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Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection

Author

Listed:
  • 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)

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.

Suggested Citation

  • Pooja Munnilal Tiwari & Daryll Vanover & Kevin E. Lindsay & Swapnil Subhash Bawage & Jonathan L. Kirschman & Sushma Bhosle & Aaron W. Lifland & Chiara Zurla & Philip J. Santangelo, 2018. "Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06508-3
    DOI: 10.1038/s41467-018-06508-3
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    Cited by:

    1. Erwin De Genst & Kylie S. Foo & Yao Xiao & Eduarde Rohner & Emma de Vries & Jesper Sohlmér & Nevin Witman & Alejandro Hidalgo & Terje R. S. Kolstad & William E. Louch & Susanne Pehrsson & Andrew Park , 2022. "Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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