Experimental Ebola vaccine appears safe, prompts immune response | Hacker News Reader

Experimental Ebola vaccine appears safe, prompts immune response

nih.gov

78 pointsadamnemecek30 comments

I am excited, but I would rather wait until a Phase 3 result before getting my hopes up. Phase 1 is just to verify that the vaccine doesn't kill you all by itself.

http://en.wikipedia.org/wiki/Clinical_trial#Phases

It might also be good to remember some of the history around why this structure is in place.

The Battle to Beat Polio: http://youtu.be/qMRgQhbSyqs?t=18m50s

In the case of vaccines, phase one trials tell you if there's an immune response to the antigen being used. This is a good first approximation of effectiveness.

The level of response could still be too low, but at least there's something happening.

Clinical trial phases with vaccines are less useful than they are with drugs. The major problems with vaccines are either they don't work (or don't work very well) or they cause (or are thought to cause) rare but serious side effects. Neither of these are normally able to picked up in phase 1 or 2 trials.

It's been a while since I've seen anything on HN about the Ebola outbreak.. so here's the current news if anyone's interested:

Number of Ebola infections in west Africa passes 16,000 http://www.theguardian.com/world/2014/nov/29/ebola-infection...

CDC chart: http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/cumu...

Cool. I hope they now try giving the virus to health workers in west Africa rather than mucking about with US trials while thousands die out there.

For those down voting, there are about 1500 new cases a week currently of which say 1000 will die. If you delay using the vaccine for a couple of years while doing normal phase 2 and 3 trials then even with linear growth that would be approx 100,000 nasty deaths. In comparison about the worst that has happened using vaccines too early was about 20 people killed in by the early polio vaccines and accidental deaths now would probably be about zero given better science. Would it be worth having 100,000 extra deaths so conventional procedures can be respected? Why not proceed in a way calculated to minimise overall deaths and suffering?

One thing you're forgetting is that it'll take a Maximum Effort to actually get mass quantities of people vaccinated. Especially if the vaccine requires refrigeration.

This, in an environment where fear, a common feature to all deadly epidemics, is a primary driving force.

Any significant fraction of vaccine administrations resulting in morbidity or mortality, or having to do it all over again with an actually effective vaccine ... well, it won't end well. I'm not sure you'd get a second try with another one.

Yes. But notice that the original poster said to give this thing to health care workers first. I think that's a fairly reasonable position to take given that the confidence in the safety of the vaccine is high, and that even if the health care workers were given the vaccine, they should be following the same decontamination/personal protection protocols anyways (for person health reasons - no vaccine is 100% perfect and for public health reasons - it minimizes cross infection).

In addition, it is possible to do accelerated Phase 2/3 in Africa. This is also a compromise position. In this scheme, they would likely dispense a few thousand vaccines in a relatively highly developed, but still high risk area to aid in their ability to track efficacy. From the NIH FAQ on Ebola vaccines (http://www.niaid.nih.gov/news/QA/Pages/EbolaVaxResultsQA.asp...)

  Given the encouraging results of the bivalent version of the NIAID/GSK experimental Ebola vaccine at the NIH Clinical Center, are there plans for Phase 2/3 clinical trials in West Africa?

  NIAID is in active discussions with Liberian officials and other partners about next-stage vaccine testing in West Africa. The goal of these studies would be to test efficacy and safety of the NIAID/GSK vaccine compared to other Ebola vaccine candidates prior to wider vaccine distribution. Phase 2/3 clinical trials are designed to inform efficacy—whether or not the vaccine works—and provide additional critical safety data. Plans for such studies are dependent on additional safety and immunogenicity data derived from the currently ongoing clinical trials. Announcements about larger-scale testing will not be made until early 2015.

Keep in mind that is basically is impossible to do Phase 2 and 3 testing in North America given the fact that there basically isn't any Ebola there at all.

Indeed. And after testing it on volunteers in the U.K. and maybe US (it is being tested in Bethesda by the NIH, I don't know the timing), this particular vaccine is being tested on volunteer healthcare workers in Mali, see e.g. http://www.citypress.co.za/news/africas-first-ebola-vaccine-... (I think they've tested it on more people since that article, you no doubt want to go a bit slowly since many of the worst reactions are fairly quick). And I think there are some other African locations scheduled.

Vaccines and epidemics are a pretty well understood concepts after all (ignore the "public health" types who are obsessed with lifestyle etc. issues to the detriment of infectious diseases, like the current head of the CDC), there's no surprise people are attempting to Do The Right Thing with these candidate vaccines. E.g. as I note elsewhere in this discussion, this one is in the process of being produced at an intermediate scale of 10,000 doses, which is a necessary step before true mass production.

