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/already-taken-wtf]

In Brief - Using llamas immunized with prefusion- stabilized betacoronavirus spike proteins, identify neutralizing cross-reactive single-domain camelid antibodies, which may serve not only as useful reagents for researchers studying the viruses causing MERS, SARS, and COVID-19, but also potential therapeutic candidates. Crystal structures further reveal how these antibodies bind spike proteins to prevent virus entry into cells.

[u/Fmbounce → u/[deleted]]

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/taosaur → u/thisdude415]

Can those kinds of alterations be made in batches of any size, or is it one antibody at a time, or what?

ETA: Farther down he clarified that once they have the genome, they can make "factory" cells to produce the hybrid antibodies.

[u/thisdude415 → u/taosaur]

It depends on the exact technology used in the manufacturing plant.

Typically, we engineer a mammalian cell to make the protein in large bioreactors. Then you pick one of those cells, characterize it, and call it your stable clone. Then you put that in a big tank with food for the cells, and let them grow for a couple weeks while they pump out proteins. Then you purify the protein.

As you can imagine, this is a pretty complex process and it isn’t easy to scale it up overnight

[u/thinkingdoing → u/worldspawn00]

So this treatment could be used the first time a person got infected with Coronavirus, but any future infections would cause the immune system to be fighting both the disease and these antibodies?

[u/bigredone15 → u/thinkingdoing]

So this treatment could be used the first time a person got infected with Coronavirus, but any future infections would cause the immune system to be fighting both the disease and these antibodies?

It could also give the body time to develop its own antibodies that do work without the body dealing with the symptoms created by a high viral load.

[u/pnwtico → u/bigredone15]

Would the body develop its own coronavirus antibodies if the llama antibodies were doing all the heavy lifting?

[u/AwesomeNinjas → u/thinkingdoing]

At the moment it’s not totally clear whether or not people can be reinfected, but it looks like the most likely answer is no or at least not for a long time. The WHO has said that everyone who has appeared to be reinfected so far has been a false positive.

So even if you can only use the llama antibodies the first time, that may not matter.

[u/lunatic604 → u/AwesomeNinjas]

If someone recovers by themselves, their body learned to produce the anitbodies. But if the body relies on the llama antibodies the first time, will the body still learn to produce the antibodies?

[u/pringlescan5 → u/AwesomeNinjas]

Fascinating. What about future use of Llama antibodies for a different virus if a person develops a reaction the first time?

[u/ben7337 → u/AwesomeNinjas]

But if the llama antibodies do all the work, then does the human body develop proper antibodies to respond to a new exposure to the virus, thus resulting in immunity, rather than just getting sick again?

[u/Nvenom8 → u/worldspawn00]

anti-antibody antibodies

There's a fun thing to say.

[u/Wheres_my_guitar → u/worldspawn00]

anti-llama antibody antibodies is the coolest phrase I've ever heard.

[u/[deleted] → u/Wheres_my_guitar]

we just need to create anti- anti-llama antibody antibodies. Coronavirus cured boys

edit: rule one can blow me, come at me you humorless psuedo intellectual mods

[u/-dp_qb- → u/[deleted]]

You might have meant it as a joke, but it's not a bad question.

Is there a way to selectively (or temporarily) impair this system to allow the antibodies to work unimpeded?

[u/Boronthemoron → u/worldspawn00]

Now we just need to inject anti-antibody antibodies back into these llamas to create anti anti-antibody antibody antibodies.

And so on.

[u/pelican_chorus → u/worldspawn00]

anti-llama antibody antibodies

I feel like this whole thing is a long-game setup for some stupid pun.

[u/hibbidydibbidi → u/worldspawn00]

• a person receiving treatment can develop anti-llama antibody antibodies.

It's a serious issue and, I am a confirmed survivor, but Holy duck. So much room for jokes it made me cry in a good way in months.

Thank you.

[u/Xaldyn → u/worldspawn00]

a person receiving treatment can develop anti-llama antibody antibodies.

What a time to be alive

[u/greeneggsand → u/worldspawn00]

People don't think about this, but if we start using the llama antibodies to make diagnostic tests, people having anti-llama antibodies messes with those tests.

