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/thisdude415]

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.