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Cell Rep . Mapping immunodominant sites on the MERS-CoV spike glycoprotein targeted by infection-elicited antibodies in humans

tetano

Editor, Senior Moderator
Cell Rep


. 2024 Jul 24;43(8):114530.
doi: 10.1016/j.celrep.2024.114530. Online ahead of print. Mapping immunodominant sites on the MERS-CoV spike glycoprotein targeted by infection-elicited antibodies in humans

Amin Addetia[SUP] 1 [/SUP], Cameron Stewart[SUP] 2 [/SUP], Albert J Seo[SUP] 2 [/SUP], Kaitlin R Sprouse[SUP] 3 [/SUP], Ayed Y Asiri[SUP] 4 [/SUP], Maha Al-Mozaini[SUP] 5 [/SUP], Ziad A Memish[SUP] 6 [/SUP], Abeer N Alshukairi[SUP] 7 [/SUP], David Veesler[SUP] 8 [/SUP]



Affiliations
Free article Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts are limited by a poor understanding of antibody responses elicited by infection. Here, we analyze S-directed antibody responses in plasma collected from MERS-CoV-infected individuals. We observe that binding and neutralizing antibodies peak 1-6 weeks after symptom onset/hospitalization, persist for at least 6 months, and neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S[SUB]1[/SUB] subunit is immunodominant and that antibodies targeting S[SUB]1[/SUB], particularly the receptor-binding domain (RBD), account for most plasma neutralizing activity. Antigenic site mapping reveals that plasma antibodies frequently target RBD epitopes, whereas targeting of S[SUB]2[/SUB] subunit epitopes is rare. Our data reveal the humoral immune responses elicited by MERS-CoV infection, which will guide vaccine and therapeutic design.

Keywords: CP: Immunology; MERS-CoV; antibody; binding; epitopes; merbecovirus; neutralization; plasma; spike; therapeutic; vaccine.

 
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