Details

Autor(en) / Beteiligte

• Hsieh, Ching-Lin
• Werner, Anne P.
• Leist, Sarah R.
• Stevens, Laura J.
• Falconer, Ester
• Goldsmith, Jory A.
• Chou, Chia-Wei
• Abiona, Olubukola M.
• West, Ande
• Westendorf, Kathryn
• Muthuraman, Krithika
• Fritch, Ethan J.
• Dinnon, Kenneth H.
• Schäfer, Alexandra
• Denison, Mark R.
• Chappell, James D.
• Baric, Ralph S.
• Graham, Barney S.
• Corbett, Kizzmekia S.
• McLellan, Jason S.

Titel

Stabilized coronavirus spike stem elicits a broadly protective antibody

Ist Teil von

• Cell reports (Cambridge), 2021-11, Vol.37 (5), p.109929-109929, Article 109929

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive β-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies. [Display omitted] •Structure-guided design generates MERS-CoV spike stabilized stem (SS) antigens•Cross-reactive CoV-spike-stem-specific monoclonal antibodies•Structures of the Fab22-spike complexes reveal a conserved, protective epitope•Passive transfer of IgG22 protects mice against MERS-CoV and SARS-CoV-2 challenge Hsieh et al. generate MERS-CoV spike stabilized stem (SS) antigens using a structure-guided approach. Mice immunized with MERS SS are protected against MERS-CoV challenge and used for isolation of cross-reactive monoclonal antibodies, including IgG22, which protects mice against MERS-CoV and SARS-CoV-2 challenges. Structures of Fab22-spike complexes reveal a conserved epitope.