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

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 and Andrea Marzi ()
Additional contact information
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
Jesse H. Erasmus: HDT Bio
Andrea Marzi: National Institutes of Health

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59560-1

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