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

doi:10.3390/biomedicines9091186

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 journal › Article › peer-review

8 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 language	English (US)
Article number	1186
Journal	Biomedicines
Volume	9
Issue number	9
DOIs	https://doi.org/10.3390/biomedicines9091186
State	Published - Sep 2021
Externally published	Yes

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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10.3390/biomedicines9091186

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Rghei, A. D., van Lieshout, L. P., McLeod, B. M., Pei, Y., Lopes, J. A., Zielinska, N., Baracuhy, E. M., Stevens, B. A. Y., Thomas, S. P., Yates, J. G. E., Warner, B. M., Kobasa, D., Fausther‐bovendo, H., Kobinger, G. P., Karimi, K., Thompson, B., Bridle, B. W., Susta, L., & Wootton, S. K. (2021). Safety and tolerability of the adeno‐associated virus vector, aav6.2ff, expressing a monoclonal antibody in murine and ovine animal models. Biomedicines, 9(9), Article 1186. https://doi.org/10.3390/biomedicines9091186

Rghei, AD, van Lieshout, LP, McLeod, BM, Pei, Y, Lopes, JA, Zielinska, N, Baracuhy, EM, Stevens, BAY, Thomas, SP, Yates, JGE, Warner, BM, Kobasa, D, Fausther‐bovendo, H , Kobinger, GP, Karimi, K, Thompson, B, Bridle, BW, Susta, L & Wootton, SK 2021, 'Safety and tolerability of the adeno‐associated virus vector, aav6.2ff, expressing a monoclonal antibody in murine and ovine animal models', Biomedicines, vol. 9, no. 9, 1186. https://doi.org/10.3390/biomedicines9091186

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

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.",

keywords = "Adeno‐associated virus (AAV) vector, Large animal model, Monoclonal antibody, Safety, Tolerability, Vectored immunoprophylaxis",

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year = "2021",

month = sep,

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AU - Rghei, Amira D.

AU - van Lieshout, Laura P.

AU - McLeod, Benjamin M.

AU - Pei, Yanlong

AU - Lopes, Jordyn A.

AU - Zielinska, Nicole

AU - Baracuhy, Enzo M.

AU - Stevens, Brenna A.Y.

AU - Thomas, Sylvia P.

AU - Yates, Jacob G.E.

AU - Warner, Bryce M.

AU - Kobasa, Darwyn

AU - Fausther‐bovendo, Hugues

AU - Kobinger, Gary P.

AU - Karimi, Khalil

AU - Thompson, Brad

AU - Bridle, Byram W.

AU - Susta, Leonardo

AU - Wootton, Sarah K.

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

PY - 2021/9

Y1 - 2021/9

N2 - 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.

AB - 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.

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KW - Tolerability

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

Abstract

Keywords

ASJC Scopus subject areas

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