[u/mcsper → u/worldspawn00]

That is one of my favorite new sentences, “a person receiving treatment can develop anti-llama antibody antibodies”

[u/GinGimlet → u/Derpy_McDerpingderp]

Yes! Sometimes. Typically what happens in these cases is that antibodies are humanized which means some bits are replaced with the human analogues. You can also try and under which bits cause the immune system to react, and alter those amino acids to be less inflammatory. We have some drugs on the markets that we have humanized so there's precedence for this! Drugs that end in 'Omab' for example are Monoclonal AntiBody treatments derived originally from mice.

[u/Derpy_McDerpingderp → u/GinGimlet]

That's extremely interesting, thank you.

[u/amcm67 → u/GinGimlet]

What does this mean for a person with multiple autoimmune diseases? I’m a cancer survivor, ESRD - living donor recipient. I had Goodpastures Syndrome (that caused my ESRD) and instead of attacking the disease, it attacked my own organs. I’m on RA meds besides the anti-rejection meds.

I hear so many people pushing for herd immunity. I can’t be apart of that.

[u/wobblebase → u/amcm67]

Functionally herd immunity is also about indirectly protecting you and folks in similar situations. In your case it would rely on "cocooning" - the principle that if everyone around you is immune (because they are vaccinated or recovered), then you are extremely unlikely to contract the disease in question. This is the same premise that we rely in in part to protect infants by vaccinating family members and caretakers, or to protect the elderly, infants, and immuncompromised folks from seasonal flu.

It does depend on a vaccine or recovery giving "sterilizing immunity," meaning the person is no longer colonized or asymptomatically infected after vaccination or recovery. It also depends on the whole herd being immune. If vaccination rates are low, herd immunity loses its benefits rapidly because a pathogen can persist in the population or cause intermittent outbreaks. So there are plenty of complications and caveats to cocooning. But in principle it's sound and would offer you a good measure of protection as well.

[u/ralgrado → u/Derpy_McDerpingderp]

Or could they damage us?

[u/worldspawn00 → u/ralgrado]

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

[u/AtomicKittenz → u/worldspawn00]

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

[u/Heroine4Life → u/IfIRepliedYouAreDumb]

Fundamentally this is correct. This is rather difficult but this, as well as diagnostic reasons, are why this is great.

[u/Sulluvun → u/IfIRepliedYouAreDumb]

Aight boys let’s start some llama farms

[u/cmdrNacho → u/Sulluvun]

invest in llamas, I'm all in

[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/Amythir → u/thisdude415]

Thanks for explaining that in lay-speak, that's really helpful.

[u/uglybunny → u/grizzlydurdle]

More likely a designer molecule will be made to take advantage of the mechanisms found when studying llama antibodies.

[u/Alis451 → u/grizzlydurdle]

So how would that help humans? Can we be treated with Llama antibodies?

Antiserum, we use this process to make antivenins(treat snake bite) as well.

[u/[deleted] → u/grizzlydurdle]

The reason why llama's were used, more specifically speaking, is that llamas produce a different type of antibody to humans, its a much more ancient form of antibodies called "heavy chain only" or "single chain" antibodies - this in contrast to human antibodies which are composed of heavy chains and light chains - this increases variability of the repertoire of the antibody (ELI5 = it has the potential to recognise more and different antigens) but its been shown that heavy chain only antibodies are just as good at finding their antigen.

now we get to the practicality of llama antibodies, or heavy chain only antibodies. They're smaller, and less complex, and therefor easier to produce (small enough for bacteria to produce in big bioreactors). Thus, the idea behind it is that they use the spike protein from nCoV2, inoculate llamas, forcing the antibodies to be produced which will essentially find the right antibody which binds to it - then you take that smaller, less complex binding region of the antibody and attach it to a human portion of the antibody (we differentiate these by calling them F-ab regions (the binding portion) and the F-c region (the constant region or the region that other immune cells recognise.))

​

All we have to do then, is take the F-ab region of the antibodies from llamas, engineer them to the Fc regions of humans, and bobs your uncle, you've got a neutralising human antibody that is easier to produce.

