https://www.socictopen.socict.org/files/original/aad0359c7037581d2fd4312f5a368b71.pdf 031c1df03105efbca801708e750cfb2f Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Coronavirus Description An account of the resource Dominio científico: Coronavirus Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. Creator An entity primarily responsible for making the resource Jan ter Meulen, Edward N van den Brink, Leo L.M. Poon, Wilfred E. Marissen, Cynthia S W Leung, Freek Cox, Chung Y. Cheung, Arjen Q. Bakker, Johannes A Bogaards, Els van Deventer, Wolfgang Preiser, Hans Wilhelm Doerr, Vincent T Chow, John de Kruif, Joseph S.M. Peiris, Jaap Goudsmit Description An account of the resource BACKGROUND:Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS:Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318-510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. CONCLUSIONS:The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection. Date A point or period of time associated with an event in the lifecycle of the resource 2006 Identifier An unambiguous reference to the resource within a given context DOI: 10.1371/journal.pmed.0030237 Source A related resource from which the described resource is derived PLoS Medicine Publisher An entity responsible for making the resource available Public Library of Science (PLoS) Coverage The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant Medicine Language A language of the resource EN