Stabilization of a Broadly Neutralizing Anti-Chikungunya Virus Single Domain Antibody

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dc.contributor.authorLiu, Jinny L.en
dc.contributor.authorWebb, Emily M.en
dc.contributor.authorZabetakis, Danen
dc.contributor.authorBurke, Crystal W.en
dc.contributor.authorGardner, Christina L.en
dc.contributor.authorGlass, Pamela J.en
dc.contributor.authorLegler, Patricia M.en
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.contributor.authorAnderson, George P.en
dc.contributor.authorGoldman, Ellen R.en
dc.date.accessioned2021-05-28T14:40:59Zen
dc.date.available2021-05-28T14:40:59Zen
dc.date.issued2021-01-28en
dc.description.abstractA single domain antibody (clone CC3) previously found to neutralize a vaccine strain of the chikungunya virus (PRNT50 = 2. 5 ng/mL) was found to be broadly neutralizing. Clone CC3 is not only able to neutralize a wild-type (WT) strain of chikungunya virus (CHIKV), but also neutralizes WT strains of Mayaro virus (MAYV) and Ross River virus (RRV); both arthralgic, Old World alphaviruses. Interestingly, CC3 also demonstrated a degree of neutralizing activity against the New World alphavirus, Venezuelan equine encephalitis virus (VEEV); albeit both the vaccine strain, TC-83, and the parental, WT Trinidad donkey strain had PRNT50 values similar to 1,000-fold higher than that of CHIKV. However, no neutralization activity was observed with Western equine encephalitis virus (WEEV). Ten CC3 variants designed to possess a range of isoelectric points, both higher and lower, were constructed. This approach successfully identified several lower pI mutants which possessed improved thermal stabilities by as much as 10 degrees C over the original CC3 (T-m = 62 degrees C), and excellent refolding abilities while maintaining their capacity to bind and neutralize CHIKV.en
dc.description.notesThe research conducted at NRL and USAMRIID was supported by the Defense Threat Reduction Agency (DTRA) project CB10487. The research conducted at USAMRIID was performed while CG held an NRC Research Associateship award in PG lab. The opinions, interpretations, conclusions, and recommendations are those of the author and are not not necessarily endorsed by the U.S. Army or the US Navy. The research conducted at VT was performed while EW held a doctoral fellowship through the Institute for Critical Technology and Applied Science (ICTAS).en
dc.description.sponsorshipDefense Threat Reduction Agency (DTRA)United States Department of DefenseDefense Threat Reduction Agency [CB10487]; Institute for Critical Technology and Applied Science (ICTAS); NRCNational Research Centre (NRC)en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fmed.2021.626028en
dc.identifier.eissn2296-858Xen
dc.identifier.other626028en
dc.identifier.pmid33585527en
dc.identifier.urihttp://hdl.handle.net/10919/103547en
dc.identifier.volume8en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectchikungunya virusen
dc.subjectold worlden
dc.subjectnew worlden
dc.subjectalphavirusen
dc.subjectneutralizationen
dc.subjectmelting temperatureen
dc.subjectsingle domain antibodyen
dc.titleStabilization of a Broadly Neutralizing Anti-Chikungunya Virus Single Domain Antibodyen
dc.title.serialFrontiers in Medicineen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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