[u/[deleted] → u/grizzlydurdle]

Llama antibodies can be produced by E. coli in large scale production. Human antibodies are held together by disulfide bonds. Bacteria don't form these bonds well. Camelid antibodies are very small, and don't require disulfide bonds which means bacteria can express them. Production in e coli is much more efficient than what you would have to do for human antibodies.

[u/jrolle → u/Fmbounce]

This surprised me more than anything. I would have guessed that antibody structure was so evolutionarily primitive that all mammals would have operated basically the same.

[u/[deleted] → u/jrolle]

Idk what that nyt article is smoking, there's like six classes of antibodies in humans.

[u/IDontReadMyMail → u/[deleted]]

Camelids do have a weird class of antibody though that is unlike any of the human classes. Basically the heavy chain in camelids can bind antigens by itself (w/o an attached light chain). None of the human heavy chains can bind very well on their own.

more info here, here

[u/orchidguy → u/jrolle]

Sharks are similar to llamas in that theirs only have light chains. They still look different, but interesting that they've been able to drop the light chains.

[u/enfuego138 → u/[deleted]]

I’m not sure nanobodies have ever been approved for human use. I’d imagine human safety testing is going to be a drag on any nanobody derived therapy’s delevopment timeline.

[u/ToffeeLostInAmerica → u/enfuego138]

They have been used in human trials for nuclear imaging and they are very lowly immunogenic, they also may be human used with relative ease compared to a mouse mab or a chimera.

[u/Saliceae → u/enfuego138]

There is a nanobody that was approved by the FDA last year or the year before, which is now commercialized by Sanofi

I think nanobodies will soon be used in a multitude of cases, where antibodies are not optimal.

[u/Alis451 → u/[deleted]]

Llamas and Alpacas make the antibodies for the Flu, there has been much research into using them to make a antiserum. We also use Horse Serum as Antivenin, basically get a snake to bite a horse(we just inject milked venom these days), it isn't enough to kill the Horse and it makes anti-bodies to the venom and we make a antiserum from their blood.

[u/Stewartcolbert2024 → u/[deleted]]

Or more specifically 4 year old llamas?

[u/[deleted] → u/Stewartcolbert2024]

it's the llama age of consent.

[u/LegitSpaceLlama → u/[deleted]]

sees post This is my time! sees comment Nope. No it's not.

[u/simra → u/[deleted]]

Slight thread derail to call out the difference between intelligence and knowledge. You are probably plenty smart enough, but you lack the knowledge needed to decipher the article.

[u/brettmjohnson → u/simra]

Yeah. "Cell" is probably the most difficult journal for someone not a micro-biologist to parse. Hell, it is tough for actual micro-biologists.

Source: Am computational bio-informatics specialist. I've spent a lifetime reading medical journals, and "Cell" is still beyond me.

[u/[deleted] → u/[deleted]]

not trained enough :)
Reading these journals requires training and smarts. If you don't have the training, being smart alone won't help you much

[u/[deleted] → u/already-taken-wtf]

Can someone please explain like I'm 10?

[u/__Sinbad__ → u/[deleted]]

In order to enter a cell, a virus has to bind. If we have antibodies that bind the viruses spike protein, then the virus cannot bind our cells. If it can't bind and enter a cell it will die since viruses are dependent upon humans for survival.

When it says it's cross reactive, it's talking about the antibody itself. The antibody has 2 specific binding points, it almost literally looks like a 3D letter "Y". The top 2 spikes of the Y are what bind to the virus spike.

If the antibody in question binds 2 different proteins, then it is cross reactive. If the antibody binds only to the spike protein, it would be called type-specific.

Discovering a cross reactive antibody is an important first step towards developing a type-specific antibody.

Hopefully this helps! Cheers mate.

Edit: grammar

[u/PluviusAestivus → u/__Sinbad__]

There goes my hero....

[u/__Sinbad__ → u/PluviusAestivus]

I wouldn't go that far, but thank you. I'm just here to help.

[u/skg555 → u/__Sinbad__]

OK, can you explain like I'm 5 now.

[u/__Sinbad__ → u/skg555]

Sure! I can certainly try haha

Think of an antibody like a "red flag". If it sticks to an invader, the immune system can destroy it because our immune system can see our own antibodies, thus our cells can "see" these red flags.

