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Single-dose replicon RNA Sudan virus vaccine uniformly protects female guinea pigs from disease

Author

Listed:
  • Kyle L. O’Donnell

    (National Institutes of Health)

  • Hanna Anhalt

    (National Institutes of Health)

  • Greg Saturday

    (National Institutes of Health)

  • Nikole L. Warner

    (HDT Bio)

  • Troy Hinkley

    (HDT Bio)

  • E. Taylor Stone

    (HDT Bio)

  • Kiara Hatzakis

    (HDT Bio)

  • Amit P. Khandhar

    (HDT Bio)

  • Logan Banadyga

    (Public Health Agency of Canada
    University of Manitoba)

  • Jesse H. Erasmus

    (HDT Bio)

  • Andrea Marzi

    (National Institutes of Health)

Abstract

The Sudan virus (SUDV) outbreaks in Uganda in 2022 and 2025 created public health concerns in-country and the entire East African region. There are currently no licensed countermeasures against SUDV. We developed a SUDV vaccine candidate based on a nanocarrier (LIONTM) complexed with an alphavirus-based replicon RNA. Here, we compare the protective efficacy of the LION-SUDV vaccine either encoding the SUDV glycoprotein (GP) alone or in combination with the Ebola virus (EBOV) GP (LION-Combination). A LION-EBOV vaccine which is protective against EBOV was also included to determine the potential for cross-protection against SUDV infection. Single-dose vaccinations were conducted three weeks before challenge with a lethal dose of guinea pig-adapted SUDV using a female guinea pig disease model. We demonstrate 100% survival and protection with the LION-SUDV and the LION-Combination vaccines, while the LION-EBOV vaccine achieved 50% protection. Antigen-specific humoral responses correlate with decreased virus replication and survival. This result warrants further studies in larger animal species to ensure that protective efficacy is maintained with the single-dose LION-SUDV vaccine.

Suggested Citation

  • Kyle L. O’Donnell & Hanna Anhalt & Greg Saturday & Nikole L. Warner & Troy Hinkley & E. Taylor Stone & Kiara Hatzakis & Amit P. Khandhar & Logan Banadyga & Jesse H. Erasmus & Andrea Marzi, 2025. "Single-dose replicon RNA Sudan virus vaccine uniformly protects female guinea pigs from disease," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59560-1
    DOI: 10.1038/s41467-025-59560-1
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