Diary Prequel Package — page 361

understand. At this time, we are unclear about the positive versus negative effects of cytokine secretion (or call it dysregulation) related to the precise cytokines in question and the timing of their secretion vis-à-vis Ebola infection (see first bullet in the first of 2 slides in the first attachment. In my mind, this does not mean that one should not provide VSV as PEP for your people (or others); however, if administered to them, it should be made clear to the recipients that 1) VSV Ebola vaccine provided 50% protection in monkeys if given 20-30 minutes following exposure. I would mention that monkey models are somewhat different from human Ebola (see 3rd and 4th bullet of 2nd slide in first attachment) and so direct extrapolation to humans should be made with caution at this point in time; and 2) importantly, the vaccine recipients should clearly understand that there is a theoretical possibility that the VSV, due to the complexities of the cytokine dysregulation that accompanies Ebola infection and the perturbation of this cytokine network that might occur with a live virus vaccine (VSV) that induces inflammation and fever, might actually cause them harm by disturbing their normal inflammatory/immune response to Ebola infection. If they understand these caveats, then it would be their choice to receive the vaccine with informed consent. Finally, as you certainly know better than anyone, the FDA will have to be involved in the approval of allowing this pre-positioning and potential use of an experimental vaccine by whatever is the appropriate regulatory mechanism. I hope that this information is helpful to you in your deliberations about PEP. I look forward to discussing these issues with you. Best regards, Tony -----Original Message----- From: Frieden, Thomas (Tom) (CDC/OD) Sent: Sunday, August 31, 2014 3:49 AM To: Fauci, Anthony (NIH/NIAID) [E] Subject: Cytokine I had heard of cytokine storm with tekmira but not with VSV. Can you confirm? Did MSNBC Sept. 1, 2014 - Labor Day - had usual call with Secretary Burwell (SMB) this AM at 8:30 AM. Clear and muggy day. We are going around in circles. I am concerned that the Secretary is a really smart and very competent person, but she is surrounded by people who may be good at management, but who have never been in a situation like this and who really do not have a clue how to address it → Leslie Dach (formerly of Walmart); Andrea Palm (have no idea where she came from). Bill Corr (Deputy Secretary) is the only one with corporate memory of former crises and he has been completely marginalized by the new kids in town.