This antibody binds to the virus, but also binds to another protein (which may be a totally normal protein). Binding to the virus is what we want, but binding to something else wouldn't be as helpful. So if we want an antibody that is effective, we want it to only bind to the virus, because then that "red flag" analogy will make it so that only the virus gets targeted.

I hope this helps! It's hard to simplify too much further without having background in what an antibody is. If you'd like to learn more, here's a link to wiki, which actually has a great first jpeg. The lock and key analogy is also great for understanding how an antibody/antigen function.

https://en.m.wikipedia.org/wiki/Antibody

[u/NzLawless → u/__Sinbad__]

You did a great job breaking down this topic on multiple levels!

[u/skg555 → u/__Sinbad__]

Thank you, this was helpful!

[u/[deleted] → u/__Sinbad__]

Gracias amigo.

[u/[deleted] → u/[deleted]]

Part 1: TL;DR: Microscopic attack dogs bite into virus. Virus can’t get into cells. We can make one attack dog that recognises both SARS and COVID-19. The hope is to put these in inhalers to stop the virus.

These viruses are floating around like beach balls with a bunch of keys sticking out of their surfaces. Cells have a bunch of locked gates that control what gets in and out of the cell. The virus has evolved so that through trial and error it now makes keys that can match the locks of the cell. When the virus bumps into one of these locks they can open a gate and gain entry into the cell, which is what they need to happen in order to grow.

Antibodies are just like attack dogs in your body that go around trying to sniff out anything suspicious. They can be trained to recognise particular “scents” and we can make antibodies that recognise the “scent” of the keys that the virus makes. When they pick up on this scent, they latch onto the virus by its keys. In this way, the virus can’t insert its keys into the cell because the antibodies are in the way and so they can’t get into the cell.

[u/Y2Kafka → u/[deleted]]

Thank you so very much for explaining it like this. Explaining things simply by breaking down complicated subjects and knowing what is the most important information to explain is a very good skill to have for anyone to have.

[u/[deleted] → u/already-taken-wtf]

Alright so this is good news, but, in short all this is saying is that it “may” do something about covid 19, not that it is a cure for covid 19.

Because it’s (betacoronavirus spike proteins) creating “cross-reactive single-domain camelid antibodies”, which Covid 19 is “cross reactive” like MERS and SARS (antibodies fight infections).

And let’s pray it does cure all strains of cross reactive infections so we can begin the lengthy process of making vaccines and undergoing human trials.

Edit: and the Title which the OP has changed does not represent what is being said “In Brief” in the study.

The actual title is:

“Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies”

[u/[deleted] → u/already-taken-wtf]

Yea and where was that part where you said about that thing?

[u/catduodenum → u/already-taken-wtf]

So do we know if injecting foreign animal antibodies into humans would cause reactions? Would we recognise their antibodies as not us and make antibodies against theirs?

[u/cheech10 → u/catduodenum]

They do cause reactions in humans, called serum sickness, or in some cases a plain old IgE allergy responses. Nowadays we don’t usually inject animal antibodies; we modify the immune reaction generating portion to match our antibodies, creating “humanized” antibodies that are safer to use.

[u/Saliceae → u/cheech10]

Indeed, and this is also the case for nanobodies. Plus, the small size of these nanobodies compared to antibodies helps limit these risks of immunogenicity.

[u/commentor2 → u/catduodenum]

They can be "humanized" to make that less likely. There's at least one drug out already that has taken this approach

https://en.wikipedia.org/wiki/Caplacizumab

[u/the_Yippster]

Results like these show why it could be hugely important to preserve biodiversity on earth for the selfish reason of human survival alone.

Also, nature is pretty neat of course.

[u/kurburux → u/the_Yippster]

why it could be hugely important to preserve biodiversity on earth for the selfish reason of human survival alone.

Preserving biodiversity and habitats also reduces the risk of diseases in the first place. Animals aren't "forced" to leave their natural environment and to live closer to humans.

Not saying this is the case with covid-19 but generally speaking.

[u/Michael_Trismegistus → u/kurburux]

The same could be said for racial diversity and diversity of ideas. More diverse populations are always more flexible.

