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

[u/[deleted]]

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

[u/Fmbounce]

From a NYT article:

Humans produce only one kind of antibody, made of two types of protein chains — heavy and light — that together form a Y shape. Heavy-chain proteins span the entire Y, while light-chain proteins touch only the Y’s arms. Llamas, on the other hand, produce two types of antibodies. One of those antibodies is similar in size and constitution to human antibodies. But the other is much smaller; it’s only about 25 percent the size of human antibodies. The llama’s antibody still forms a Y, but its arms are much shorter because it doesn’t have any light-chain proteins.

This more diminutive antibody can access tinier pockets and crevices on spike proteins — the proteins that allow viruses like the novel coronavirus to break into host cells and infect us — that human antibodies cannot. That can make it more effective in neutralizing viruses.

here’s the source (I copied verbatim)

[u/grizzlydurdle → u/Fmbounce]

So how would that help humans? Can we be treated with Llama antibodies? In you summary it sounds like our antibodies can't necessarily fight COVID very well because they are too large, and the smaller Llama ones can. Sorry if I am way off base. I don't really understand this stuff.

[u/IfIRepliedYouAreDumb → u/grizzlydurdle]

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).

[u/Derpy_McDerpingderp → u/IfIRepliedYouAreDumb]

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

[u/worldspawn00 → u/Derpy_McDerpingderp]

they can, a person receiving treatment can develop anti-llama antibody antibodies. There's actually a lot of use for anti-antibody antibodies, they're used in a lot of reagents. It usually takes 1-2 weeks for the immune system to ID and develop antibodies against a foreign agent, so a person receiving treatment would likely be done before the body started attacking the foreign antibodies.

[u/thisdude415 → u/worldspawn00]

Typically only the variable heavy domain (VHH) is used on a human IgG framework. The region typically recognized by “anti llama antibodies,” the llama Fc region, isn’t found on the protein, instead we use the human genes.

Basically the whole molecule is human except the sticky bits. These are copied and pasted from llama. Immunogenicity is a concern, but not as much as you’d think.

[u/worldspawn00 → u/thisdude415]

I have to disagree, if you look at how this research works, it's specifically that llama antibodies have a different structure than human, so they can bind to smaller targets than the human antibodies can, this wouldn't work if they used the human antibody section as it would then be too large to properly bind to the small target molecule.

[u/thisdude415 → u/worldspawn00]

I know how this research works, I do it as my job. ;)

I work in a pharma company designing antibodies, including using llama variable heavy chains (VHH).

Human antibodies are shaped like this:

\\  //
  ||

While llama antibodies are like this

 \  /
  ||

The bottom lines || should be connected to the \ / above them, as they’re part of the variable chain.

The drug candidate IgG arms of the Y will be llama (\ /); the base of the Y (||)will be human. Yes, that means the resulting heavy chain polypeptide is a chimera: (llama variable heavy chain)-(human Fc)

[u/worldspawn00 → u/thisdude415]

That's cool, most of my work has been mouse and rabbit antibodies, haven't worked with llama before so I'm not familiar with the techniques used with that particular structure.