Scientific Publications by FDA Staff

J Virol 2009 Oct;83(20):10437-47

Application of bioluminescence imaging to the prediction of lethality in vaccinia virus infected mice.

Zaitseva M, Kapnick SM, Scott J, King LR, Manischewitz J, Sirota L, Kodihalli S, Golding H

To find an alternative endpoint for efficacy of anti-smallpox treatments, bioluminescence was measured in live Balb/c mice following lethal challenge with a recombinant WR vaccinia virus expressing luciferase. VIGIV treatments were used to confer protection in a proportion of animals. Using known lethality outcomes in 200 animals and total fluxes recorded daily in live animals, we performed univariate Receiver-Operating Characteristic (ROC) curve analysis to assess whether lethality can be predicted based on bioluminescence. Total fluxes in the spleens on day 3 and in the livers on day 5 generated accurate predictive models; AUC=0.91. Multiple logistic regression analysis utilizing a linear combination of six measurements: total flux in the liver on days 2, 3, and 5; spleen on days 1 and 3, and nasal cavity on day 4 generated most accurate predictions; AUC=0.96. This model predicted lethality in 90% of animals with only 10% of non-surviving animals incorrectly predicted to survive. Compared with bioluminescence, ROC analysis of 25% and 30% weight loss as thresholds accurately predicted survival on day 5 but lethality predictions were low until day 9. Collectively, our data support the use of bioimaging for lethality prediction following vaccinia challenge and for gaining an insight on protective mechanisms conferred by vaccines and therapeutics.