1. Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection.
- Author
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Konrath KM, Liaw K, Wu Y, Zhu X, Walker SN, Xu Z, Schultheis K, Chokkalingam N, Chawla H, Du J, Tursi NJ, Moore A, Adolf-Bryfogle J, Purwar M, Reuschel EL, Frase D, Sullivan M, Fry B, Maricic I, Andrade VM, Iffland C, Crispin M, Broderick KE, Humeau LMPF, Patel A, Smith TRF, Pallesen J, Weiner DB, and Kulp DW
- Subjects
- Animals, Antibodies, Neutralizing immunology, Binding Sites, COVID-19 Vaccines chemistry, COVID-19 Vaccines genetics, Cricetinae, Epitopes, Guinea Pigs, Immunogenicity, Vaccine, Mice, Nanoparticles chemistry, Nucleic Acid-Based Vaccines administration & dosage, Nucleic Acid-Based Vaccines chemistry, Nucleic Acid-Based Vaccines genetics, Nucleic Acid-Based Vaccines immunology, Polysaccharides chemistry, Polysaccharides genetics, Polysaccharides immunology, SARS-CoV-2 chemistry, SARS-CoV-2 genetics, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus immunology, Vaccine Potency, COVID-19 prevention & control, COVID-19 Vaccines administration & dosage, COVID-19 Vaccines immunology, Nanoparticles administration & dosage, SARS-CoV-2 immunology
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines., Competing Interests: Declaration of interests T.R.F.S., K.S., K.E.B., and L.M.P.F.H. are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options, from the company. C.I. is an employee of Ligand Pharmaceuticals, Inc. and as such receives salary and benefits from the company. D.W.K. 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 Pharmaceuticals and possibly others. In addition, he has a patent DNA vaccine delivery pending to Inovio Pharmaceuticals. The other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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