11 ms·

NIH Scientists Identify Antibody That Neutralizes Nearly All HIV Strains

595 points by jjuhl 10y ago

ejstronge 10y ago
Not my area of scientific knowledge, but this is a really exciting field! One of the current challenges being worked on is how to train individuals to make these complex antibodies. We've isolated these from people with long-term exposures to HIV, showing that the body can generate these broadly neutralizing antibodies. Some current work is focusing on developing a series of peptides that can coax HIV negative individuals to make these complex antibodies.
- IgorPartola 10y ago
  Are you saying that some HIV positive individuals naturally develop these antibodies over time, curing themselves of HIV? Or am I misreading?
  - dogma1138 10y ago
    Developing antibodies != curing themselves. Your immune system can and does fight the HIV virus, it does loses that fight because HIV attacks the immune system, can hide for years, and has a cell to cell infection vector. The immune system is also limited to what it can do, and when viruses can spread cell to cell there isn't much it can do since there is little to no attack surface available for the immune system to work with in that case. Antibody and therapeutic vaccines can be used as post exposure treatments and combined with other regiments to help slow down or even control the progress of HIV and AIDS in already afflicted patients. A therapeutic vaccine with a regiment of reverse-transcriptase inhibitors and a treatment to control cell suicide upon infection can probably be developed for HIV and for other retroviruses, well excluding the antibodies it is what we already are doing today mostly.
    - rms_returns 10y ago
      >> and has a cell to cell infection vector. I am an absolute noob in science, but still want to ask out of curiosity. If a biological virus can have a cell to cell infection vector, can't an anti-body or immunogen also have a cell-to-cell "replenishing" factor?
      - kendallpark 10y ago
        Antibodies are secreted extracellularly so they won't be any use unless the HIV antigens are expressing on the outside of the cell. There are defense mechanisms for dealing with intracellular viruses but these do not involve antibodies.
      - mac01021 10y ago
        A virus hijacks the resources of a host cell to create copies of itself. These copies can then then move into nearby cells and hijack those too, setting off a biological chain reaction. An antibody is just a protein molecule with no ability to create copies of itself. It might move from one cell to another, but that does create a new synthesizer of the antibody at the new location, and so does not trigger a spread of the antibody throughout the tissue or organism.
      - dogma1138 10y ago
        Like mentioned already by another poster antibodies are an extracellular mechanism, they do not function within the cell. Cell to call transfer and communication happens all the time, cells share nutrients and many other things, some viruses take advantage of that mechanism allowing them to basically cross cellular and tissue boundaries. Some can exploit this to the extreme by actually replicating only parts of themselves in each cell and using the cell to cell transfer highway to be finally assembled in another cell, this is often used to prevent cell suicide since one of the intracellular defense mechanism is basically the cell invoking cell death upon detecting an infection. If you want an analogy from the technology world think about it as staged payloads that some malware use, each payload on it's own is undetectable and even non-functional but when everything reaches the final target all the payloads are assembled into the final piece of malware that takes over the targeted host ;)
  - xenadu02 10y ago
    There are long-term controllers. Some of these people are able to suppress HIV for 10-30 years before eventually developing AIDS. Others have yet to develop AIDS and seem to suppress HIV permanently. That shouldn't be a surprise - some primates species do the same with SIV, basically controlling it permanently. I see the comments about cell-to-cell infection; I don't know what it is about these controllers but it doesn't seem to be a problem for them.
- nonbel 10y ago
  This won't help much since HIV is transferred cell to cell: http://www.news-medical.net/news/20150828/Cell-to-cell-transmission-of-HIV-leads-to-development-of-AIDS.aspx http://www.news-medical.net/news/20150828/Cell-to-cell-trans... Actually, a lot of stuff about HIV makes more sense if you assume the majority (all?) of transmissions occur this way.
  - ejstronge 10y ago
    Interesting, I hadn't heard about that theory of HIV transmission. Do you think that having appropriate IgA secretions in the female genital tract might decrease initial infections?
    - nonbel 10y ago
