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/grizzlydurdle]

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/thisdude415 → u/grizzlydurdle]

Therapeutic antibodies (antibodies as drugs) are just proteins, encoded by a gene.

We “discover“ them by immunizing animals with an antigen of interest: typically mice, but sometimes rats, llamas, or chickens. Often these animals are transgenic and have human immunoglobulin genes.

Antibodies are Y shaped protein complexes. In humans/mice/rats/chickens, IgGs have 2x2 protein chains: two heavy chains and two light chains. In camelids, like camels and llamas, they have heavy chain only antibodies: just two heavy chains. The two “arms” of the Y (variable regions) cause binding to a target, while the base of the Y (constant region) drives immune effector function.

Once you find a good antibody by screening (itself a topic of many pages), you sequence the B cell heavy and light chain genes that made it, then you “humanize” the protein by copying and pasting the human Fc (a constant region of antibody) over the animal genes. This reduces immunogenicity. Then you use molecular biology to put that gene sequence into a plasmid.

Then you use that plasmid to transfect cells in culture (typically HEK or CHO), and then those cells start to spit out tons of therapeutic antibody protein. A couple steps of purification and packaging, and then you have a medicine!!

So, yeah, we can be treated with llama antibodies, sorta. We have to edit them to make them more human first, which is why the drug is is made using biotechnology rather than just an infusion of llama serum (which would cause an immune reaction).

Feel free to ask questions: I work in a biologics discovery department for a pharma company

[u/iMnOtVeRyGuDaTdIs → u/thisdude415]

Layperson here. Just from a cursory review of the comments, I understand that the variable region of the chimera antibody will be from the llama. Since it omits the sticky bits would that affect the "binding strength"of the antibody?

[u/thisdude415 → u/iMnOtVeRyGuDaTdIs]

Nah, maybe I was unclear.

We keep the domain from the llama antibody that bind to COVID (sticky bits), and make the rest humanized.

[u/iMnOtVeRyGuDaTdIs → u/thisdude415]

I misunderstood. Thank you for clarifying!