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bioRxiv · 10.1101/2022.03.17.484817

Potent and specific human monoclonal antibodies against SARS-CoV-2 Omicron variant by rapid mRNA immunization of humanized mice

Ren, P.·Peng, L.·Fang, Z.·Suzuki, K.·Renauer, P. A.·Lin, Q.·Bai, M.·Yang, L.·Li, T.·Clark, P.·Klein, D.·Chen, S.
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Abstract

The Omicron variant (B.1.1.529) of SARS-CoV-2 rapidly becomes dominant globally. Its extensive mutations confer severe efficacy reduction to most of existing antibodies or vaccines. Here, we developed RAMIHM, a highly efficient strategy to generate fully human monoclonal antibodies (mAbs), directly applied it with Omicron-mRNA immunization, and isolated three potent and specific clones against Omicron. Rapid mRNA immunization elicited strong anti-Omicron antibody response in humanized mice, along with broader anti-coronavirus activity. Customized single cell BCR sequencing mapped the clonal repertoires. Top-ranked clones collectively from peripheral blood, plasma B and memory B cell populations showed high rate of Omicron-specificity (93.3%) from RAMIHM-scBCRseq. Clone-screening identified three highly potent neutralizing antibodies that have low nanomolar affinity for Omicron RBD, and low ng/mL level IC50 in neutralization, more potent than majority of currently approved or authorized clinical RBD-targeting mAbs. These lead mAbs are fully human and ready for downstream IND-enabling and/or translational studies.

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Ren, P., Peng, L., Fang, Z., Suzuki, K., Renauer, P. A., Lin, Q., Bai, M., Yang, L., Li, T., Clark, P., Klein, D., Chen, S.. 2022-03-18. Potent and specific human monoclonal antibodies against SARS-CoV-2 Omicron variant by rapid mRNA immunization of humanized mice. https://doi.org/10.1101/2022.03.17.484817

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