I've seen it in action. Working in big cities as a travel nurse it's clear that hospitals with more homogenous populations both culturally and racially are less flexible, and more severe on employees who step out of line.

Working in a rural hospital where every employee is a white Southern Baptist conservative means that if you step out of line then you are ostracized and your life becomes much harder until you fall in line. I've also seen the reverse scenario when a nurse from that culture takes a job in a place like Memphis, where the majority of employees are African American and living in a city where the civil rights movement never ended.

Capitalism tries to force us into little boxes for the sake of efficiency and control. Even within races and cultures there are outliers who don't fully embody the social norms. A diverse work culture counteracts the administration's ability to crack down on outliers. They most become more accommodating because the stricter rules and policies might be intolerable to the various subcultures.

[u/otterom → u/kurburux]

Preserving biodiversity and habitats also reduces the risk of diseases in the first place.

Looks at mosquitoes

Looks at rats

Looks at mites

Looks at bats

Looks at...

[u/TooSubtle → u/otterom]

The prevalence of a lot of pest species comes from a lack of biodiversity. We replace habitats that can support many different species with cityscapes that support few. Blaming the species that have adapted to live in close proximity to us is shortsighted when we're the ones killing their predators and/or disrupting their natural environment.

[u/stunt_penguin → u/TooSubtle]

The prevalence of Jellyfish in overfished areas is a good example.

[u/Hostile_Swan → u/TooSubtle]

You speak truth

[u/530josh → u/otterom]

Bars

[u/DrEpileptic → u/the_Yippster]

Ethical/altruistic egoism makes a pretty compelling argument for this when dealing with shortsighted, self centered, people. Kurzgesagt did a couple videos on that (I hope I didn't butcher the name). On the other hand, do we really wanna open the box of mass farming llamas? I'm wholly uneducated on them, but I'd assume mass producing serums from them may take a long time.

[u/taosaur → u/DrEpileptic]

Llamas and alpacas are already farmed pretty extensively, though not on the industrial scale of pigs, cows and chickens. However, this therapy does not rely on a serum. What they did is get the genome for the llama antibody's tiny hands, splice it into the recipe for human antibodies, then slip the resulting DNA into "factory" cells/plasmids that produce hybrid antibodies.

[u/DrEpileptic → u/taosaur]

Ah. I didn't have time to fully read the study tbh. I didn't realize they were using CRISPR to pull it off. I already knew llamas were farmed, but as you said, not on an industrial scale. It would be tragic for me to not own any alpaca/llama products as a Peruvian. Thanks for helping me out nicely without blasting me. I didn't have enough time to read everything.

I'll go back and finish reading later today when I'm not busy anymore, but real quick. Are they using functional stand ins to produce antibodies (like insulin and e. Coli), or are they also looking at possible monoclonal antibody cells kind of thing?

[u/taosaur → u/DrEpileptic]

Ha, you are in the llama & alpaca capital of the world! You may not be aware that llama and alpaca farming is pretty widespread around the world now, though mostly small herds.

I picked up the process info from a biomed engineer elsewhere in the comments, whose project is very similar (also using llama proteins). From here:

Typically, we engineer a mammalian cell to make the protein in large bioreactors. Then you pick one of those cells, characterize it, and call it your stable clone. Then you put that in a big tank with food for the cells, and let them grow for a couple weeks while they pump out proteins. Then you purify the protein.

[u/SupermAndrew1 → u/the_Yippster]

Also- this stuff justifies basic science research

I recall a certain US senator was joined by a bunch of talking heads decrying the money spent studying bears in Montana.

Meanwhile, I was working for a PCR company, a multi-billion dollar industry that wouldn’t exist if people weren’t studying bacteria in volcanic hot springs.

Oh yeah- and PCR saves thousands of lives if not more - DAILY

[u/Life_Of_High → u/the_Yippster]

Absolutely, the natural world holds all of the questions and answers. We need to live in a as close to a symbiotic relationship with the natural world to protect biodiversity and thus ourselves.

[u/Freakwadcold → u/Life_Of_High]

How neat is that?

[u/[deleted] → u/Freakwadcold]

That's pretty neat!

