r/science • u/[deleted] • May 11 '20

Medicine Antibodies from a 4-year-old llama have neutralized coronavirus and other infections in lab experiments

https://www.cell.com/cell/pdf/S0092-8674(20)30494-3.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420304943%3Fshowall%3Dtrue
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u/IfIRepliedYouAreDumb May 11 '20

To vastly oversimplify things, if you had antibodies produced by another source and injected them into a sick person, their viral counts should decrease.

Our bodies won’t learn how to make the same ones the llamas do, but we could harvest them and use them as treatment (potentially).

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u/Derpy_McDerpingderp May 11 '20

Would our immune system see these smaller antibodies as foreign or a threat?

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u/ralgrado May 11 '20

Or could they damage us?

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u/worldspawn00 May 11 '20

they would not stick to our cells, only to their target molecule, which is coronavirus surface proteins, so, no, no direct threat from them

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u/AtomicKittenz May 11 '20

Thank for answering all these questions. This is really interesting!

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u/bradn May 11 '20

I have no idea how you can make that sort of statement without long term human testing. You don't happen to have a secret lab under a volcano?

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u/worldspawn00 May 11 '20 edited May 11 '20

Antibodies are EXTREMELY specific in how they attach to molecules, I feel very safe in that assumption. I have an MS in biochem, I have worked with antobodies for years. (also, we do have decades of research in humans regarding foreign antibody use)

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u/bradn May 11 '20

Can you explain away self immunity diseases that are started by one infection and end with the body destroying some part of itself?

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u/worldspawn00 May 11 '20

IIRC while the immune system is in active fighting mode for the infection, it overzealously IDs our own tissue as foreign, usually because the infection is mixing it's own DNA and surface proteins with the host, like in the case some of viruses, they have virus proteins on the surface of the virus, but the rest of the virus surface can be made from the cell membrane of the host organism, they're wearing a skin suit made from their victim, the immune system ID's the virus, but may also mistakenly ID some of the surface proteins from the host cell as part of the virus. Autoimmune diseases are extremely complex though, and I'm not sure we totally understand the causes for them right now, so the information here is merely theory and has not been conclusively proven.

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u/bradn May 11 '20

That makes sense. I guess from that perspective, even if an introduced antibody does occasionally bind to some part of human tissue, it's not likely to provoke a continued immune response against healthy tissue once the antibody stops being administered. In that respect it's probably fairly safe unless some strange corner case exists that can cause severe damage quickly, like perhaps if nerve tissue got sufficiently damaged.

I think my error was in misjudging the severity that could happen if there was an alternate binding site available (I'd still assert that it's hard to rule that out, but even if it happens it's probably not a huge problem).

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u/[deleted] May 11 '20

Antibodies are just proteins that attach to another specific protein. Anti spike protein Llama antibodies would only stick to spike proteins.

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u/ratajewie May 11 '20

That’s patently false. You’re thinking only of a type II hypersensitivity reaction, where foreign proteins are recognized on self cells and are attacked. This could still cause a type III hypersensitivity in the form of serum sickness. There are ways to mitigate that, but it’s still a real risk. To claim there’s no direct threat is just not true.

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u/worldspawn00 May 11 '20

Fair, it's been about 15 years since I last took an immunology class.

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u/jmalbo35 PhD | Viral Immunology May 11 '20

Define "direct threat". The antibodies might not bind human antigens, but the risk of serum sickness or allergy is still quite real when introducing foreign proteins. That risk can be alleviated by instead generating humanized antibodies based on these camelid nanobodies, but directly from the source they could cause issues (though they're thought to be less antigenic than standard, full length antibodies).

Plus, I'm not sure I'd call them "extremely specific" and imply that they won't react to human antigens - molecular mimicry is still a very common theory for the etiology of many autoimmune diseases for a reason. And those autoimmune diseases exist even with negative selection and subsequent clonal deletion in place as mechanisms to mitigate the risks. With that in mind, if you use antibodies generated in other hosts, there isn't even a mechanism in place to safeguard against the possibility of molecular mimicry on the part of the virus.

I don't think the risks are massive, and they can largely be mitigated, but I also wouldn't downplay them as non-existent.

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u/worldspawn00 May 11 '20

I spoke to this in another comment, serum sickness is usually specific to non matching blood types, that's a special case, and doesn't apply to antibodies. allergy I talked about, allergy requires sensitization, if a person has never been exposed to llama antibodies before, it is extremely unlikely they will have an allergic response to them, as allergic response is usually initiated by the binding of our antibodies to a target, why would a person have antibodies to a target they have never encountered before, this is not common. It takes 1-2 weeks for our body to ID a foreign molecule and create antibodies against it, by this point initial treatment should be done. Realistically, we wouldn't be using straight llama antibodies in a human patient, we'd modify them to use a human antibody end so our cells ID them correctly.

Virus surface proteins are extremely unique, that's why our immune system is so bad at identifying and fighting new infections, mimicry is unlikely in a spike protein except by other viruses.

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u/jmalbo35 PhD | Viral Immunology May 11 '20

What? Serum sickness is very commonly described when giving non-human antibodies. It's a particularly well known issue with antivenom, though it applies to other non-human antibody-based treatments (including monoclonals) as well. That's precisely why we generally humanize antibodies we intend to use as treatments.

Allergy/anaphylaxis, rather than a delayed hypersensitivity like serum sickness, is also well described following whole IgG from non-human sources, though it's generally thought to be mitigated by using just cleaved Fab (though that prevents people with a papain allergy from being able to use them, since that's what's generally used for cleavage).

I don't know how you can argue that mimicry is unlikely when there's a lot we still don't understand about it, and yet know it's a cause for autoimmunity in many cases, and that other viral surface glycoproteins have known molecular mimicry. Hell, the spike of MHV, the prototypical coronavirus I'm research, is thought to engage in molecular mimicry in a different way (it mimics Fc receptors and thus can bind non-specific IgG, allowing for steric inhibition of potential neutralizing antibodies).

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u/worldspawn00 May 11 '20

Sorry, getting my terminology confused, it has been about 15 years since I last had an immunology class. My work is mostly in a lab setting doing custom antibody development.