7 ms·

A key ingredient for a universal flu vaccine may come from llamas

184 points by broahmed 8y ago

darkerside 8y ago
> The genetic instructions for making the antibody were packaged up inside a harmless virus, which was then used to infect the noses of mice. That's interesting. I didn't realize gene therapy could be so localized.
- Nasrudith 8y ago
  Well every copy of the DNA doesn't make it into the germ-line and viruses generally infect differing types of cells in the first place.
- rubatuga 8y ago
  Yep, they usually use a pseudo virus that doesn't replicate, called an adeno associated virus. Check out this guys video on his own gene therapy for lactose intolerance : https://m.youtube.com/watch?v=J3FcbFqSoQY https://m.youtube.com/watch?v=J3FcbFqSoQY
- rotexo 8y ago
  Yep, adeno-associated virus (AAV) vectors seem very promising. Depending on the type of vector used, you can target the eye, joints, liver, lungs, etc. [1]. Relatively recently, the FDA approved the first AAV-based therapy for a rare retinal disorder [2]. Also worth checking out are some promising trials for treatment of severe hemophilia using AAV vectors [3]. These might end up being great, because the current gold standard treatment involves giving people regular injections of recombinant clotting factor protein, which is even more expensive than gene therapy. Plus, with gene therapy, you have one treatment that lasts a long time, versus having to get an infusion of the treatment regularly. [1] (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138125/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138125/) [2] (https://www.labroots.com/trending/drug-discovery/7533/adeno-associated-virus-gene-therapy-fda-approved-rare-retinal-disease https://www.labroots.com/trending/drug-discovery/7533/adeno-...) [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728634/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728634/
BariumBlue 8y ago
I know that cow antibodies are also generally more effective than human antibodies due to their increased length... Why specifically use lamas?
- craftyguy 8y ago
  The article mentions why.
- clort 8y ago
  llamas produce very small antibodies that can attack the parts of the virus that are further inside, and these parts do not mutate as often as the outer parts, which our antibodies generally attack. The outer parts mutate pretty quickly, meaning that any vaccine or treatment that we normally provide only works for a short time.
  - whatshisface 8y ago
    If the inside parts have more to do with the functioning of the virus (which is what one might guess from hearing that they are more conserved), could targeting them with antibodies bias viral evolution towards colds turning deadly as opposed to slight changes in their shell proteins?
    - WhiteSage 8y ago
      Evolution often makes viruses less deadly, as it wants to maximize dispersion, and killing the host is usually not a good strategy. They will probably just try to mutate to cover those inner parts of the shell proteins.
  - arkades 8y ago
    The really terrible pop-sci write-up says because the antibodies are smaller. The actual publication doesn't given a reason for using llamas. The rationale discussed doesn't hold together, either, since nothing in the study is about "small ab penetrating deeper." To quote the actual study: "Moreover, most vaccine-induced antibodies are directed against the highly variable head region of hemagglutinin (HA) and are strain specific. However, broadly neutralizing antibodies (bnAbs) targeting influenza HA have been isolated and characterized (8). Several bnAbs have entered clinical trials as therapeutic agents, but their use in influenza prophylaxis remains elusive because of the incomplete coverage against circulating human influenza A and B viruses, which necessitates administration of a bnAb cocktail, and the need for multiple, high-dose injections for protection throughout the entire influenza season. High serum bnAb levels are required because of poor distribution to the upper airways. We present an alternative strategy for long-lasting protection in which single-domain antibodies (sdAbs) (9) with influenza A or B reactivity are linked together into a multidomain antibody (MDAb) and expressed at the nasopharyngeal mucosa through the intranasal administration of a recombinant adeno-associated virus (AAV) vector (10, 11) encoding the MDAb transgene." Their whole point was to take Ab that target highly-conserved regions and link them together into a, let's call it, multi-tool ab that has a variety of ways of hitting highly conserved regions. Nothing at all about that approach suggests using "smaller ab" to "penetrate deeper." It's true camelids produce single-domain antibodies which are much smaller than the multi-domain antibodies humans use, but that wasn't the goal of the study: on the contrary, using peptide linkers to string together ab sounds like it accomplishes quite the contrary. I think the actual rationale is: "we wanted to string together a bunch of different antibodies to maximize the likelihood of our construction finding a target, and human ab are so big that if we string them together it'll be useless - so we strung together a bunch of small, highly targeted ab, whose final size will still be small enough to allow the multi-headed hydra to interact with viruses."
tw1010 8y ago
I can't bring myself to be in any way happy from reading stuff like this. We get articles like this every freaking day and probably only a fraction of them will ever get into production.
- garmaine 8y ago
  Only a fraction of them end up being repeatable.
  - noja 8y ago
    Those lucky fruit flies and llamas.
  - radus 8y ago
    Not my field, but based on what I know of the quality of research in this lab and the fact that it was published in Science, I would be very surprised if the results aren't very solid and reproducible.
    - sjwright 8y ago