      1) I think what is understood about the immune system is really, really over-exaggerated. One specific thing is that a lot of studies regarding antibodies may be messed up by the presence of natively unfolded proteins (which will react with any antibody raised towards beta-sheets and give inaccurate mass estimates on western blot). Every anti-body is promiscuous, it just matters how much. 2) Notice I have no quantification or numbers associated with these ideas. As far as I know, no one has ever spent the time to work this out into a real model that can make precise predictions. Accordingly, consider them wild speculations. 3) According to this sketch of an idea, anything that contributes to identifying and lysing non-self cells should reduce transmission in a given tissue.
mrcactu5 10y ago
there's a lot of genetic variation in HIV due to natural selection. in the process of replicating they make many different strains -- mostly very similar to one another. here is an HIV sequence database https://www.hiv.lanl.gov/content/index https://www.hiv.lanl.gov/content/index https://hivdb.stanford.edu/page/who-resistance-list/ https://hivdb.stanford.edu/page/who-resistance-list/ if you take medicine, get off them and try to get back on your medicine, you may find your medicine no longer works. that being said I don't quite know what "neutralize" means in this context, but the NIH seems to feel this result has wide applicability.
jliptzin 10y ago
Not my area of expertise but even if we can address 99% of strains, wouldn't that last 1% just take over and become the new 100% leaving us back where we started? Or is the promise here that we can combine this discovery with another that solves that remaining 1%? Or, do the mutations of that last 1% make HIV less virulent or harder to transmit?
- perlgeek 10y ago
  > Not my area of expertise but even if we can address 99% of strains, wouldn't that last 1% just take over and become the new 100% leaving us back where we started? Not my area of expertise either, but as I understand it, it really depends on how many strains you are infected with. If it's just one, it'd reduce the infections in the next generation of patients by 99%. If the average patient had 10 strains, randomly distributed, it'd still reduce the infection rate by 90% (because there's a 10% chance of having that one resistant strain). Only if all HIV patience had all strains (and I'm pretty sure that's not the case) would it bring us back to where we started.
  - dogma1138 10y ago
    You don't reduce the infection rate by 99% or by 90%, it's not even the correct term really. The transmission rate of HIV is not really dependant on the strain but on the behaviour of the affected host. Since HIV infection can be asymptomatic even for the natural life of a host the transmission rate is then dependant on the environment the social interaction of that host. A host that has unprotected sex (or any other risky activity as far as blood transmitted diseases go) and does not get tested regularly will have a considerably higher transmission rate than a host that has only protected sex and gets tested when they switch partners. Most HIV patients are infected with multiple strains, because at this point most new infections are multi-strain ones due to the lifestyle of the hosts and due to the fact that the virus can mutate in vitro. I'm also not clear how does this press release counts "strains", since it's 16 it's more than just by major types HIV-1 and HIV-2, but then it's the question of what and how they count sub groups. Most people in the west will get infected by HIV-1 Group M type B, type B itself can have several variations, and there are also host specific mutations, and if you are coinfected with another subtype you can have multiple variations of both and also recombinant (a new form made out of several types of the virus due to coinfection of a single cell) variations that may or may not be unique to each host. That said effective post infection and pre AIDS outbreak treatments can drastically reduce of new hosts that end up as transmission vectors and carriers, if HIV becomes a considerably more manageable disease that would allow most infected people to carry on with a normal lifestyle (safely have sex with a partner, and have children) once treated more people are more likely to be tested regularly. If you can also contain the disease to specific subtypes which are regionally locked as sad as it sounds you still doing quite a bit of good since now you can focus your resources on education and containment as well as further research since the transmission rates between say interveinal drug users in Berlin are considerably higher than between a sex worker in nairobi and the same drug users.
koolba 10y ago
Would this type of research lead towards a solution that is preventive (e.g. a vaccine) or something that would treat existing cases?
- atmosx 10y ago
