Efficient development of fully human monoclonal antibodies by rapid mRNA immunization of humanized mice followed by single B cell sequencing

Published: 17 November 2022| Version 1 | DOI: 10.17632/4dcgs8mvzx.1
Contributors:
Ping REN,
Peng Lei,
Luojia Yang,
Kazushi Suzuki,
Zhenhao Fang,
Paul Renauer,
Qianqian Lin,
Meizhu Bai,
Tongqing Li,
Paul Clark,
Deryl Klein,
Sidi Chen

Description

As a clinical vaccine, lipid nanoparticle (LNP) mRNA demonstrated potent and broad antibody responses, leading to speculation about its potential for antibody discovery. Here, we developed RAMIHM, a highly efficient strategy for developing fully human monoclonal antibodies that employs rapid mRNA immunization of humanized mice followed by single B cell sequencing (scBCR-seq). We immunized humanized transgenic mice with RAMIHM and generated 15 top-ranked clones from peripheral blood, plasma B, and memory B cell populations, demonstrating a high rate of antigen-specificity (93.3%). Two Omicron-specific neutralizing antibodies with high potent and one broad-spectrum neutralizing antibody were discovered. Furthermore, we extended the application of RAMIHM to cancer immunotherapy targets, including a single transmembrane protein CD22 and a multi-transmembrane GPCR target, GPRC5D, which is difficult for traditional protein immunization methods. RAMIHM-scBCR-seq is a broadly applicable platform for the rapid and efficient development of fully human monoclonal antibodies against an assortment of targets.

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Institutions

Yale University Yale Cancer Center

Categories

Flow Cytometry

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