Antibody engineering improves neutralization activity against K417 spike mutant SARS-CoV-2 variants

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Neutralizing antibodies are crucial for treating COVID-19.
• Mutations in SARS-CoV-2 variants can diminish antibody efficacy.
• Development of new monoclonal antibodies (mAbs) and engineering strategies are vital.

Purpose of the Study:

• To identify novel neutralizing antibodies against SARS-CoV-2.
• To characterize and engineer antibodies for improved efficacy against SARS-CoV-2 variants.
• To understand the structural basis of antibody-variant interactions.

Main Methods:

• Phage display antibody library screening from COVID-19 patients.
• In vitro and in vivo characterization of antibody clones.
• Crystal structural analysis to elucidate binding mechanisms.
• Antibody engineering to enhance neutralizing activity.

Main Results:

• Identified R3P1-E4 mAb with potent SARS-CoV-2 neutralizing activity.
• R3P1-E4 suppressed infection and rescued lethal phenotypes in a mouse model.
• Structural analysis revealed reduced activity against K417 mutations.
• Engineered antibodies demonstrated improved neutralization against SARS-CoV-2 variants with K417 mutations.

Conclusions:

• A strategy for identifying and engineering neutralizing antibodies against SARS-CoV-2 variants was established.
• The R3P1-E4 antibody and its engineered forms represent potential therapeutic candidates.
• Understanding structural interactions is key to overcoming viral mutations.