  It's a possibility. Given the lack of details, it's too early to say but the article mentions "prevention" which kinda leads to believe that if this works as we all hope, a cure might be possible.
- akiselev 10y ago
  I'm not an expert in vaccine development but I believe this could lead to a preventative treatment. Unfortunately, the treatment would probably be very dangerous because unlike smallpox or polio, the human body can't effectively fight HIV and an acute infection almost always turns into a chronic one. If a patient's immune system fails to attack a weakened smallpox strain (the vaccine) and it turns into an acute infection, the risk of life altering side effects is minuscule and more often than not, your immune system will fight off the infection. HIV is different because its only real effect on the body is the destruction of T-cells, which the virus uses to reproduce, and there is no stopping that process only slowing it down. If you take an HIV vaccine developed with this antibody and your immune system fails to learn it (or the strain mutates before it has a chance to, which is a remote but very real possibility with retroviruses), you will eventually develop AIDS or spend a lifetime taking expensive drug cocktails with a long list of serious side effects. There are tricks to developing vaccines without using the pathogen directly, like constructing a decoy with the relevant surface proteins, but they're unlikely to work with HIV because it's so simple. When an antibody finds its antigen, it signals the immune system to consume the pathogen and learn about it if it hasn't seen the invader before. Since antibodies share a chemical structure (like DNA and RNA, except more complex), cells in the immune system can memorize the antibody and produce it even if it isn't present in our genetic code. This process is one of the most amazing adaptations in the animal kingdom, allowing complex organisms to compete with the microscopic in the evolutionary arms race, but the immune system needs to see the antibody and pathogen in order create mature B-cells, which adapt to bind to the same pathogen as the antibody. HIV is small, simple, and doesn't have many unique features on the viral package (which contains the RNA) so it'll likely be very hard to produce a decoy for the antibody to latch on to.
wolf550e 10y ago
Can HIV be eradicated completely by all current patients dying (within, say, a century) without transmitting it to anyone else?
- ionforce 10y ago
  Surely there has to be a better way to phrase this.
  - eganist 10y ago
    "Could HIV be eradicated by merely halting all transmission?" Yes.
    - atmosx 10y ago
      Yes, but that would require an effort by an organisation like WHO of a scale never seen before. I would be very proud of the human species if we could pull this off. I think, as a species, we'll master time-travel before consensus...
      - andrepd 10y ago
        Smallpox was a plague of similar proportions, and the world community got together and pulled the massive feat of erradication in a decade.
        atmosx 10y ago
        It's not like HIV.
    - justin66 10y ago
      Given that this virus has already made the species shift four times that we know of, "halting all transmission" is sort of a strange concept.
- jack9 10y ago
  http://www.theaidsinstitute.org/node/259 http://www.theaidsinstitute.org/node/259 You might have to eradicate a number of species.
iaw 10y ago
I feel like the frequency of the "scientific breakthrough" headlines that led to nothing has muted my enthusiasm for remarkable findings like this. There is a huge difference between the NIH announcing a finding and the sensationalist science journalism that is typically inaccurate. I wonder if this divergence erodes the public trust in science.
- nneonneo 10y ago
  An earlier antibody in the same family, VRC01, is in Stage IIb clinical trials for the treatment of HIV. Medical science is slow and extremely methodical, but it can produce practical results. You just have to have patience.
  - ufo 10y ago
    I think the problem is that in popular news you often just get the impression that a "breakthrough" happened but it isn't super clear what the scientist actually did, what are the limitations of their work and what you should expect from future research. So instead of seeing news that say specific things like "this might lead to a monoclonal antiboody treatment in 10 years" or "this could help vaccine research" you end up with a bunch of headlines that sound as if AIDS is going to be cured tomorrow.
    - iaw 10y ago
      Thanks ufo, that's the point I was trying to make.
- codecamper 10y ago
  grumpy
nneonneo 10y ago