Update - they do seem to be trying to crack on:

"Ebola Vaccine May Be Ready as Early as January 2015"

"If further clinical trials result in an effective vaccine, health care workers who treat those with Ebola will likely be the first to receive it."

http://newsone.com/3074615/ebola-vaccine-may-be-ready-as-ear...

What it's cost?

That’s not nearly as interesting a question as “Is it patented?”.

Well it's really nearly the same question isn't it?

No, not really. If it is patented, the owner of the patent might charge a lot for it, or they might give out licenses cheaply out of the goodness of their hearts. If it is not patented, it might be cheap if there are many manufacturers, or it might be expensive if there are few manufacturers (for whatever reason). It might also be intrinsically expensive to manufacture, in which case the result will also necessarily be expensive.

So really, the questions are nearly completely unrelated.

The cost to manufacture is still quite interesting.

Although in this era of modern biotechnology, especially for a 3rd World targeted vaccine, it would be appalling to develop one that was expensive to manufacture. I.e. nothing like the standard old flu vaccine, which is grown in the membranes of chicken eggs, yielding about 3 doses from each egg. Compare to e.g. the Protein Sciences method, which uses genetically modified insect cells in a bioreactor, which as I recall produces about 100,000 doses in a week or so (although it normally takes another 5-7 weeks to finish the vaccine once a batch of raw antigen is done).

Url changed from http://www.iflscience.com/health-and-medicine/ebola-vaccine-..., which quotes from it without referencing it.

Convenient timing!

Well why are we not starting to mass produce it then? Yeah yeah normally we would wait years and do a lot of tests but people are dying _now_ and we have already given experimental medication, so that ethical level has been crushed.

So should we pay millions of dollars to any company that claims they have a vaccine to Ebola, just because they say they do? It's not free - so we can't just mass produce whatever miracle drug someone claims to have and keep our fingers crossed that it works.

See my other comment. The stakes are high enough it's worth spending a few million on the intermediate step towards mass production. By the time that's done, hopefully we'll know if the vaccine is any good.

We can't? http://www.macleans.ca/society/health/canadas-questionable-t... http://www.webmd.boots.com/cold-and-flu/news/20140103/govern...

So your argument is that two wrongs make a right?

They already are taking the first step in mass production, making 10,000 doses funded by a foundation and the U.K. government (http://www.theguardian.com/society/2014/sep/17/ruth-atkins-f...).

When you do this sort of thing there's generally an intermediate step between producing a small number of doses in "the lab" and real mass production, where you figure out how to efficiently and safely produce mass quantities.

"A chimpanzee cold virus was modified to carry Ebola genetic material conferring protection against the Zaire strain of Ebola."

What could possibly go wrong!

I don't have access to the complete article, so I have to guess. The virus have many parts. They probably copy one of the proteins of the surface of the Ebola virus in the flu virus, not the main infectious code. So it "looks" like an Ebola virus, but acts like a flu virus and only give you a mild flu.

The containing Wikipedia article the chimpanzee virus was attenuated, and that it doesn't replicate in humans, evidently either from that, or the modification (https://en.wikipedia.org/wiki/Ebola_vaccine#cAd3-EBO_Z).

This sort of vaccine engineering is well understood. The very step of substituting material tends to make the virus non-viable outside of the specialized environments in which it's produced, e.g. they've perhaps knocking out something essential for its normal function in chimpanzees. In a presentation I found from obvious Wikipedia pages they showed how they chose the starting virus out of a large galaxy of candidates, it's safe to bet without further examination it's not very bad for chimpanzees or us, to make development safer and easier.

The genes that code for Ebola glycoproteins (proteins with sugars) or critical, outward facing and therefore immune system alerting, parts of them, can't get very far without the rest of the Ebola virus payload.

At a very simple level, view it as poking at the immune system with a stick who's end is shaped in the way you want it, have with some precision engineered it. The immune system is going to react if you've done it right, you do expect some fevers and such in some people, but no more.

"Fortunately" Ebola is ultra lethal to all primates, so animal models are easy to find, and it could be thoroughly tested on them before trying it on humans.

Looks like I was right: https://news.ycombinator.com/item?id=8411674 -- not even two months, and we're almost there.

Pharma research tends to speed up when diseases stop being "the poor's own problem".

This clinical trial was run in August, before anyone had contracted Ebola outside of Africa (and before the comment you linked to).

Reply on news.ycombinator.com