12 ms·

Immunity Project – HIV Vaccine Development Program [pdf]

40 points by humanfromearth 13y ago

icinnamon 13y ago
Ian from the Immunity Project (YC W14) team here! Happy to answer any questions you may have.
- vertis 13y ago
  Excuse my lack of knowledge in this area, but is this vaccine purely preventative, or is it possible to administer it to someone already infected. I know/believe with traditional vaccines that you usually have to do it before infection. (Though could be wrong in this regard as well) If not, why not?
  - rposborne 13y ago
    The definition of a vaccine is that it is preventative vs. a cure which is removing a disease from a previously infected patient. "A vaccine is a biological preparation that improves immunity to a particular disease."
    - vertis 13y ago
      Yes, but immunity has many definitions, including 'to fight off'. Since it's essentially teaching the immune system, why does this not work when the patient is already infected. I thought there may be some difference between this and traditional vaccines as well.
      - j2d3 13y ago
        This story discusses other HIV vaccine efforts that are targeted at already infected and stop the dependence on the HIV meds: http://www.livescience.com/18107-hiv-therapeutic-vaccines-promise.html http://www.livescience.com/18107-hiv-therapeutic-vaccines-pr... according to that article there are 34 million people already infected worldwide.
  - howiediamond 13y ago
    Howie from the Immunity Project here. Thanks for your question! We're really just focusing on the preventive aspect of this vaccine as we head into our Phase I human clinical trials.
    - j2d3 13y ago
      Hi Howie, can you elaborate? You didn't really address the why / why not aspect of the question. Since the Immunity Project concept relies on training the immune system to mount a successful response against HIV, why would it not present some benefit to an already-infected person whose infection is otherwise controlled with drugs? You may just be focusing on the preventative aspect, but there are many millions worldwide who are concerned with controlling HIV without depending on expensive antiviral drugs that in many cases are completely unavailable.
      - 1457389 13y ago
        I'll try and address this since no one has answered yet. One of the reasons it would be very hard to justify testing this first as a cure is because AIDS patients are by definition immunodeficient. Their Helper T cells (the CD4s mentioned) are being rapidly co-opted by the virus and subject to destruction. In such an environment it is difficult to mount an immune response because the Helper T cells are so instrumental to enabling the cytotoxic immune responses instigated by this study (the CD8 cells are your cytotoxic "killer" T cells). Any trial run on humans already suffering from AIDS would be muddied by this effect, where the already compromised immune system cannot mount a robust response even were it able to develop CD8 killer cells specific to the HIV epitope they vaccinate with. Phase I trials are high risk, and especially for a bootstrapped team like this, have a lot riding on them. An early failure can doom a technology in this industry, so it is important to focus on testing in an environment where you have the best shot at success. Downstream studies can focus on other applications if needed.
        j2d3 13y ago
        There are many millions of people who have HIV but not AIDS. Their immune systems work well, and their viral levels are controlled by medications. These people are on US health insurance and are highly monitored already, and easy to enroll in studies, easily accessed and monitored - as they already conform to an HIV medication regimen and see their doctors regularly. Why would a company not test a technology that may well benefit both infected and uninfected people on both populations? You would only have more data. It will take much longer to see the results if you are only studying it as a preventative measure because you have to wait (a really long time, I would suspect) to see which of your study ends up getting HIV. Additionally, you'd need to study those that do get HIV (if some do, and some probably would, as even the best vaccines aren't 100% effective) and try to see if you can tell if their infection progresses differently or if it is somehow augmented by the vaccination's boost to the immune system. I mean... your explanation doesn't actually make that much sense to me. Why not test both populations?
rgejman 13y ago
Some thoughts on this white paper, with the caveat that I'm not sure how much of what is discussed they have done and how much of it is what they are planning to do. The white paper is light on details and I re-iterate my appeal for them to release their data (at least in summary form). My apologies for some of the technical language--I want to write this first and then I can clarify the hard stuff (or you can google it) This vaccine relies on inducing immunity to an HIV peptide* (i.e. a ~9 amino acid cleavage product of an HIV protein) that is predicted to bind to HLA molecules. At first blush, this sounds like a great idea--let's immunize people to the very thing that the immune system is supposed to recognize as bad! Unfortunately, this has been tried lots of times and usually doesn't work very well, if at all. It's been tried in cancer, it's been tried in HIV, it's been tried in practically any system you can imagine. I'm not saying that peptide vaccines don't ever work (hell, my lab has worked on one)--I'm just saying that they have had lots of promise and limited successes. In fact, animals and patients have been immunized to many cleavage products of many cancer associated antigens to little, if any, effect—or effects in animals but not in humans. We can hem and haw all day about what the specific studies show, but suffice it to say that peptide vaccines are an old idea. Perhaps Immunity will get lucky here, but I'd be surprised if there isn't a lab somewhere that has tried immunizing animals to every single breakdown product of HIV proteins already. Immunity's white paper says that their putatively immunogenic human peptide cannot be tested in animal models because it will only bind to human HLA. So they are planning to use a mouse-analog of the human peptide to do their animal testing (or have already done this?). That is, they are planning to use (or maybe have already used?) a completely different peptide (probably 1-3 amino acids different from the human version) in animal studies than what they would use in patients. This may be a significant difference... or it might not be. There's no way to tell a priori. A more classical and IMO better approach would be to identify T cell receptor clones from patients with HIV (or without HIV) that bind to these peptides (using tetramer staining, phage display or some other high-throughput technology), demonstrate that humans are capable of creating T cells that recognize their putatively immunogenic peptide followed by T cell killing assays on cells presenting their peptide of interest. There are other approaches, but that is a commonly used one in the field. * in some places the white paper says "peptides" and in other it says "peptide" so it's not clear if we are talking about 1 peptide or multiple. I think they are mostly talking about multiple peptides, because they want to immunize people no matter their HLA type. Different HLA types bind to different peptides. So if you have HLA A02 you will bind different peptides than if you have HLA A24... and so on for all the different HLA types.
