One wonderful thing that has come two US citizens being infected Ebola (and successfully treated for the disease) is *education* the general public is getting about this, frankly, 'scary' virus.
Im not talking about the bizarre nonsense/missed opportunity posted by Sanjay Gupta and his 'producer' Danielle Dellorto. Of course science bloggers have capitalized on this opportunity to educate people (its kinda what we *do*). But some journalists in main-stream-media, unlike Gupta and Dellorto, have taken a moment to speak to actual scientists working on Ebola/the technology to make the 'secret serum' the two US patients got.
How the experimental Ebola serum works (Warning: video link!)
Those stories featured Dr. Charles Arntzen, a National Academy of Science member with *decades* of experience using plants to help treat viral disease, and, Dr. Erica Ollmann Saphire, a researcher at Scripps who figured out what the anti-Ebola antibodies used in this therapy 'look like', and how they work. Im so excited these kinds of scientists, down and dirty scientists, are getting to talk about what they love.
But I dont think either of those articles really explain well how this therapy could *WORK*.
We really have two options:
1-- Two of the antibodies in this mix are 'neutralizing antibodies'. This means, these two antibodies 'stick' to Ebola in such a way, that the protein Ebola needs to use to infect cells, cant interact with the new host cell. Its like if you were about to play the violin, and someone put boxing gloves on your hands. Its not gonna happen.
2--One of the antibodies in the mix is non-neutralizing. "If it doesnt stop the virus, what good is it, eh?" you might ask. Well, antibodies are good for more than just neutralization. When a cell is infected with Ebola, it will produce Ebola proteins (duh). Proteins that are supposed to show up on the outside of the virus, will show up on the outside of a cell (of course, as the babby viruses bud off). Non-neutralizing antibodies can still help stop an Ebola infection by sticking to the outside of an infected cell. Covered in antibodies, an infected cell will either:
a) Die via getting blown up by the complement system: Complement dependent cytotoxity
b) Die via getting blown up by a Natural Killer cell (or alternative immune cell): Antibody-dependent cell-mediated cytotoxicity
That is how the serum *could* work. By killing infected cells, and preventing free virus from infecting new cells.
Thats how it *could* work.
That doesnt mean thats how it *did* work.
*If* it did work.
*If* the serum worked via #1, it seems like it would have taken at least 48 hours to see much of a result. The Ebola life-cycle is ~48 hours. So if viruses were getting neutralized, you wouldnt notice much of anything until the cycle was interrupted by the neutralizing antibodies. You would have 48 hours of new viruses being released, before they could be neutralized.
But according to Sanjay (warning auto-play video!!), Kent Brantly was feeling better within one hour of receiving the drug.
The only thing I can think of that would work *that* fast in this serum is "2a: Complement dependent cytotoxicity". It would be like hyperacute rejection of tissue/organ transplants-- antibodies would bind to Ebola infected cells, the antibodies would set off the complement cascade, and all those infected cells would be dead like THAT *snaps-fingers*.
... No yay. If you were in the midst of a full-blown Ebola infection, you would have LOTS of infected cells dying at the same time. You would FEEL LIKE CRAP. CRAAAAAAP. Remember those GMO tumor-killing viruses that Im always talking about? One of their side-effects is 'feeling like crap' because youve got a bunch of dead tumor floating around. I would expect a bunch of dead ebola cells floating around would have a similar effect.
... But Kent Brantly was feeling better within one hour of receiving the drug.
Look, I love technology, I love the idea of the Top Secret Serum, be we do not know if it helped treat the two US patients, and if it did, how.
There are still lots of bad things that could happen if it is rushed into patients without the proper trials. The antibodies could bind to some human protein and cause momentary autoimmunity. Depending on the target, this could vary in severity. The antibodies could bind to a TON of virus and mess up peoples kidneys. They could start complement mediated cell lysis and severe, if not deadly, immune activation in patients.
If you really fucking love science, you have to love the boring clinical trials, like putting the therapy into healthy people to make sure nothing bad happens (or something tolerably bad happens). You have to be able to temper the *chance* you might save lives during an outbreak, with the *chance* you might make things worse. Or, even though a treatment might look perfect on paper, you have to be able to admit that maybe, it might, perhaps... not do anything.
Fingers crossed scientists can get something worked out for the folks in Africa and the medical teams trying to save them. Fast.
Love how the NHS have magiced up a dose of ZMapp from the WHO, when all the doses were supposedly handed out already. In my head, the NHS and WHO were playing high-stakes 'swapsies', eg "You give us some ZMapp and we'll sequence the shizzle out of some ebola blood samples for you, get you some more full genomes... And we'll throw in a visit to the Tower of London for whoever couriers the dose over..."
"If you really fucking love science, you have to love the boring clinical trials"
Best quote in a science blog ever!
You outline the possible benefits of non-neutralizing antibodies to Ebola. I would urge caution as I can imagine some negative complications. A well known phenomenon in the Dengue world is called antibody dependent enhancement wherein a prior infection with a different strain of dengue causes non neutralizing antibodies to other strains. These non neutralizing antibodies increase the infection with other strains leading to more likely/severe disease. Surely this was a consideration made by the folks who developed ZMapp.
On a different note, I thought that Ebola and other enveloped viruses do not bud off and remained linked to host cells. This is important because you explained that this would be a mechanism by which non-neutralizing antibodies might tag infected cells for ADCC, NK CMI or opsonization. I would think that the relevant epitopes might be presented by MHC instead. IMHO.
Abbie Smith, today I first discovered your . . . endeavor to educate us on cutting edge science by providing the truth of things as you know it to be. I love it. Thank you very much.