      Then the next question is whether it will work effectively in humans, with no cure-worse-than-the-disease side-effects.
  - wyattpeak 8y ago
    This fad is getting old, pharmacology has little trouble with reproducibility. Few early-stage trials make it to market, but that's an entirely different matter. The treatment they developed, and published in a highly regarded journal, almost certainly works as described. That's a very different beast from a treatment that will be effective in humans to the high standards we hold modern drugs to.
    - garmaine 8y ago
      > The treatment they developed, and published in a highly regarded journal, almost certainly works as described. No, this is simply not true. Unless you also mean “cures the disease, but kills the patient for some other reason” and other net negative outcomes. Most of those studies are on tissue samples, or rodent analogs. That’s not the same as live trials and there is no basis for claiming they’d work in situ.
efiecho 8y ago
Can't help thinking on Winamp. Llama, it really whips the flu's ass.
- psychedictic 8y ago
  Ahh, Justin Frankel's baby. Also, this BBC article is two days old and is now in the 5th position on HN's homepage, for me currently.
  - agumonkey 8y ago
    cough 4 cough
AllegedAlec 8y ago
Reminds me of Roovers' work on nanobodies. Everything old is new again, I guess.
- tomcam 8y ago
  I’m old and am bitterly disappointed that I haven’t been new again
  - brian-armstrong 8y ago
    Try having kids?
    - stochastic_monk 8y ago
      I imagine that that simply reinforces how one is old and not new in contrast with the additional person.
ch0wn 8y ago
I'd love to have more articles that revisit all the amazing sounding findings we read about every day. Especially about the ones that fail trials.
- BurningFrog 8y ago
  Some cynic should really do a web site that just follows up on all miracle cures that flash by the feeds. Let's say take the top viral cure each week, and follow up how it's developing each anniversary. It could actually be really interesting, if done well. But what to call it?
  - jobigoud 8y ago
    I was thinking isitcuredyet.com but the domain is already parked.
arkades 8y ago
This is actually a terribly misleading pop-Sci writeup. Any chance mods can change the link to the actual study? http://science.sciencemag.org/content/362/6414/598 http://science.sciencemag.org/content/362/6414/598
- dang 8y ago
  We try to stick with the best popular article when a technical paper is outside most HN readers' specialty. Is either of these better? http://www.latimes.com/science/sciencenow/la-sci-sn-universal-flu-vaccine-llamas-20181102-story.html http://www.latimes.com/science/sciencenow/la-sci-sn-universa... https://www.sciencemag.org/news/2018/11/nasal-gene-spray-inspired-llama-antibodies-could-prevent-all-types-flu https://www.sciencemag.org/news/2018/11/nasal-gene-spray-ins...
  - arkades 8y ago
    The LA Times article seems like the best of the bunch.
    - headmelted 8y ago
      "Unfortunately, our website is currently unavailable in most European countries." Blocked here in Europe - just FYI in case the link does get changed.
      - neonate 8y ago
        http://archive.is/pdrKz http://archive.is/pdrKz
    - dang 8y ago
      Ok, we've changed to that from https://www.bbc.com/news/health-46078989 https://www.bbc.com/news/health-46078989. Thanks!
      - arkades 8y ago
dirtfree22 8y ago
What I don't get is why are we are spending resources on artificially fortifying our bodies for something that's not event a serious threat? We as society already possess capabilities to survive against threats even more serious. Our body is magnificently apt at defending itself. Disease becomes a problem for us only when we are not taking good care of ourself and our environment, like all the disease outbreaks in UK and US in 1800-1900 when we were living in filthy environment of cities and consuming food/water contaminated by our own filth. Thanks to sanitization revolutions we were able to regain our health. We can once again reach pinnacle of our health if we get rid of newly create pollution in our environment/food.
- koolba 8y ago
  Eh what? Even with modern healthy conditions the flu can be devestating to the very young or old / frail. The vaccination aproach is not just to keep yourself from getting sick, it’s also to prevent yourself from being a vector to infect people who might not be able to be vaccinated or survive if they were to become ill.
  - bdamm 8y ago
    Right, that I think I understand. However, maybe we could do better by eliminating micro-plastics from the food chain and having health guidance that isn’t written by big sugar, big fat, and big agro? Why do we have to inject new manufacturered drugs into the entire population? Where’s the limit with vaccines? Should all viruses and bacteria be eliminated through vaccine? I’ve never seen a drug without a side effect so while I am pro-vax for things like polio and even chickenpox, I really do wonder where the imperative is for flu. We can likely make much greater strides in general numbers by simply providing free access to mental health practitioners. Heck, I bet even returning the US House of Representatives to a 100,000 count per would have meaningful results on the public’s welfare, and that doesn’t require injections!
    - NationOfJoe 8y ago
      i believe the reason you are being down voted here is because we as a society can work on more then one thing at a time. people working on flu vaccines are probably not interested, trained or able to work on public welfare. People who work on public welfare are not interested, trained or able to work on vaccines.
OnlyRepliesToBS 8y ago
llamas are used to pockets
DoctorOetker 8y ago
>It was tested on mice, which were given deadly doses of influenza. I never realized there was an LD50 for influenza viruses (in healthy individuals)...

