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Updated: Jun 17, 2026
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Efficacy of ST-246 versus lethal poxvirus challenge in immunodeficient mice
Douglas W Grosenbach1, Aklile Berhanu, David S King
1SIGA Technologies Inc, Corvallis, OR 97333, USA.
Abstract:
The threat of smallpox as a bioweapon and the emerging threat of human monkeypox, among other poxviral diseases, highlight the need for effective poxvirus countermeasures. ST-246, which targets the F13L protein in vaccinia virus and its homologs in other orthopoxvirus species, provides full protection from lethal poxviral disease in numerous animal models and seems to be safe in humans. All previous evaluations of ST-246 efficacy have been in immunocompetent animals. However, the risk of severe poxviral disease is greater in immunodeficient hosts. Here we report on the efficacy of ST-246 in preventing or treating lethal poxviral disease in immunodeficient mice. After lethal challenge with the Western Reserve strain of vaccinia, Nude, SCID, and J(H) knockout mice additionally depleted of CD4(+) and CD8(+) T cells were not fully protected by ST-246, although survival was significantly extended. However, CD4(+) T cell deficient, CD8(+) T cell deficient, J(H) knockout, and J(H) knockout mice also deficient for CD4(+) or CD8(+) T cells survived lethal challenge when treated with ST-246 starting on the day of challenge. Delaying treatment until 72 h after infection reduced ST-246 efficacy in some models but provided full protection from lethal challenge in most. These findings suggest that ST-246 may be effective in controlling smallpox or other pathogenic orthopoxviruses in some immunodeficient human populations for whom the vaccine is contraindicated.
Insights
ST-246 offers protection against poxviral diseases in immunodeficient mice, extending survival and providing full protection when treatment begins early. This suggests potential for controlling smallpox in vulnerable populations.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Poxviral diseases, including smallpox and monkeypox, pose significant bioweapon threats.
- Effective countermeasures are crucial, especially for vulnerable populations.
- ST-246 is a promising antiviral targeting the F13L protein, showing efficacy in immunocompetent models.
Purpose of the Study:
- To evaluate the efficacy of ST-246 in preventing and treating lethal poxviral disease in immunodeficient mouse models.
- To determine if ST-246 is effective in hosts with compromised immune systems, where poxviral disease risk is higher.
Main Methods:
- Lethal challenge with vaccinia virus (Western Reserve strain) in various immunodeficient mouse models (Nude, SCID, J(H) knockout, T cell-depleted).
- Administration of ST-246 at different time points (day of challenge, 72 hours post-infection).
- Assessment of survival rates and disease severity as efficacy indicators.
Main Results:
- ST-246 did not provide full protection in severely immunodeficient mice (e.g., T cell-depleted), but significantly extended survival.
- Mice with partial immunodeficiency (e.g., CD4(+) or CD8(+) T cell deficient) showed full survival when treated with ST-246 starting on the day of challenge.
- Delayed ST-246 treatment (72 hours post-infection) reduced efficacy in some models but still provided significant protection in most.
Conclusions:
- ST-246 demonstrates efficacy in controlling poxviral infections in various immunodeficient settings.
- Early ST-246 treatment is critical for optimal outcomes in immunodeficient hosts.
- Findings suggest ST-246's potential utility for managing smallpox and other orthopoxvirus infections in human populations where vaccination is contraindicated.