I read through the original paper (https://dx.doi.org/10.1016/j.immuni.2016.10.027 https://dx.doi.org/10.1016/j.immuni.2016.10.027, paywalled). In essence, an antibody called N6 was extracted from an HIV patient. The patient is a long-term nonprogressor who has had HIV for 21 years, but an exceptionally low viral load of <1000/mL and normal CD4 T-cell count. This indicates that his immune system has kept the virus at bay for all these years with essentially no ill effect. HIV viruses have a surface protein complex called Env, which binds to the CD4 surface protein to gain entry to T-cells (part of the immune system). HIV cannot transmit without this protein complex, and so certain parts of the complex are very well conserved across different HIV strains. N6 binds to this part of Env, in some sense "simulating" CD4. However, because it's just an antibody and not a cell, once Env is bound it cannot infect anything. This is what makes N6 a neutralizing antibody. The thing that makes N6 special (more potent and more broadly applicable) is that it is able to avoid the parts of Env that HIV doesn't need for replication. Imagine Env as a wrench. The head of the wrench is a specific hex shape to mate with CD4 and can't change. Antibodies can grab on to the wrench handle to prevent infection. But the handle can change, and HIV regularly mutates this part to avoid being caught - adding side branches, changing the shape, and so forth. N6 is cleverly arranged so that it can strongly bind to the wrench without grabbing the handle too strongly - in other words, it tightly binds the head of the wrench like a person wrapping a thumb and index finger around it (this hand analogy appears in the paper). The result is that HIV has a much harder time getting out from under the antibody, since mutating itself to alter the head shape would also affect infectivity. Now that larger HIV screening trials are done, and the technology has advanced to better detect such super-antibodies, more of these clever antibodies may be discovered. We may yet have a good shot at defeating this tricky virus!
- errantspark 10y ago
  Reminds me of Shapely from William Gibson's Bridge Trilogy "He was discovered by the AIDS industry when he had already been HIV-positive for twelve years. His strain of HIV was notpathogenic but was able to kill the lethal strain of HIV. By isolating his mutant strain of HIV it was possible to develop an AIDS vaccine."
  - 10y ago
belorn 10y ago
Is this NIH scientist funded by tax money, and if so, what does that mean for a future vaccine or drug? Will it still be patented, and if so, who will hold the patent?
- nneonneo 10y ago
  There are 35 authors, some of whom are funded by the NIH. Here's the full funding acknowledgment statement: Support for this work was provided by the Intramural Research Program and the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH. Use of sector 22 (Southeast Region Collaborative Access team) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science under contract number W-31-109-Eng-38.
- refurb 10y ago
  Look up the Bayh-Dole act. The researcher who receives the NIH funding is free to patent it and sell that patent to a drug company.
  - mattkrause 10y ago
    Are you sure about that? Bayh-Dole covers inventions arising from extramural funding (i.e., the NIH provides a grant to people who are employed elsewhere). I'm not sure how it applies here, where ~80% of the authors appear to be directly employed by some of the NIH's Institutes.
    - refurb 10y ago
      Oops! Didn't catch that. If they work for the NIH, then the patent would be the NIH's.
c3534l 10y ago
I've been hearing about "this looks like a cure for AIDS!" at least once a year since the 90s. It always just needs to go through FDA testing and approval and then evaporates. What we've gotten instead is incremental improvements in the treatment of the disease. Maybe if you tell me there is a new treatment that completely cures some 1% of those treated I'll buy it. But this, this is preliminary research.
peter303 10y ago
Since the discovery of the virus 32 years ago there have been a large number of treatments successful in animals or the test tube, only to fail in humans
hackuser 10y ago
If you feel these discoveries are important and you are an American, let your Congresspeople know that you support NIH funding.
grogenaut 10y ago
So in a case like this does the patient own any patentability of their own antibodies? Or did they sign it away in treatment/study?
- Hondor 10y ago
  Patents are to incentivise inventions. If an HIV patient could patent their antibodies, that would limit their usefulness while also giving no incentive to anyone to invent better ones, since you can't invent them - just wait and hope if they appear. So I certainly hope they can't do that. Rather, it's the researchers who went looking for them who should be granted any patent rights. They're the ones who could work harder to produce better results and can have their performance improved with more rewards like a patent's monopoly.
throw16 10y ago
the patient has to take it the rest of their life ...the perfect money maker