184 points by broahmed 8y ago

> The genetic instructions for making the antibody were packaged up inside a harmless virus, which was then used to infect the noses of mice. That's interesting. I didn't realize gene therapy could be so localized.

Nasrudith 8y ago
Well every copy of the DNA doesn't make it into the germ-line and viruses generally infect differing types of cells in the first place.
rubatuga 8y ago
Yep, they usually use a pseudo virus that doesn't replicate, called an adeno associated virus. Check out this guys video on his own gene therapy for lactose intolerance : https://m.youtube.com/watch?v=J3FcbFqSoQY https://m.youtube.com/watch?v=J3FcbFqSoQY
rotexo 8y ago
Yep, adeno-associated virus (AAV) vectors seem very promising. Depending on the type of vector used, you can target the eye, joints, liver, lungs, etc. [1]. Relatively recently, the FDA approved the first AAV-based therapy for a rare retinal disorder [2]. Also worth checking out are some promising trials for treatment of severe hemophilia using AAV vectors [3]. These might end up being great, because the current gold standard treatment involves giving people regular injections of recombinant clotting factor protein, which is even more expensive than gene therapy. Plus, with gene therapy, you have one treatment that lasts a long time, versus having to get an infusion of the treatment regularly. [1] (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138125/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138125/) [2] (https://www.labroots.com/trending/drug-discovery/7533/adeno-associated-virus-gene-therapy-fda-approved-rare-retinal-disease https://www.labroots.com/trending/drug-discovery/7533/adeno-...) [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728634/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728634/

BariumBlue 8y ago

I know that cow antibodies are also generally more effective than human antibodies due to their increased length... Why specifically use lamas?

