Diary Prequel Package — page 360

ure. contamination of hands outside of the classical hospital setting should in my mind at least be considered as a potential route of transmission. Press interest continues with: Columbia (Bogota) Radio; VOA TV; NPR Weekend Edition with Scott Simon; NPR Science Friday; CNN with Jake Tapper; Reuters TV August 30, 2014 - Case from Guinea went to Dakar, Senegal and lied about exposure. Took bus and stopped in 2 health care facilities. Contact tracing now going on in Senegal. Spoke with Tom Frieden who is in Liberia. Trying to get him to appreciate that giving VSV Ebola vaccine as post-exposure prophylaxis (PEP) is risky due to the induction of cytokines by the live VSV, which might actually enhance the acquisition upon exposure since cytokine dysregulation plays a negative and potentially positive role in Ebola virus disease. He wants to pre-position VSV vaccine for PEP and TKM drug (siRNA - not yet is phase 1) at all Ebola treatment Units (ETUs). I understand the desire to protect the CDC and other health care workers on the front lines, but we must be concerned about giving drugs/PEP vaccines BEFORE they have even been in the earliest Phase 1 trials. Yesterday CDC evacuated a WHO worked who had a low risk needle stick (clean needle through potentially contaminated gloves) and they gave the person TKM drug and wanted to give VSV, but could not get it. That is why he now wants to pre-position it. See below my e-mail to Tom Frieden sent to him on Sunday, August 31 while he was in Liberia: Tom: I am including a few attachments: 1) 2 slides (from Nancy Sullivan who does our pre-clinical Ebola studies) that summarize the issue of "cytokine dysregulation" in Ebola disease and potentially following vaccination; 2) 2 reprints (referred to in the 2 slides) on the types of cytokine responses in Ebola disease and following vaccination with different vaccine platforms; and 3) the Heinz Feldmann paper with which you are familiar and which shows that in the monkey model of Ebola virus disease, the VSV Ebola vaccine used as post exposure prophylaxis (PEP) protected 50% of the monkeys from lethal challenge with Ebola if administered 20-30 minutes following the challenge. Getting back to our discussion and your question concerning the issue of any risk of administering VSV as PEP, I certainly would not characterize the inflammation following VSV vaccine administration as "cytokine storm". It certainly induces inflammation and can cause fever. Note that the only human to my knowledge who received this vaccine was the laboratory worker in Germany who had a needle stick injury and she got a fever following vaccination. Inflammation that results in fever will virtually always induce secretion of cytokines of various sorts. Since VSV in the NewLink vaccine is a replicating virus, it will almost certainly induce the secretion of cytokines. The reason that this might be important is that a whole array of cytokines are important in the pathogenesis of Ebola virus disease. It certainly can kill you (advanced cytokine storm) and it is almost certainly involved in protection and recovery from Ebola infection. It is a delicate balance that we do not fully