595 points by jjuhl 10y ago

Not my area of scientific knowledge, but this is a really exciting field! One of the current challenges being worked on is how to train individuals to make these complex antibodies. We've isolated these from people with long-term exposures to HIV, showing that the body can generate these broadly neutralizing antibodies. Some current work is focusing on developing a series of peptides that can coax HIV negative individuals to make these complex antibodies.

IgorPartola 10y ago
Are you saying that some HIV positive individuals naturally develop these antibodies over time, curing themselves of HIV? Or am I misreading?
- dogma1138 10y ago
  Developing antibodies != curing themselves. Your immune system can and does fight the HIV virus, it does loses that fight because HIV attacks the immune system, can hide for years, and has a cell to cell infection vector. The immune system is also limited to what it can do, and when viruses can spread cell to cell there isn't much it can do since there is little to no attack surface available for the immune system to work with in that case. Antibody and therapeutic vaccines can be used as post exposure treatments and combined with other regiments to help slow down or even control the progress of HIV and AIDS in already afflicted patients. A therapeutic vaccine with a regiment of reverse-transcriptase inhibitors and a treatment to control cell suicide upon infection can probably be developed for HIV and for other retroviruses, well excluding the antibodies it is what we already are doing today mostly.
  - rms_returns 10y ago
    >> and has a cell to cell infection vector. I am an absolute noob in science, but still want to ask out of curiosity. If a biological virus can have a cell to cell infection vector, can't an anti-body or immunogen also have a cell-to-cell "replenishing" factor?
    - kendallpark 10y ago
      Antibodies are secreted extracellularly so they won't be any use unless the HIV antigens are expressing on the outside of the cell. There are defense mechanisms for dealing with intracellular viruses but these do not involve antibodies.
    - mac01021 10y ago
      A virus hijacks the resources of a host cell to create copies of itself. These copies can then then move into nearby cells and hijack those too, setting off a biological chain reaction. An antibody is just a protein molecule with no ability to create copies of itself. It might move from one cell to another, but that does create a new synthesizer of the antibody at the new location, and so does not trigger a spread of the antibody throughout the tissue or organism.
    - dogma1138 10y ago
      Like mentioned already by another poster antibodies are an extracellular mechanism, they do not function within the cell. Cell to call transfer and communication happens all the time, cells share nutrients and many other things, some viruses take advantage of that mechanism allowing them to basically cross cellular and tissue boundaries. Some can exploit this to the extreme by actually replicating only parts of themselves in each cell and using the cell to cell transfer highway to be finally assembled in another cell, this is often used to prevent cell suicide since one of the intracellular defense mechanism is basically the cell invoking cell death upon detecting an infection. If you want an analogy from the technology world think about it as staged payloads that some malware use, each payload on it's own is undetectable and even non-functional but when everything reaches the final target all the payloads are assembled into the final piece of malware that takes over the targeted host ;)
- xenadu02 10y ago
  There are long-term controllers. Some of these people are able to suppress HIV for 10-30 years before eventually developing AIDS. Others have yet to develop AIDS and seem to suppress HIV permanently. That shouldn't be a surprise - some primates species do the same with SIV, basically controlling it permanently. I see the comments about cell-to-cell infection; I don't know what it is about these controllers but it doesn't seem to be a problem for them.
nonbel 10y ago
This won't help much since HIV is transferred cell to cell: http://www.news-medical.net/news/20150828/Cell-to-cell-transmission-of-HIV-leads-to-development-of-AIDS.aspx http://www.news-medical.net/news/20150828/Cell-to-cell-trans... Actually, a lot of stuff about HIV makes more sense if you assume the majority (all?) of transmissions occur this way.
- ejstronge 10y ago
  Interesting, I hadn't heard about that theory of HIV transmission. Do you think that having appropriate IgA secretions in the female genital tract might decrease initial infections?
  - nonbel 10y ago
    1) I think what is understood about the immune system is really, really over-exaggerated. One specific thing is that a lot of studies regarding antibodies may be messed up by the presence of natively unfolded proteins (which will react with any antibody raised towards beta-sheets and give inaccurate mass estimates on western blot). Every anti-body is promiscuous, it just matters how much. 2) Notice I have no quantification or numbers associated with these ideas. As far as I know, no one has ever spent the time to work this out into a real model that can make precise predictions. Accordingly, consider them wild speculations. 3) According to this sketch of an idea, anything that contributes to identifying and lysing non-self cells should reduce transmission in a given tissue.

