Key result
An integrated technology platform enabled the isolation of >100 Zika virus-specific human monoclonal antibodies and validation of 29 broadly-neutralizing lead candidates in vivo within 78 days.
Why the study?
The emergence of virulent viral pathogens with pandemic potential requires accelerated antiviral discovery, but long discovery timelines currently limit rapid deployment of human monoclonal antibodies.
The study demonstrates a rapid response platform capable of discovering and validating potent antiviral human monoclonal antibodies against Zika virus in preclinical models within 78 days.
Hypothesis-generating for rapid mAb platforms against Zika; leaves open human translation pending clinical trials.
The emergence and reemergence of highly virulent viral pathogens with pandemic potential has created an urgent need for accelerated discovery of antiviral therapeutics. Antiviral human monoclonal (mAbs) are promising drug candidates to prevent or treat severe viral diseases, but the long timelines needed for discovery limits their rapid deployment and use. Here, we report the development of an integrated sequence of technologies incorporating advances in single-cell mRNA sequence analysis, bioinformatics, synthetic biology, and high-throughput functional analysis that allowed us to discover highly potent antiviral human mAbs and validate their activity in vivo at an unprecedented scale, speed, and efficiency. In a 78-day study, modeling deployment of a rapid response platform to an outbreak, we isolated >100 individual Zika virus (ZIKV) specific human mAbs, assessed their function, identified 29 broadly-neutralizing mAbs, and verified therapeutic potency of lead candidates with antibody-encoding mRNA formulation and/or IgG protein delivery in mice and nonhuman primates. Our work provides a roadmap for the rapid antibody discovery programs against viral pathogens of global concern.
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Gilchuk et al. (2020) studied Zika virus (ZIKV) infection. Integrated technology platform for rapid antibody discovery was evaluated on Discovery and validation of antiviral human mAbs. An integrated technology platform enabled the isolation of >100 Zika virus-specific human monoclonal antibodies and validation of 29 broadly-neutralizing lead candidates in vivo within 78 days.
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