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Universal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein

Author

Listed:
  • Johannes P. M. Langedijk

    (Janssen Vaccines & Prevention BV
    ForgeBio)

  • Freek Cox

    (Janssen Vaccines & Prevention BV)

  • Nicole V. Johnson

    (The University of Texas at Austin)

  • Daan Overveld

    (Janssen Vaccines & Prevention BV)

  • Lam Le

    (Janssen Vaccines & Prevention BV)

  • Ward Hoogen

    (Janssen Vaccines & Prevention BV)

  • Richard Voorzaat

    (Janssen Vaccines & Prevention BV)

  • Roland Zahn

    (Janssen Vaccines & Prevention BV)

  • Leslie Fits

    (Janssen Vaccines & Prevention BV)

  • Jarek Juraszek

    (Janssen Vaccines & Prevention BV)

  • Jason S. McLellan

    (The University of Texas at Austin)

  • Mark J. G. Bakkers

    (Janssen Vaccines & Prevention BV
    ForgeBio)

Abstract

The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness.

Suggested Citation

  • Johannes P. M. Langedijk & Freek Cox & Nicole V. Johnson & Daan Overveld & Lam Le & Ward Hoogen & Richard Voorzaat & Roland Zahn & Leslie Fits & Jarek Juraszek & Jason S. McLellan & Mark J. G. Bakkers, 2024. "Universal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48059-w
    DOI: 10.1038/s41467-024-48059-w
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    References listed on IDEAS

    as
    1. Jarek Juraszek & Lucy Rutten & Sven Blokland & Pascale Bouchier & Richard Voorzaat & Tina Ritschel & Mark J. G. Bakkers & Ludovic L. R. Renault & Johannes P. M. Langedijk, 2021. "Stabilizing the closed SARS-CoV-2 spike trimer," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    2. Ariel Isaacs & Yu Shang Low & Kyle L. Macauslane & Joy Seitanidou & Cassandra L. Pegg & Stacey T. M. Cheung & Benjamin Liang & Connor A. P. Scott & Michael J. Landsberg & Benjamin L. Schulz & Keith J., 2023. "Structure and antigenicity of divergent Henipavirus fusion glycoproteins," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Jan Felix Drexler & Victor Max Corman & Marcel Alexander Müller & Gael Darren Maganga & Peter Vallo & Tabea Binger & Florian Gloza-Rausch & Veronika M. Cottontail & Andrea Rasche & Stoian Yordanov & A, 2012. "Bats host major mammalian paramyxoviruses," Nature Communications, Nature, vol. 3(1), pages 1-13, January.
    4. Michael B. Battles & Vicente Más & Eduardo Olmedillas & Olga Cano & Mónica Vázquez & Laura Rodríguez & José A. Melero & Jason S. McLellan, 2017. "Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    5. Hsien-Sheng Yin & Xiaolin Wen & Reay G. Paterson & Robert A. Lamb & Theodore S. Jardetzky, 2006. "Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation," Nature, Nature, vol. 439(7072), pages 38-44, January.
    6. Anders Krarup & Daphné Truan & Polina Furmanova-Hollenstein & Lies Bogaert & Pascale Bouchier & Ilona J. M. Bisschop & Myra N. Widjojoatmodjo & Roland Zahn & Hanneke Schuitemaker & Jason S. McLellan &, 2015. "A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
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