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An mRNA SARS-CoV-2 Vaccine Employing Charge-Altering Releasable Transporters with a TLR-9 Agonist Induces Neutralizing Antibodies and T Cell Memory.
Haabeth, Ole A W; Lohmeyer, Julian J K; Sallets, Adrienne; Blake, Timothy R; Sagiv-Barfi, Idit; Czerwinski, Debra K; McCarthy, Blaine; Powell, Abigail E; Wender, Paul A; Waymouth, Robert M; Levy, Ronald.
  • Haabeth OAW; Stanford Cancer Institute, Division of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, United States.
  • Lohmeyer JJK; Stanford Cancer Institute, Division of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, United States.
  • Sallets A; Stanford Cancer Institute, Division of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, United States.
  • Blake TR; Stanford Cancer Institute, Division of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, United States.
  • Sagiv-Barfi I; Department of Chemistry, Stanford University, Stanford, California 94305, United States.
  • Czerwinski DK; Stanford Cancer Institute, Division of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, United States.
  • McCarthy B; Stanford Cancer Institute, Division of Oncology, Department of Medicine, Stanford University, Stanford, California 94305, United States.
  • Powell AE; Department of Chemistry, Stanford University, Stanford, California 94305, United States.
  • Wender PA; Department of Biochemistry & Stanford ChEM-H, Stanford University, Stanford, California 94305, United States.
  • Waymouth RM; Department of Chemistry, Stanford University, Stanford, California 94305, United States.
  • Levy R; Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305, United States.
ACS Cent Sci ; 7(7): 1191-1204, 2021 Jul 28.
Article in English | MEDLINE | ID: covidwho-1387138
Preprint
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ABSTRACT
The SARS-CoV-2 pandemic has necessitated the rapid development of prophylactic vaccines. Two mRNA vaccines have been approved for emergency use by the FDA and have demonstrated extraordinary effectiveness. The success of these mRNA vaccines establishes the speed of development and therapeutic potential of mRNA. These authorized vaccines encode full-length versions of the SARS-CoV-2 spike protein. They are formulated with lipid nanoparticle (LNP) delivery vehicles that have inherent immunostimulatory properties. Different vaccination strategies and alternative mRNA delivery vehicles would be desirable to ensure flexibility of future generations of SARS-CoV-2 vaccines and the development of mRNA vaccines in general. Here, we report on the development of an alternative mRNA vaccine approach using a delivery vehicle called charge-altering releasable transporters (CARTs). Using these inherently nonimmunogenic vehicles, we can tailor the vaccine immunogenicity by inclusion of coformulated adjuvants such as oligodeoxynucleotides with CpG motifs (CpG-ODN). Mice vaccinated with the mRNA-CART vaccine developed therapeutically relevant levels of receptor binding domain (RBD)-specific neutralizing antibodies in both the circulation and in the lung bronchial fluids. In addition, vaccination elicited strong and long-lasting RBD-specific TH1 T cell responses including CD4+ and CD8+ T cell memory.

Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: ACS Cent Sci Year: 2021 Document Type: Article Affiliation country: ACSCENTSCI.1C00361

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: ACS Cent Sci Year: 2021 Document Type: Article Affiliation country: ACSCENTSCI.1C00361