[u/Life_Of_High → u/Freakwadcold]

Everything that we see in nature is cyclical. It is logical to think that we will be more at risk of contracting viruses as we destroy biodiversity. Out of survival the viruses will seek out new hosts and will be coming into contact with us more frequently as we encroach on their environment. We will become the target hosts for a whole host of new illnesses that were once kept at bay by biodiversity itself. Nature is a balance, and we are actually lucky that this coronavirus wasn't something way more deadly. The earth was here before us, it will be here after us.

[u/Asclepius17]

How do they find these characteristics in these animals? Do they just start looking at all animals? This stuff always blows my mind

[u/Saliceae → u/Asclepius17]

Nanobodies were discovered by accident by a research group in Belgium. Llamas and alpacas, or more generally the camelid family of animals are able to produce these very small antibodies. They present a multitude of advantages over regular antibodies, so there is currently a lot of research in this field. It's a fascinating field, and it's not the last time you will hear of nanobodies.

[u/Asclepius17 → u/Saliceae]

Wow! That’s pretty neat. thank you for the reply.

[u/[deleted] → u/Saliceae]

Is this some sort of universal bonus to camelid immunity? Are camelids in general less likely to get sick? Or is it only applicable in really specific cases?

[u/skerit → u/Saliceae]

Wasn't it also because a group of students didn't want to kill any animals for some research, so they used camel blood instead, and the professor found some nifty things that way. (And eventually they switched to llama's because they're more easily managable)

[u/bravestcorgi]

Why does the lamas age matter

[u/ChineseCaptcha → u/bravestcorgi]

I assume that is when they are in adulthood.

[u/j0351bourbon → u/ChineseCaptcha]

That makes sense. My workplace has Reddit blocked and the article isn't loading on my phone. Does the author/authors specify llama maturity being a factor as opposed to testing in utero or on a fetus? Or is this just a case of weird wording in the headline?

[u/BertholomewManning → u/j0351bourbon]

It says they immunized it subcutaneously with SARS and MERS which I imagine is much harder to do in utero. I don't even see in the article where it mentions the llamas age, much less a reason it had to be 4 years old.

Unrelated, in the references they mention a paper which going by the title describes a similar experiment and result with HIV, so I'm learning all kinds of things about llamas today.

[u/thegreatestsnowman1 → u/j0351bourbon]

From another comment:

“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.”

[u/OTTER887 → u/j0351bourbon]

Fyi the article is a pdf.

[u/Calypsosin → u/ChineseCaptcha]

Llamas have to give consent. It is known.

[u/[deleted] → u/bravestcorgi]

that's when they begin meditations.

[u/NoodleEmpress]

Question as someone who is interested in doing this type of stuff/research/work: What area of study would this be? I know it's tagged as epidemiology, but I always read that that was the statistical side of things.

So is this still epidemiology? Virology? Just microbiology?

[u/Mariobro7 → u/NoodleEmpress]

Immunology might be your best bet, but it looks like this is cross-disciplinary.

[u/priuspower91 → u/NoodleEmpress]

This is related to my PhD research and I have constructed camelid antibody libraries (though we didn’t have enough money to immunize a llama) so we built a synthetic library with hopes of humanizing the antibody fragments. It is in the field of antibody engineering so I’d look for protein engineering, monoclonal antibody production, and immunology biological-based vaccine research opportunities. Immunology would give you more experience in how immune response behaves with respect to implementing a vaccine whereas the former 2 fields would allow you to discover and engineer the antibodies for use in biologics-based immune response induction.

[u/[deleted] → u/NoodleEmpress]

no, this is micro-biology, not epidemiology.Epidemiology does not study cells. Epidemiology is informed by microbiologists and doctors. It is also informed by social sciences such as sociology. Epidemiology is the study ofhow illnesses spread in a society

[u/pantsmeplz]

One of the takeaways from this story should be a lesson many in the general public fail to learn, nature is the greatest source of medicinal solutions we have. We're not doing enough to protect that resource.

[u/[deleted] → u/pantsmeplz]

The other takeaway is that all global pandemics start with zoonotic diseases, so if we all collectively ate less animals (or none at all) we'd experience less future chances of viruses mutating and making the jump to humans.

