Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection

Pooja Munnilal Tiwari, Daryll Vanover, Kevin E. Lindsay, Swapnil Subhash Bawage, Jonathan L. Kirschman, Sushma Bhosle, Aaron W. Lifland, Chiara Zurla and Philip J. Santangelo ()
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Pooja Munnilal Tiwari: Georgia Institute of Technology and Emory University
Daryll Vanover: Georgia Institute of Technology and Emory University
Kevin E. Lindsay: Georgia Institute of Technology and Emory University
Swapnil Subhash Bawage: Georgia Institute of Technology and Emory University
Jonathan L. Kirschman: Georgia Institute of Technology and Emory University
Sushma Bhosle: Georgia Institute of Technology and Emory University
Aaron W. Lifland: Georgia Institute of Technology
Chiara Zurla: Georgia Institute of Technology and Emory University
Philip J. Santangelo: Georgia Institute of Technology and Emory University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract The lung is a critical prophylaxis target for clinically important infectious agents, including human respiratory syncytial virus (RSV) and influenza. Here, we develop a modular, synthetic mRNA-based approach to express neutralizing antibodies directly in the lung via aerosol, to prevent RSV infections. First, we express palivizumab, which reduces RSV F copies by 90.8%. Second, we express engineered, membrane-anchored palivizumab, which prevents detectable infection in transfected cells, reducing in vitro titer and in vivo RSV F copies by 99.7% and 89.6%, respectively. Finally, we express an anchored or secreted high-affinity, anti-RSV F, camelid antibody (RSV aVHH and sVHH). We demonstrate that RSV aVHH, but not RSV sVHH, significantly inhibits RSV 7 days post transfection, and we show that RSV aVHH is present in the lung for at least 28 days. Overall, our data suggests that expressing membrane-anchored broadly neutralizing antibodies in the lungs could potentially be a promising pulmonary prophylaxis approach.

Date: 2018
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DOI: 10.1038/s41467-018-06508-3

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