Vaccine Update - plasmapheresis time!

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Long time no update! A few days ago, I was informed by the study team that I had  either the highest or second highest (they wouldn't specify) immune response to the experimental Ebola vaccine. As such, they are interested in harvesting the antibodies that my body has generated for use in a potential transfusion to a patient suffering from an Ebola attack. I'm glad my white blood cells are such active little guys! Side note: the data this decision was made on was based on an analysis of my blood conducted in December. The analysis takes a while, so rather than wait to see what my blood has looked like over the past few months the team decided to go ahead and retrieve my plasma now. Using premade antibodies provides an Ebola patient with an extra leg up on the disease. Antibodies are used by the body to discern which things in the body aren't supposed to be there (antigens), so having antibodies against Ebola allows an Ebola patient's immune system to recognize the virus faster and mount a defense of its own. This is how ZMapp worked, which was a monoclonal antibody produced in a tobacco plant that was given to a few of the earliest health workers returning from Africa with Ebola.

To get this process started, I underwent what is known as a plasmapheresis. This is when the staff at the clinical center harvests my plasma, which is the "liquid" part of the blood and is the part that contains all of the antibodies that I have against Ebola. About 55% of your blood is made up plasma. This plasma is then split into different parts and frozen, ready for use should the need arise. A small portion will also be used for further research.

You may have friends who have had this procedure done before - it's not that uncommon! In essence, my blood is removed , spun in a centrifuge, the plasma is removed and the remaining components of the blood are returned to me. The apparatus looks something like this:

Figure 1: The plasmapheresis process. Note that my red blood cells, white blood cells, and platelets are returned to me with the addition of some saline to make up for fluid loss.

And my procedure looked something like this:

Figure 2: The fairly large needle in my arm is able to both draw and return blood, no second needle necessary!

Figure 2: The fairly large needle in my arm is able to both draw and return blood, no second needle necessary!

Figure 3: The resulting plasma and the fantastic nurses at the NIH Clinical Center!

Figure 3: The resulting plasma and the fantastic nurses at the NIH Clinical Center!

All in all, it was a very pleasant experience! The only side effects that people tend to experience is a feeling of faintness, similar to what you would feel during a typical blood donation. The machine also circulates an anticoagulant through the blood, which ensures that the blood doesn't gunk up the system. The anticoagulant can cause tingling in the lips and fingers, but I didn't have any of that. The bed I was in had a memory foam mattress and I was given copious snacks upon the completion of the collection. I'll start with giving three times - the protocol itself allows for up to 20 collections. Hopefully my nurses aren't tired of me by then!

A little vaccine update

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Last week, I received a booster dose of the VSV-EBOV Ebola vaccine that I've blogged about before, and I'm happy to report that I had no symptoms this go around. This is a pretty stark contrast from when I got my first dose...a 101.6 degreefever and terrible joint pain make for a pretty miserable evening!

Figure 1: A picture of the vaccine, isn't it cute?

Figure 1: A picture of the vaccine, isn't it cute?

Since starting the trial, a few bits of news regarding this particular vaccine have come out. An article from NPR a few weeks ago noted that a vaccine trial in Switzerland using the same vaccine noted increased joint pain in their patients, leading them to stop the trial. I also had pretty significant joint pain, but our trial here at the NIH is trucking along pretty nicely. Huzzah!

NewLink Genetics, the company that produces the vaccine, was also awarded a $30 million grant today from the US Department of Health and Human Services (HHS) to manufacture and develop the vaccine in collaboration with pharmaceutical giant Merck. The NIH also announced that they will initiate further phases of the clinical trial next year. Keep your eyes and ears out for updates on how this story evolves!

Rough.

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If you recall, I mentioned that there was a possibility that I would receive the placebo in my clinical trial, which is just saline. Well, it looks like I actually received the vaccine... As the day went on yesterday, my joints started to feel really achy. Hips, knees, and lower back. At one point during the night, it felt like someone had tied my legs to a truck and told it to drive off - ouch! My temperature also hit about 101.6 degrees, which is a pretty good fever. What's worse is that my raging fever alternated with strong chills, so I had to adapt to feelings ranging from hellfire to Arendelle.  I know this is for the good of humanity and whatnot, but there were definitely points last night where I thought to myself, "Damn, was this worth it?".

And it definitely was! As sudden as the symptoms began, they left without a trace. I woke up this morning feeling great and my fever had completely abated. I went for my regularly scheduled appointment and blood draw and my nurse said I was good to go! If my case is at all similar to the other patients in my cohort, I should be in the clear for the time being. I'll be receiving a booster shot of the vaccine in about a month, so I'll let you know if it's any better the second time around! At least I'm theoretically immune to Ebola, right?

