Safety and tolerability of the adeno‐associated virus vector, aav6.2ff, expressing a monoclonal antibody in murine and ovine animal models

Amira D. Rghei, Laura P. van Lieshout, Benjamin M. McLeod, Yanlong Pei, Jordyn A. Lopes, Nicole Zielinska, Enzo M. Baracuhy, Brenna A.Y. Stevens, Sylvia P. Thomas, Jacob G.E. Yates, Bryce M. Warner, Darwyn Kobasa, Hugues Fausther‐bovendo, Gary P. Kobinger, Khalil Karimi, Brad Thompson, Byram W. Bridle, Leonardo Susta, Sarah K. Wootton

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Adeno‐associated virus (AAV) vector mediated expression of therapeutic monoclonal antibodies is an alternative strategy to traditional vaccination to generate immunity in immunosup-pressed or immunosenescent individuals. In this study, we vectorized a human monoclonal antibody (31C2) directed against the spike protein of SARS‐CoV‐2 and determined the safety profile of this AAV vector in mice and sheep as a large animal model. In both studies, plasma biochemical parameters and hematology were comparable to untreated controls. Except for mild myositis at the site of injection, none of the major organs revealed any signs of toxicity. AAV‐mediated human IgG expression increased steadily throughout the 28‐day study in sheep, resulting in peak concentrations of 21.4–46.7 μg/ mL, demonstrating practical scale up from rodent to large animal models. This alternative approach to immunity is worth further exploration after this demonstration of safety, tolerability, and scalability in a large animal model.

Original languageEnglish (US)
Article number1186
JournalBiomedicines
Volume9
Issue number9
DOIs
StatePublished - Sep 2021
Externally publishedYes

Keywords

  • Adeno‐associated virus (AAV) vector
  • Large animal model
  • Monoclonal antibody
  • Safety
  • Tolerability
  • Vectored immunoprophylaxis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology

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