craftyguy 8y ago
The article mentions why.
clort 8y ago
llamas produce very small antibodies that can attack the parts of the virus that are further inside, and these parts do not mutate as often as the outer parts, which our antibodies generally attack. The outer parts mutate pretty quickly, meaning that any vaccine or treatment that we normally provide only works for a short time.
- whatshisface 8y ago
  If the inside parts have more to do with the functioning of the virus (which is what one might guess from hearing that they are more conserved), could targeting them with antibodies bias viral evolution towards colds turning deadly as opposed to slight changes in their shell proteins?
  - WhiteSage 8y ago
    Evolution often makes viruses less deadly, as it wants to maximize dispersion, and killing the host is usually not a good strategy. They will probably just try to mutate to cover those inner parts of the shell proteins.
- arkades 8y ago
  The really terrible pop-sci write-up says because the antibodies are smaller. The actual publication doesn't given a reason for using llamas. The rationale discussed doesn't hold together, either, since nothing in the study is about "small ab penetrating deeper." To quote the actual study: "Moreover, most vaccine-induced antibodies are directed against the highly variable head region of hemagglutinin (HA) and are strain specific. However, broadly neutralizing antibodies (bnAbs) targeting influenza HA have been isolated and characterized (8). Several bnAbs have entered clinical trials as therapeutic agents, but their use in influenza prophylaxis remains elusive because of the incomplete coverage against circulating human influenza A and B viruses, which necessitates administration of a bnAb cocktail, and the need for multiple, high-dose injections for protection throughout the entire influenza season. High serum bnAb levels are required because of poor distribution to the upper airways. We present an alternative strategy for long-lasting protection in which single-domain antibodies (sdAbs) (9) with influenza A or B reactivity are linked together into a multidomain antibody (MDAb) and expressed at the nasopharyngeal mucosa through the intranasal administration of a recombinant adeno-associated virus (AAV) vector (10, 11) encoding the MDAb transgene." Their whole point was to take Ab that target highly-conserved regions and link them together into a, let's call it, multi-tool ab that has a variety of ways of hitting highly conserved regions. Nothing at all about that approach suggests using "smaller ab" to "penetrate deeper." It's true camelids produce single-domain antibodies which are much smaller than the multi-domain antibodies humans use, but that wasn't the goal of the study: on the contrary, using peptide linkers to string together ab sounds like it accomplishes quite the contrary. I think the actual rationale is: "we wanted to string together a bunch of different antibodies to maximize the likelihood of our construction finding a target, and human ab are so big that if we string them together it'll be useless - so we strung together a bunch of small, highly targeted ab, whose final size will still be small enough to allow the multi-headed hydra to interact with viruses."

tw1010 8y ago

I can't bring myself to be in any way happy from reading stuff like this. We get articles like this every freaking day and probably only a fraction of them will ever get into production.

garmaine 8y ago
Only a fraction of them end up being repeatable.
- noja 8y ago
  Those lucky fruit flies and llamas.
- radus 8y ago
  Not my field, but based on what I know of the quality of research in this lab and the fact that it was published in Science, I would be very surprised if the results aren't very solid and reproducible.
  - sjwright 8y ago
    Then the next question is whether it will work effectively in humans, with no cure-worse-than-the-disease side-effects.
- wyattpeak 8y ago
  This fad is getting old, pharmacology has little trouble with reproducibility. Few early-stage trials make it to market, but that's an entirely different matter. The treatment they developed, and published in a highly regarded journal, almost certainly works as described. That's a very different beast from a treatment that will be effective in humans to the high standards we hold modern drugs to.
  - garmaine 8y ago
    > The treatment they developed, and published in a highly regarded journal, almost certainly works as described. No, this is simply not true. Unless you also mean “cures the disease, but kills the patient for some other reason” and other net negative outcomes. Most of those studies are on tissue samples, or rodent analogs. That’s not the same as live trials and there is no basis for claiming they’d work in situ.

efiecho 8y ago

Can't help thinking on Winamp. Llama, it really whips the flu's ass.

psychedictic 8y ago
Ahh, Justin Frankel's baby. Also, this BBC article is two days old and is now in the 5th position on HN's homepage, for me currently.
- agumonkey 8y ago
  cough 4 cough

AllegedAlec 8y ago

Reminds me of Roovers' work on nanobodies. Everything old is new again, I guess.

tomcam 8y ago
I’m old and am bitterly disappointed that I haven’t been new again
- brian-armstrong 8y ago
  Try having kids?
  - stochastic_monk 8y ago
    I imagine that that simply reinforces how one is old and not new in contrast with the additional person.

ch0wn 8y ago

I'd love to have more articles that revisit all the amazing sounding findings we read about every day. Especially about the ones that fail trials.

