bioRxiv ScienceSearch

Biology subjects

Van Hoeven, N.

Publications and source records attributed to Van Hoeven, N..

2 recordsLinked to original sources

A Thermostable, Flexible RNA Vaccine Delivery Platform for Pandemic Response

Current RNA vaccines against SARS-CoV-2 are limited by instability of both the RNA and the lipid nanoparticle delivery system, requiring storage at -20{degrees}C or -70{degrees}C and compromising universally accessible vaccine distribution. This study demonstrates the thermostability and adaptability of a nanostructured lipid carrier (NLC) RNA vaccine delivery system for use in pandemic preparedness and pandemic response. Liquid NLC is stable at refrigerated temperatures for [≥] 1 year, enabling stockpiling and rapid deployment by point-of-care mixing with any vaccine RNA. Alternatively, NLC complexed with RNA may be readily lyophilized and stored at room temperature for [≥] 8 months or refrigerated temperature for [≥] 21 months. This thermostable RNA vaccine platform could significantly improve distribution of current and future pandemic response vaccines, particularly in low-resource settings. One Sentence SummaryAn RNA vaccine delivery system stable at room temperature for 8+ months and refrigerated for 21+ months.

bioengineering

Integrated technology platform for accelerated discovery of antiviral antibody therapeutics

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.

immunology