mrcactu5 10y ago

there's a lot of genetic variation in HIV due to natural selection. in the process of replicating they make many different strains -- mostly very similar to one another. here is an HIV sequence database https://www.hiv.lanl.gov/content/index https://www.hiv.lanl.gov/content/index https://hivdb.stanford.edu/page/who-resistance-list/ https://hivdb.stanford.edu/page/who-resistance-list/ if you take medicine, get off them and try to get back on your medicine, you may find your medicine no longer works. that being said I don't quite know what "neutralize" means in this context, but the NIH seems to feel this result has wide applicability.

jliptzin 10y ago

Not my area of expertise but even if we can address 99% of strains, wouldn't that last 1% just take over and become the new 100% leaving us back where we started? Or is the promise here that we can combine this discovery with another that solves that remaining 1%? Or, do the mutations of that last 1% make HIV less virulent or harder to transmit?

perlgeek 10y ago
> Not my area of expertise but even if we can address 99% of strains, wouldn't that last 1% just take over and become the new 100% leaving us back where we started? Not my area of expertise either, but as I understand it, it really depends on how many strains you are infected with. If it's just one, it'd reduce the infections in the next generation of patients by 99%. If the average patient had 10 strains, randomly distributed, it'd still reduce the infection rate by 90% (because there's a 10% chance of having that one resistant strain). Only if all HIV patience had all strains (and I'm pretty sure that's not the case) would it bring us back to where we started.
- dogma1138 10y ago
  You don't reduce the infection rate by 99% or by 90%, it's not even the correct term really. The transmission rate of HIV is not really dependant on the strain but on the behaviour of the affected host. Since HIV infection can be asymptomatic even for the natural life of a host the transmission rate is then dependant on the environment the social interaction of that host. A host that has unprotected sex (or any other risky activity as far as blood transmitted diseases go) and does not get tested regularly will have a considerably higher transmission rate than a host that has only protected sex and gets tested when they switch partners. Most HIV patients are infected with multiple strains, because at this point most new infections are multi-strain ones due to the lifestyle of the hosts and due to the fact that the virus can mutate in vitro. I'm also not clear how does this press release counts "strains", since it's 16 it's more than just by major types HIV-1 and HIV-2, but then it's the question of what and how they count sub groups. Most people in the west will get infected by HIV-1 Group M type B, type B itself can have several variations, and there are also host specific mutations, and if you are coinfected with another subtype you can have multiple variations of both and also recombinant (a new form made out of several types of the virus due to coinfection of a single cell) variations that may or may not be unique to each host. That said effective post infection and pre AIDS outbreak treatments can drastically reduce of new hosts that end up as transmission vectors and carriers, if HIV becomes a considerably more manageable disease that would allow most infected people to carry on with a normal lifestyle (safely have sex with a partner, and have children) once treated more people are more likely to be tested regularly. If you can also contain the disease to specific subtypes which are regionally locked as sad as it sounds you still doing quite a bit of good since now you can focus your resources on education and containment as well as further research since the transmission rates between say interveinal drug users in Berlin are considerably higher than between a sex worker in nairobi and the same drug users.

koolba 10y ago

Would this type of research lead towards a solution that is preventive (e.g. a vaccine) or something that would treat existing cases?

