| Autor: |
Addetia A; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, Washington, USA.; Department of Biochemistry, University of Washington, Seattle, Washington, USA., Stewart C; Department of Biochemistry, University of Washington, Seattle, Washington, USA., Seo AJ; Department of Biochemistry, University of Washington, Seattle, Washington, USA., Sprouse KR; Department of Biochemistry, University of Washington, Seattle, Washington, USA.; Howard Hughes Medical Institute, Seattle, WA 98195, USA., Asiri AY; Al-Hayat National Hospital, Riyadh, Saudi Arabia., Al-Mozaini M; Department of Infection and Immunity, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Memish ZA; King Saud Medical City, Ministry of Health, Riyadh, Saudi Arabia.; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.; Kyung Hee University, Seoul, South Korea., Alshukairi A; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.; Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia., Veesler D; Department of Biochemistry, University of Washington, Seattle, Washington, USA.; Howard Hughes Medical Institute, Seattle, WA 98195, USA. |
| Abstrakt: |
Middle-East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Most vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts, however, are limited by a poor understanding of antibody responses elicited by infection along with their durability, fine specificity and contribution of distinct S antigenic sites to neutralization. To address this knowledge gap, we analyzed S-directed binding and neutralizing antibody titers in plasma collected from individuals infected with MERS-CoV in 2017-2019 (prior to the COVID-19 pandemic). We observed that binding and neutralizing antibodies peak 1 to 6 weeks after symptom onset/hospitalization, persist for at least 6 months, and broadly neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S 1 subunit is immunodominant and that antibodies targeting S 1 , particularly the RBD, account for most plasma neutralizing activity. Antigenic site mapping revealed that polyclonal plasma antibodies frequently target RBD epitopes, particularly a site exposed irrespective of the S trimer conformation, whereas targeting of S 2 subunit epitopes is rare, similar to SARS-CoV-2. Our data reveal in unprecedented details the humoral immune responses elicited by MERS-CoV infection, which will guide vaccine and therapeutic design. |
