Structural and molecular basis for Ebola virus neutralization by protective human antibodies

Ebola virus causes hemorrhagic fever with a high mortality rate and for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated following proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

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Why is it that structural / molecular immunologic studies always "may facilitate development of therapies and vaccines"?  Really??  How about looking at what the actual vaccines did in terms of eliciting sterilising immunity, or controlling viral load?

So nice work, but it characterises the mode of action of just two monoclonal antibodies from the spectrum of many thousand that would be involved in reaction to infection, and of the hundreds that are involved in vaccine responses, and the many in any single individual that would be involved in actual neutralisation of infectivity / ADCC / infected cell killing, etc.

What I’m getting at is that whole protein responses, in the context of live vaccine vector inoculations, are almost certainly more complex than anything that involves just these two antibodies, and elegant immunological / structural studies are a minor part of understanding the whole problem.

See on Scoop.itVirology News

2 Responses to “Structural and molecular basis for Ebola virus neutralization by protective human antibodies”

  1. uncoating Says:

    A combination of mAb100 and mAb114 protects macaques against ebola virus infection, even when administered days after a lethal challenge with the virus. In fact, mAb114 alone has this effect. See link below.

    Obviously, macaques are not humans, so no guarantees, but the point is that in this particular case – hopefully – it really may be that simple that a single antibody does the trick. That’s why it such an exciting study. It is certainly not an overstated claim by these authors that their structural work “may facilitate developments and vaccines.”. Anyone pursuing such antibody-based therapies against ebola virus should take note of their findings.

    • Ed Rybicki Says:

      Oh, sure, it’s interesting – but the fact remains that not one vaccine currently in humans has relied on structural work or deliberate design for its efficacy. Not one. I am involved in HIV vaccine work, and I think there is an enormous amount of hand-waving in that field about how “structure will solve the HIV immunogenicity problem” – whereas after years, it has not. It has helped explain things, sure, but solve them?
      I like that Abs can protect people against dread diseases like Ebola, I really do (see my posts on ZMapp on this site) – but I think that relying on one or two MAbs is not the answer. A potential therapy, sure, but not the answer – I think that lies in the vaccines already tested against Ebola, and in particular the VSV-EBOV live recombinant. Just my bias B-)

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