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There is contradictory (~?) evidence in the literature that antibody responses against Ebola are effective in clearing the virus and protecting the patient. Some time ago, I wrote a bit about the literature on this in my blog (which you can find here) that one of the primary problems faced in developing an effective antibody response against Ebola is that antibodies may actually be hijacked by the virus in order to mediate entry (Takada et al). My question is, has this observation been supported? And, if so, how do more recent vaccines address / avoid this problem?

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    $\begingroup$ As far as I can see the link you reference does not support the idea that antibodies mediate Ebola entry. There was some speculation that this might happen, but I don't think there was ever much (if any) support for it (other than analogy with viruses like Dengue). In general, lab animal vaccine trials have shown that Ebola antibodies are pretty effective. $\endgroup$ – iayork Oct 21 '15 at 23:14
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    $\begingroup$ OK, I'm ready to be embarassed - I need to check on this and see if I may have referenced the wrong article ... or, I don't know... maybe I dreamed it. I'll look into it and repost later. $\endgroup$ – johntreml Oct 21 '15 at 23:55
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    $\begingroup$ iayork - I'm sorry, I cited the wrong article. The appropriate article is Takada et al - correction made with link in text above. $\endgroup$ – johntreml Oct 22 '15 at 0:00
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Although there are a handful of papers suggesting that antibodies can enhance Ebola infection, in practice Ebola vaccines seem to be highly effective both in animal models (e.g. Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses, VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain, Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus) and, probably, in humans (Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial).

If antibodies can enhance infection, how could vaccines protect? That's not as contradictory as it sounds. In general, antibody-mediated enhancement of infection only works under specific conditions. Even with Dengue, the poster child for ADE, it only occurs during a specific window of antibody titers and affinities. Ebola is probably much less adapted to needing ADE than Dengue, so it's likely that you'd only get ADE in a very narrow range of antibody titers, affinities, and perhaps targets. So if vaccines induce high titers, high affinities, and/or a particular set of antigenic targets, ADE may never kick in -- it may be a lab curiosity that isn't relevant in the real world.

(Alternatively, it may be an issue down the road, say if vaccine-induced immunity fades in a specific way that allows it. I don't know of any evidence suggesting this would happen, but I'm not an Ebola researcher.)

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  • $\begingroup$ --it may be a lab curiosity that isn't relevant in the real world. This is exactly what I have thought as well since reading the original article that brought it up, but with all the fervor to develop new vaccines, I thought it was both something to keep in mind when fast-tracking a drug as well as a question that newly published data might answer. Ultimately, these are the kind of data that make me pay attention because something novel might show up. $\endgroup$ – johntreml Oct 22 '15 at 20:47

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