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A self-amplifying RNA RSV prefusion-F vaccine elicits potent immunity in pre-exposed and naïve non-human primates

Author

Listed:
  • Aneesh Vijayan

    (Janssen Vaccines and Prevention B.V.
    Artemis Bioservices)

  • Ronald Vogels

    (Janssen Vaccines and Prevention B.V.)

  • Rachel Groppo

    (Johnson & Johnson Innovative Medicine)

  • Yi Jin

    (Johnson & Johnson Innovative Medicine)

  • Selina Khan

    (Janssen Vaccines and Prevention B.V.
    Oncode Accelerator Foundation)

  • Mirjam Kampen

    (Janssen Vaccines and Prevention B.V.)

  • Sytze Jorritsma

    (Janssen Vaccines and Prevention B.V.)

  • Satish Boedhoe

    (Janssen Vaccines and Prevention B.V.)

  • Miranda Baert

    (Janssen Vaccines and Prevention B.V.
    Leiden Medical University)

  • Harry Diepen

    (Janssen Vaccines and Prevention B.V.)

  • Harmjan Kuipers

    (Janssen Vaccines and Prevention B.V.)

  • Jan Serroyen

    (Janssen Vaccines and Prevention B.V.)

  • Jorge Reyes- Valle

    (Johnson & Johnson Innovative Medicine)

  • Ann Broman

    (Johnson & Johnson Innovative Medicine)

  • Lannie Nguyen

    (Johnson & Johnson Innovative Medicine)

  • Sayoni Ray

    (Johnson & Johnson Innovative Medicine)

  • Bader Jarai

    (Johnson & Johnson Innovative Medicine)

  • Jayant Arora

    (Johnson & Johnson Innovative Medicine)

  • Michelle Lifton

    (Harvard Medical School.)

  • Benjamin Mildenberg

    (Harvard Medical School.)

  • Georgeanna Morton

    (Harvard Medical School.)

  • Sampa Santra

    (Harvard Medical School.)

  • Tamar R. Grossman

    (Johnson & Johnson Innovative Medicine)

  • Hanneke Schuitemaker

    (Janssen Vaccines and Prevention B.V.)

  • Jerome Custers

    (Janssen Vaccines and Prevention B.V.)

  • Roland Zahn

    (Janssen Vaccines and Prevention B.V.)

Abstract

Newly approved subunit and mRNA vaccines for respiratory syncytial virus (RSV) demonstrate effectiveness in preventing severe disease, with protection exceeding 80% primarily through the generation of antibodies. An alternative vaccine platform called self-amplifying RNA (saRNA) holds promise in eliciting humoral and cellular immune responses. We evaluate the immunogenicity of a lipid nanoparticle (LNP)-formulated saRNA vaccine called SMARRT.RSV.preF, encoding a stabilized form of the RSV fusion protein, in female mice and in non-human primates (NHPs) that are either RSV-naïve or previously infected. Intramuscular vaccination with SMARRT.RSV.preF vaccine induces RSV neutralizing antibodies and cellular responses in naïve mice and NHPs. Importantly, a single dose of the vaccine in RSV pre-exposed NHPs elicits a dose-dependent anamnestic humoral immune response comparable to a subunit RSV preF vaccine. Notably, SMARRT.RSV.preF immunization significantly increases polyfunctional RSV.F specific memory CD4+ and CD8+ T-cells compared to RSV.preF protein vaccine. Twenty-four hours post immunization with SMARRT.RSV.preF, there is a dose-dependent increase in the systemic levels of inflammatory and chemotactic cytokines associated with the type I interferon response in NHPs, which is not observed with the protein vaccine. We identify a cluster of analytes including IL-15, TNFα, CCL4, and CXCL10, whose levels are significantly correlated with each other after SMARRT.RSV.preF immunization. These findings suggest saRNA vaccines have the potential to be developed as a prophylactic RSV vaccine based on innate, cellular, and humoral immune profiles they elicit.

Suggested Citation

  • Aneesh Vijayan & Ronald Vogels & Rachel Groppo & Yi Jin & Selina Khan & Mirjam Kampen & Sytze Jorritsma & Satish Boedhoe & Miranda Baert & Harry Diepen & Harmjan Kuipers & Jan Serroyen & Jorge Reyes- , 2024. "A self-amplifying RNA RSV prefusion-F vaccine elicits potent immunity in pre-exposed and naïve non-human primates," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54289-9
    DOI: 10.1038/s41467-024-54289-9
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    References listed on IDEAS

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    1. Kaori Sano & Disha Bhavsar & Gagandeep Singh & Daniel Floda & Komal Srivastava & Charles Gleason & Juan Manuel Carreño & Viviana Simon & Florian Krammer, 2022. "SARS-CoV-2 vaccination induces mucosal antibody responses in previously infected individuals," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    2. 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.
    3. Amy R. Rappaport & Sue-Jean Hong & Ciaran D. Scallan & Leonid Gitlin & Arvin Akoopie & Gregory R. Boucher & Milana Egorova & J. Aaron Espinosa & Mario Fidanza & Melissa A. Kachura & Annie Shen & Glori, 2022. "Low-dose self-amplifying mRNA COVID-19 vaccine drives strong protective immunity in non-human primates against SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
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