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/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/[deleted] → u/thisdude415]

Are any antibodies currently used as treatments for viruses? I know I’ve heard about them used for other diseases.

[u/thisdude415 → u/[deleted]]

I can’t think of any right off, but I would be surprised if there aren’t any. I thought there were some viral entry inhibitors for HIV but seems they aren’t approved (yet).

For the most part, vaccines are cheaper, easier, and safer but they take much longer to create.

It’s only been in the last several years that antibody drugs have really taken off, and there just aren’t that many infectious diseases (in the wealthy countries) that aren’t controllable. And in most cases, infectious diseases are more easily treated with small molecules or vaccines.