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Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection.
Konrath, Kylie M; Liaw, Kevin; Wu, Yuanhan; Zhu, Xizhou; Walker, Susanne N; Xu, Ziyang; Schultheis, Katherine; Chokkalingam, Neethu; Chawla, Himanshi; Du, Jianqiu; Tursi, Nicholas J; Moore, Alan; Adolf-Bryfogle, Jared; Purwar, Mansi; Reuschel, Emma L; Frase, Drew; Sullivan, Matthew; Fry, Benjamin; Maricic, Igor; Andrade, Viviane M; Iffland, Christel; Crispin, Max; Broderick, Kate E; Humeau, Laurent M P F; Patel, Ami; Smith, Trevor R F; Pallesen, Jesper; Weiner, David B; Kulp, Daniel W.
  • Konrath KM; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Liaw K; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Wu Y; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Zhu X; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Walker SN; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Xu Z; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Schultheis K; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.
  • Chokkalingam N; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Chawla H; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
  • Du J; Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA.
  • Tursi NJ; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Moore A; Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA.
  • Adolf-Bryfogle J; Institute for Protein Innovation, Boston, MA 02115, USA.
  • Purwar M; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Reuschel EL; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Frase D; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Sullivan M; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Fry B; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Maricic I; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.
  • Andrade VM; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.
  • Iffland C; Ligand Pharmaceuticals Inc., San Diego, CA 92121, USA.
  • Crispin M; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
  • Broderick KE; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.
  • Humeau LMPF; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.
  • Patel A; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Smith TRF; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.
  • Pallesen J; Institute for Protein Innovation, Boston, MA 02115, USA.
  • Weiner DB; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • Kulp DW; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dwkulp@wistar.org.
Cell Rep ; 38(5): 110318, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1654152
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanoparticles / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110318

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanoparticles / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110318