atmosx 10y ago
It's a possibility. Given the lack of details, it's too early to say but the article mentions "prevention" which kinda leads to believe that if this works as we all hope, a cure might be possible.
akiselev 10y ago
I'm not an expert in vaccine development but I believe this could lead to a preventative treatment. Unfortunately, the treatment would probably be very dangerous because unlike smallpox or polio, the human body can't effectively fight HIV and an acute infection almost always turns into a chronic one. If a patient's immune system fails to attack a weakened smallpox strain (the vaccine) and it turns into an acute infection, the risk of life altering side effects is minuscule and more often than not, your immune system will fight off the infection. HIV is different because its only real effect on the body is the destruction of T-cells, which the virus uses to reproduce, and there is no stopping that process only slowing it down. If you take an HIV vaccine developed with this antibody and your immune system fails to learn it (or the strain mutates before it has a chance to, which is a remote but very real possibility with retroviruses), you will eventually develop AIDS or spend a lifetime taking expensive drug cocktails with a long list of serious side effects. There are tricks to developing vaccines without using the pathogen directly, like constructing a decoy with the relevant surface proteins, but they're unlikely to work with HIV because it's so simple. When an antibody finds its antigen, it signals the immune system to consume the pathogen and learn about it if it hasn't seen the invader before. Since antibodies share a chemical structure (like DNA and RNA, except more complex), cells in the immune system can memorize the antibody and produce it even if it isn't present in our genetic code. This process is one of the most amazing adaptations in the animal kingdom, allowing complex organisms to compete with the microscopic in the evolutionary arms race, but the immune system needs to see the antibody and pathogen in order create mature B-cells, which adapt to bind to the same pathogen as the antibody. HIV is small, simple, and doesn't have many unique features on the viral package (which contains the RNA) so it'll likely be very hard to produce a decoy for the antibody to latch on to.

wolf550e 10y ago

Can HIV be eradicated completely by all current patients dying (within, say, a century) without transmitting it to anyone else?

ionforce 10y ago
Surely there has to be a better way to phrase this.
- eganist 10y ago
  "Could HIV be eradicated by merely halting all transmission?" Yes.
  - atmosx 10y ago
    Yes, but that would require an effort by an organisation like WHO of a scale never seen before. I would be very proud of the human species if we could pull this off. I think, as a species, we'll master time-travel before consensus...
    - andrepd 10y ago
      Smallpox was a plague of similar proportions, and the world community got together and pulled the massive feat of erradication in a decade.
      - atmosx 10y ago
        It's not like HIV.
  - justin66 10y ago
    Given that this virus has already made the species shift four times that we know of, "halting all transmission" is sort of a strange concept.
jack9 10y ago
http://www.theaidsinstitute.org/node/259 http://www.theaidsinstitute.org/node/259 You might have to eradicate a number of species.

iaw 10y ago

I feel like the frequency of the "scientific breakthrough" headlines that led to nothing has muted my enthusiasm for remarkable findings like this. There is a huge difference between the NIH announcing a finding and the sensationalist science journalism that is typically inaccurate. I wonder if this divergence erodes the public trust in science.

nneonneo 10y ago
An earlier antibody in the same family, VRC01, is in Stage IIb clinical trials for the treatment of HIV. Medical science is slow and extremely methodical, but it can produce practical results. You just have to have patience.
- ufo 10y ago
  I think the problem is that in popular news you often just get the impression that a "breakthrough" happened but it isn't super clear what the scientist actually did, what are the limitations of their work and what you should expect from future research. So instead of seeing news that say specific things like "this might lead to a monoclonal antiboody treatment in 10 years" or "this could help vaccine research" you end up with a bunch of headlines that sound as if AIDS is going to be cured tomorrow.
  - iaw 10y ago
    Thanks ufo, that's the point I was trying to make.
codecamper 10y ago
grumpy