BurningFrog 8y ago
Some cynic should really do a web site that just follows up on all miracle cures that flash by the feeds. Let's say take the top viral cure each week, and follow up how it's developing each anniversary. It could actually be really interesting, if done well. But what to call it?
- jobigoud 8y ago
  I was thinking isitcuredyet.com but the domain is already parked.

arkades 8y ago

This is actually a terribly misleading pop-Sci writeup. Any chance mods can change the link to the actual study? http://science.sciencemag.org/content/362/6414/598 http://science.sciencemag.org/content/362/6414/598

dang 8y ago
We try to stick with the best popular article when a technical paper is outside most HN readers' specialty. Is either of these better? http://www.latimes.com/science/sciencenow/la-sci-sn-universal-flu-vaccine-llamas-20181102-story.html http://www.latimes.com/science/sciencenow/la-sci-sn-universa... https://www.sciencemag.org/news/2018/11/nasal-gene-spray-inspired-llama-antibodies-could-prevent-all-types-flu https://www.sciencemag.org/news/2018/11/nasal-gene-spray-ins...
- arkades 8y ago
  The LA Times article seems like the best of the bunch.
  - headmelted 8y ago
    "Unfortunately, our website is currently unavailable in most European countries." Blocked here in Europe - just FYI in case the link does get changed.
    - neonate 8y ago
      http://archive.is/pdrKz http://archive.is/pdrKz
  - dang 8y ago
    Ok, we've changed to that from https://www.bbc.com/news/health-46078989 https://www.bbc.com/news/health-46078989. Thanks!
    - arkades 8y ago

dirtfree22 8y ago

What I don't get is why are we are spending resources on artificially fortifying our bodies for something that's not event a serious threat? We as society already possess capabilities to survive against threats even more serious. Our body is magnificently apt at defending itself. Disease becomes a problem for us only when we are not taking good care of ourself and our environment, like all the disease outbreaks in UK and US in 1800-1900 when we were living in filthy environment of cities and consuming food/water contaminated by our own filth. Thanks to sanitization revolutions we were able to regain our health. We can once again reach pinnacle of our health if we get rid of newly create pollution in our environment/food.

koolba 8y ago
Eh what? Even with modern healthy conditions the flu can be devestating to the very young or old / frail. The vaccination aproach is not just to keep yourself from getting sick, it’s also to prevent yourself from being a vector to infect people who might not be able to be vaccinated or survive if they were to become ill.
- bdamm 8y ago
  Right, that I think I understand. However, maybe we could do better by eliminating micro-plastics from the food chain and having health guidance that isn’t written by big sugar, big fat, and big agro? Why do we have to inject new manufacturered drugs into the entire population? Where’s the limit with vaccines? Should all viruses and bacteria be eliminated through vaccine? I’ve never seen a drug without a side effect so while I am pro-vax for things like polio and even chickenpox, I really do wonder where the imperative is for flu. We can likely make much greater strides in general numbers by simply providing free access to mental health practitioners. Heck, I bet even returning the US House of Representatives to a 100,000 count per would have meaningful results on the public’s welfare, and that doesn’t require injections!
  - NationOfJoe 8y ago
    i believe the reason you are being down voted here is because we as a society can work on more then one thing at a time. people working on flu vaccines are probably not interested, trained or able to work on public welfare. People who work on public welfare are not interested, trained or able to work on vaccines.

OnlyRepliesToBS 8y ago

llamas are used to pockets

DoctorOetker 8y ago

>It was tested on mice, which were given deadly doses of influenza. I never realized there was an LD50 for influenza viruses (in healthy individuals)...