Have a stellar weekend!

Ebola vaccines and pipelines: Where are we now?

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With the Ebola virus raging on in West Africa, scientists and clinicians around the world are racing to develop feasible treatments and vaccines. Here in the United States, there are currently two vaccines in Phase I clinical trials here at the National Institutes of Health. But what does that mean in terms of development? Are we close to deploying these therapies in Africa? To illustrate the typical path of development for drugs, here's a little graphic produced by Nature Drug Discovery:

Figure 1: The drug development pipeline. Note that the Ebola vaccines are currently in Phase I studies!

Figure 1: The drug development pipeline. Note that the Ebola vaccines are currently in Phase I studies!

As a side note, the NIH center where I work focuses on the stage just before Phase I, which is preclinical development. As the title implies, Phase I-III trials are conducted in human patients in the clinic. Briefly, here is a summary of the three different phases:

Phase I: Safety. In this phase, the vaccine is given to healthy individuals to determine if the vaccine is safe in humans and to establish what doses are safe. The virus in question is NOT given to the patient in this phase - this is simply to test if the vaccine by itself is safe.

Phase II: Efficacy. In this phase, the vaccine is given at full therapeutic dose to patients with the virus to determine whether or not it is effective. There are plans in motion to send doses of the vaccines to West Africa for this purpose.

Phase III: More efficacy! In this phase, the trial is expanded to a much larger amount of participants in a final determination of biological effectiveness.

These trials normally take years to complete, but due to the desperate need for therapeutics the "typical" pipeline is being greatly enhanced. The Phase 1 trials are underway, so hopefully GlaxoSmithKline and NewLink Genetics (the two companies with intellectual property rights in the vaccines) will be able to finish the entire pipeline as soon as possible. I'll go into more details as to how the current vaccines work in a few days, but keep an eye on the news to see if any new experimental drugs pop up!

Hijacked!

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First, a big "thank you" to all of you who have joined in reading my blog! I appreciate all of your support and I sincerely hope you enjoy exploring science with me! With the recent outbreaks of Ebola in West Africa and the isolated cases in the United States and the rest of the western world dominating headlines, your fears over the emergence of this and other viruses have probably increased quite dramatically in the past few weeks! But how can a virus, considered nonliving in the world of biology, become so dangerous? As you may have guessed based on the title of this post, it all lies in the ability of the virus to hijack your cells. Deception, cunning, betrayal. A viral infection has all of the makings of a great spy movie!

As I was sipping my coffee this morning and scanning the headlines, I spotted a very interesting paper published in Science that described how Influenza A virus (IAV, which kills between 250,000 and a few million people very year) uses your own cells against you. To illustrate how this all works, here's a schematic created by the team at Science about how the virus gets into your cells:

Figure 1: Influenza A getting to work! Sneaky sneaky!

Figure 1: Influenza A getting to work! Sneaky sneaky!

Let's start at the very beginning! The virus, shown in yellow, is engulfed by your cells via a process known as endocytosis. Once the virus is enveloped in an endosome (the bubble like structure that results from an object being ingested), the virus begins to increase the acidity within that environment. This increase in acidity results in a fusion of the virus with the endosome, which marks the beginning of Influenza's grand escape.

The goal that the virus is pursuing is to inject its payload into your cell's nucleus. This payload includes things such as viral enzymes and RNA, which the host cell (you) will use to produce viral DNA and viral proteins. This is very clever, as your cell will just assume that genetic material in the nucleus needs to be converted into proteins. At this point, the virus has won! But as you can see from the image above, the virus is enveloped in its own shell that must be broken in order to deliver these things into the nucleus.

To make that happen, Influenza A waves around a little protein called ubiquitin, which is actually a signal your cells used to determine what things need to be degraded. Once your cell sees this signal, it sends proteins to go after the virus in an attempt to degrade it, which was the focus of the paper mentioned at the beginning of this post.

Now here's when things start to get a little mysterious! In the same vein as your favorite murder mystery, there is a span of time in this process that we just can't seem to account for. Experimentally, the authors have shown that something happens in between the recruitment of degradation proteins and the breaking of the viral shell, but we aren't sure exactly what that is. But whatever mechanism that the virus is taking advantage of to break itself free, it will likely become a very promising drug target.

No breakage = no payload delivery = no infection. Virologists, start your engines! The search is on!

*Author's note* Ebola is also an encapsulated virus; thus, it must also break free of its shell to deliver its payload. To what extent it uses the above mechanism performed by its brethren remains to be seen!