nneonneo 10y ago

I read through the original paper (https://dx.doi.org/10.1016/j.immuni.2016.10.027 https://dx.doi.org/10.1016/j.immuni.2016.10.027, paywalled). In essence, an antibody called N6 was extracted from an HIV patient. The patient is a long-term nonprogressor who has had HIV for 21 years, but an exceptionally low viral load of <1000/mL and normal CD4 T-cell count. This indicates that his immune system has kept the virus at bay for all these years with essentially no ill effect. HIV viruses have a surface protein complex called Env, which binds to the CD4 surface protein to gain entry to T-cells (part of the immune system). HIV cannot transmit without this protein complex, and so certain parts of the complex are very well conserved across different HIV strains. N6 binds to this part of Env, in some sense "simulating" CD4. However, because it's just an antibody and not a cell, once Env is bound it cannot infect anything. This is what makes N6 a neutralizing antibody. The thing that makes N6 special (more potent and more broadly applicable) is that it is able to avoid the parts of Env that HIV doesn't need for replication. Imagine Env as a wrench. The head of the wrench is a specific hex shape to mate with CD4 and can't change. Antibodies can grab on to the wrench handle to prevent infection. But the handle can change, and HIV regularly mutates this part to avoid being caught - adding side branches, changing the shape, and so forth. N6 is cleverly arranged so that it can strongly bind to the wrench without grabbing the handle too strongly - in other words, it tightly binds the head of the wrench like a person wrapping a thumb and index finger around it (this hand analogy appears in the paper). The result is that HIV has a much harder time getting out from under the antibody, since mutating itself to alter the head shape would also affect infectivity. Now that larger HIV screening trials are done, and the technology has advanced to better detect such super-antibodies, more of these clever antibodies may be discovered. We may yet have a good shot at defeating this tricky virus!

errantspark 10y ago
Reminds me of Shapely from William Gibson's Bridge Trilogy "He was discovered by the AIDS industry when he had already been HIV-positive for twelve years. His strain of HIV was notpathogenic but was able to kill the lethal strain of HIV. By isolating his mutant strain of HIV it was possible to develop an AIDS vaccine."
- 10y ago

belorn 10y ago

Is this NIH scientist funded by tax money, and if so, what does that mean for a future vaccine or drug? Will it still be patented, and if so, who will hold the patent?

nneonneo 10y ago
There are 35 authors, some of whom are funded by the NIH. Here's the full funding acknowledgment statement: Support for this work was provided by the Intramural Research Program and the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH. Use of sector 22 (Southeast Region Collaborative Access team) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science under contract number W-31-109-Eng-38.
refurb 10y ago
Look up the Bayh-Dole act. The researcher who receives the NIH funding is free to patent it and sell that patent to a drug company.
- mattkrause 10y ago
  Are you sure about that? Bayh-Dole covers inventions arising from extramural funding (i.e., the NIH provides a grant to people who are employed elsewhere). I'm not sure how it applies here, where ~80% of the authors appear to be directly employed by some of the NIH's Institutes.
  - refurb 10y ago
    Oops! Didn't catch that. If they work for the NIH, then the patent would be the NIH's.

c3534l 10y ago

I've been hearing about "this looks like a cure for AIDS!" at least once a year since the 90s. It always just needs to go through FDA testing and approval and then evaporates. What we've gotten instead is incremental improvements in the treatment of the disease. Maybe if you tell me there is a new treatment that completely cures some 1% of those treated I'll buy it. But this, this is preliminary research.

peter303 10y ago

Since the discovery of the virus 32 years ago there have been a large number of treatments successful in animals or the test tube, only to fail in humans

hackuser 10y ago

If you feel these discoveries are important and you are an American, let your Congresspeople know that you support NIH funding.

grogenaut 10y ago

So in a case like this does the patient own any patentability of their own antibodies? Or did they sign it away in treatment/study?

Hondor 10y ago
Patents are to incentivise inventions. If an HIV patient could patent their antibodies, that would limit their usefulness while also giving no incentive to anyone to invent better ones, since you can't invent them - just wait and hope if they appear. So I certainly hope they can't do that. Rather, it's the researchers who went looking for them who should be granted any patent rights. They're the ones who could work harder to produce better results and can have their performance improved with more rewards like a patent's monopoly.

throw16 10y ago

the patient has to take it the rest of their life ...the perfect money maker