWeekes, Michael P.
dc.contributor.authorWang, Eddie C.Y.
dc.contributor.authorStanton, Richard J.
dc.date.accessioned2021-02-19T11:47:42Z
dc.date.available2021-02-19T11:47:42Z
dc.date.issued2021-02-15
dc.identifier.citationVlahava, V.M., Murrell, I., Zhuang, L., Aicheler, R.J., Lim, E., Miners, K.L., Ladell, K., Suárez, N.M., Price, D.A., Davison, A.J., Wilkinson, G.W., Wills, M.R., Weekes, M.P., Wang, E.C., Stanton, R.J.(2021) 'Monoclonal antibodies targeting nonstructural viral antigens can activate ADCC against human cytomegalovirus', The Journal of Clinical Investigation, 131(4) doi: 10.1172/JCI139296
dc.identifier.issn0021-9738
dc.identifier.issn1558-8238 (electronic)
dc.identifier.urihttp://hdl.handle.net/10369/11317
dc.descriptionArticle published in Journal of Clinical Investigation available open access at https://doi.org/10.1172/JCI139296en_US
dc.description.abstractHuman cytomegalovirus (HCMV) is a ubiquitous pathogen that causes severe disease following congenital infection and in immunocompromised individuals. No vaccines are licensed, and there are limited treatment options. We now show that the addition of anti-HCMV antibodies (Abs) can activate NK cells prior to the production of new virions, through Ab-dependent cellular cytotoxicity (ADCC), overcoming viral immune evasins. Quantitative proteomics defined the most abundant HCMV proteins on the cell surface, and we screened these targets to identify the viral antigens responsible for activating ADCC. Surprisingly, these were not structural glycoproteins; instead, the immune evasins US28, RL11, UL5, UL141, and UL16 each individually primed ADCC. We isolated human monoclonal Abs (mAbs) specific for UL16 or UL141 from a seropositive donor and optimized them for ADCC. Cloned Abs targeting a single antigen (UL141) were sufficient to mediate ADCC against HCMV-infected cells, even at low concentrations. Collectively, these findings validated an unbiased methodological approach to the identification of immunodominant viral antigens, providing a pathway toward an immunotherapeutic strategy against HCMV and potentially other pathogens.en_US
dc.description.sponsorshipThis work was supported by funding from the Wellcome Trust (100326/Z/12/Z, 204870/Z/16/Z, 108070/Z/15/Z) and the Medical Research Council (MRC) (MR/S00971X/1, MR/L008734/1, MR/P001602/1, MC_UU_12014/3, MR/S00081X/1. LZ was funded by a grant from Kymab, however, Kymab had no part in the design, execution, or analysis of the experiments reported in this study.en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.ispartofseriesJournal of Clinical Investigation;
dc.titleMonoclonal antibodies targeting nonstructural viral antigens can activate ADCC against human cytomegalovirusen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1172/JCI139296
dcterms.dateAccepted2020-09-16
rioxxterms.versionVoRen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/en_US
rioxxterms.licenseref.startdate2021-02-19


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