RT Journal Article
SR Electronic
T1 Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.28.441474
DO 10.1101/2021.04.28.441474
A1 Kylie M. Konrath
A1 Kevin Liaw
A1 Yuanhan Wu
A1 Xizhou Zhu
A1 Susanne N. Walker
A1 Ziyang Xu
A1 Katherine Schultheis
A1 Neethu Chokkalingam
A1 Jianqiu Du
A1 Nicholas J. Tursi
A1 Alan Moore
A1 Mansi Purwar
A1 Emma L. Reuschel
A1 Drew Frase
A1 Matthew Sullivan
A1 Igor Maricic
A1 Viviane M. Andrade
A1 Christel Iffland
A1 Kate E. Broderick
A1 Laurent M. P. F. Humeau
A1 Trevor R.F. Smith
A1 Jesper Pallesen
A1 David B. Weiner
A1 Daniel W. Kulp
YR 2021
UL http://biorxiv.org/content/early/2021/04/28/2021.04.28.441474.abstract
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.