PT - JOURNAL ARTICLE AU - Kylie M. Konrath AU - Kevin Liaw AU - Yuanhan Wu AU - Xizhou Zhu AU - Susanne N. Walker AU - Ziyang Xu AU - Katherine Schultheis AU - Neethu Chokkalingam AU - Jianqiu Du AU - Nicholas J. Tursi AU - Alan Moore AU - Mansi Purwar AU - Emma L. Reuschel AU - Drew Frase AU - Matthew Sullivan AU - Igor Maricic AU - Viviane M. Andrade AU - Christel Iffland AU - Kate E. Broderick AU - Laurent M. P. F. Humeau AU - Trevor R.F. Smith AU - Jesper Pallesen AU - David B. Weiner AU - Daniel W. Kulp TI - Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection AID - 10.1101/2021.04.28.441474 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.04.28.441474 4099 - http://biorxiv.org/content/early/2021/04/28/2021.04.28.441474.short 4100 - http://biorxiv.org/content/early/2021/04/28/2021.04.28.441474.full AB - Antibodies from SARS-CoV-2 vaccines may target epitopes which reduce durability or increase the potential for escape from vaccine-induced immunity. Using a novel synthetic vaccinology pipeline, we developed rationally immune focused SARS-CoV-2 Spike-based vaccines. N-linked glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and comprehensive in vitro screening, we incorporated glycans into the Spike Receptor-Binding Domain (RBD) and assessed antigenic profiles. We developed glycan coated RBD immunogens and engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicited potent neutralizing antibodies in guinea pigs, hamsters and multiple mouse models, including human ACE2 and human B cell repertoire transgenics. RBD nanoparticles encoding wild-type and the P.1 SARS-CoV-2 variant induced high levels of cross-neutralizing antibodies. Single, low dose immunization protected against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of novel, potent coronavirus vaccines.Competing Interest StatementT. Smith, K. Schultheis K.E. Broderick and L. Humeau are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options, from the company. C. Iffland is an employee of Ligand Pharmaceuticals Inc. and as such receives salary and benefits from the company., D.W. Kulp reports a patent for nanoparticle vaccine pending. D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board services. Remuneration received by D.B.W. includes direct payments or stock or stock options, and in the interest of disclosure he notes potential conflicts associated with this work with Inovio and possibly others. In addition, he has a patent DNA vaccine delivery pending to Inovio. No potential conflicts of interest were disclosed by the other authors.