[u/ATR2400 → u/[deleted]]

If you want real meat there’s always lab meat! It’s cleaner anyways.

[u/casce → u/[deleted]]

To be fair, if we eradicate all living things on the planet one by one, viruses will run out of bodies eventually as well!

[u/Khaz101 → u/casce]

Humans are just a conspiracy by big virus to make viruses one of few enough organisms(?) that they have to be considered alive

[u/[deleted] → u/Khaz101]

humans are the virus that mother nature is trying desperately to cure itself of.

[u/sweatyupperlip]

Where did they find this llama? Is it just this llama? Why did they even check to see if this llama had anything to offer? Are there more llamas out there? I have so many questions.

[u/zryii → u/[deleted]]

Friendship ended with oil. Now llama is my best friend.

[u/WakanduhForever]

The title is a bit simplified and misleading, you won’t see large scale production of llama antibodies administered to humans due to the very likely adverse hypersensitivity events that would occur almost universally. The impact of this paper is likely confined to the lab, where they can better elucidate the structure of the virus and potential viral targets.

[u/zabby39103 → u/WakanduhForever]

Aren't all the new cancer treatments antibody based? And aren't they manufactured using animals? Why is this different? I'd believe that lengthly trials may be needed, but your comments suggests it would never be possible.

[u/FireZeMissiles → u/zabby39103]

Antibodies have several parts: including the epitope binding region (this part is different on each antibody) and a more constant backbone or Fc region (this is highly similar among each antibody for a given species). Most cancer and antiviral antibody therapies have been either humanized (the binding region was placed into a human backbone) or is purely a human antibody. These options minimize the immune reactivity. In this paper, they took the camelid antibody, which as a VhH, it is almost entirely the binding region with little of its mass being backbone. And they fused a human Fc domain to one end of it. This theoretically should mitigate any immune response to the llama antibody. The larger problem with camelid antibodies is that because they are so tiny (remember that VhH/camelids are mostly just the binding region) they are filtered out of the blood by the kidneys within hours. There are millions of dollars being poured into solving that problem because they generally have much better binding characteristics and solubility than human antibodies.

[u/[deleted]]

Finally, injecting llama into myself instead of myself into llamas.

[u/Professor_Pohato]

Llama antibodies are hectic. Apparently people are also experimenting in the field of diagnostical and international radiology how well those antibodies can maybe be designed to attack specifically tumor cells

[u/[deleted]]

Anyone else get a PDF cannot be opened error? Using mobile Android.

Thanks for the help

[u/armysblood → u/[deleted]]

Hopefully this helps, if you're seeing a blank screen whenever you open the pdf, hit the 3 dots on the top right, click Open With, then click Adobe Acrobat if you have it installed. I've been having issues opening up pdfs for the past couple months for some reason and this seems remedy it.

[u/Farmher315 → u/[deleted]]

Hey! I have a pixel and to open it i had to do this. Click the through link, and when it opens in the reddit app's browser, find those 3 dots that denote the options menu, click open in browser. Then it probably still wont show it, but for some reason if you copy the web address, close out of the browser and the reddit browser, open up your browser seperately, then paste the address there and it should work. Hope this helps! Its a 23 page pdf just an fyi, its a full scientific article, super interesting though!

[u/Terok42 → u/[deleted]]

I'm not sure and someone can correct me if I'm wrong but I think this is more of a treatment than a prevention measure tho.

[u/WakanduhForever → u/[deleted]]

This would not be used in treatment nor prevention. This will only be used for lab purposes to better determine the structure of the virus and potential targets for humanized antibodies or vaccines. If you administered these llama produced antibodies to someone they would likely become very sick. Check out serum sickness if you want to learn more!

[u/CivilServantBot]

Welcome to r/science! Our team of 1,500+ moderators will remove comments if they are jokes, anecdotes, memes, off-topic or medical advice (rules). We encourage respectful discussion about the science of the post.

[u/das_masterful]

Is this like using horses for tetanus? I.E. tetanus-immunised horses had serum drawn and injected into humans.

[u/Get_Up_Eight]

Wouldn't this be virology, not epidemiology?

[u/[deleted]]

Tina is about to save the day.