midas007 13y ago
Interesting. Would Gates and a couple others be willing to cut a few large checks to just make it happen? This is something that should be fast-tracked. As in right now, please.
- icinnamon 13y ago
  Ian from Immunity Project here. We've actually chatted with a few of these large foundations and they are very interested. They want to see some Phase I data first, so that's why we went ahead with the crowdfunding campaign to help us get to that point! Check it out: http://pledge.immunityproject.org http://pledge.immunityproject.org
  - rposborne 13y ago
    Have any of them giving you all benchmarks to hit to secure funding?
lvryc 13y ago
They're also running a kickstarter-style crowdfunding attempt at https://pledge.immunityproject.org/the-free-hiv-aids-vaccine https://pledge.immunityproject.org/the-free-hiv-aids-vaccine .
- icinnamon 13y ago
  We are indeed!
rgejman 13y ago
Another thing I want to point out is that your home page touts safety as a design point. The text under "SAFE" says "Our vaccine does not contain killed viruses, live viruses, or genetically-modified viruses." I STRONGLY object to this language as it implies that inactivated (killed) and live* viruses are unsafe in general. This is simply not true. I believe most clinically used vaccines are either inactivated or attenuated. I understand that you're trying to make sure people understand that your vaccine is safe. However, implying that other vaccines are unsafe because they are inactivated or attenuated does a disservice to the entire vaccine industry. *I think you mean 'attenuated' here, not live
- reidrubsamen 13y ago
  Thanks for the comment! We did not mean to imply that existing vaccines were dangerous and will modify the language on the site to clarify.
kayhi 13y ago
Is there more basic research supporting this interaction (crystallographic or otherwise) between the peptide and T cell? The paper feels like to jumps right into animal models. "specific points identified by a data-driven analysis of actual individuals’ immune systems" pg1 What is the data in this case? What is the sequence of the peptide(s) that are incorporated into the PLGA? Side note: our start up works on helping biotech companies source reagents, supplies and equipment, we should be able to save you about ~15% on the ~475k part of the budget
- naveenspark 13y ago
  Naveen here from Immunity Project. Thanks for the question. We have not done receptor analysis. We are using animal models as our starting point - we are looking for an immune response with memory to the administered peptides - if we get that response in Phase I we should be in good shape! We received the peptides from researchers who have a manuscript in publication and would like us to keep the sequences confidential until they publish. Please see below for similar statistical research looking for targets to beneficial regions on HIV: Mothe B, Anuska L, Ibarrondo J, Daniels M, Miranda C, Zamarreno J, et al. Definition of the viral targets of protective HIV-1-specific T cell responses. Journal of Translational Medicine 2011;9(208):20. re: your startup / cost savings on reagents, supplies and equipment, we would love to talk to you about that. Please email us at team@immunityproject.org. Thanks!
ciokan 13y ago
I would be very curious to know if the team received any kind of pressure to stop what they're doing or if they will communicate if such thing would happen. Don't want to sound cynical, I just watched a lot on the subject recently and it seems there's a huge industry behind having a lot more benefits (material ones) from the actual sick people and their life-long expensive treatments compared to a vaccine. Even if it doesn't work God bless to you all for trying this. It's a wonderful thing to get you up in the morning.
- naveenspark 13y ago
  Thank you for the kind words and support! We are very focused on our stated goal which is ending HIV/AIDS with a free vaccine. We haven't received any pressure to stop our work yet. If we do we will definitely let you know so we can get your help in fighting back!
- limpon 13y ago
  I've heard lots of people speculating that the big pharma companies would be better of if there would always be HIV and they can sell their ART pills for live. But on the other hand if one of them is the first one to create a HIV immunization, this alone will make them so extremely rich. An effective HIV immunization will become standard immunization for all people in the western world and the WHO and UN will take all in their power to immunize as many people worldwide as possible. Just imagine the amount of doses that will have to be produced. And you would be the only one company having this product. This has way more financial gain that being one of the dozens of companies that produce ART therapies. On top of that a few people working in high positions of big pharma companies are still "nice" people who would actually be proud of curing a disease. Not everyone just counts their dollars every day and hopes that more people get sick.
  - ciokan 13y ago
    yes but op website says they will release it for free, thats why i'm asking in the first place.

Ian from the Immunity Project (YC W14) team here! Happy to answer any questions you may have.

vertis 13y ago
Excuse my lack of knowledge in this area, but is this vaccine purely preventative, or is it possible to administer it to someone already infected. I know/believe with traditional vaccines that you usually have to do it before infection. (Though could be wrong in this regard as well) If not, why not?
- rposborne 13y ago
  The definition of a vaccine is that it is preventative vs. a cure which is removing a disease from a previously infected patient. "A vaccine is a biological preparation that improves immunity to a particular disease."
  - vertis 13y ago
    Yes, but immunity has many definitions, including 'to fight off'. Since it's essentially teaching the immune system, why does this not work when the patient is already infected. I thought there may be some difference between this and traditional vaccines as well.
    - j2d3 13y ago
      This story discusses other HIV vaccine efforts that are targeted at already infected and stop the dependence on the HIV meds: http://www.livescience.com/18107-hiv-therapeutic-vaccines-promise.html http://www.livescience.com/18107-hiv-therapeutic-vaccines-pr... according to that article there are 34 million people already infected worldwide.
- howiediamond 13y ago
  Howie from the Immunity Project here. Thanks for your question! We're really just focusing on the preventive aspect of this vaccine as we head into our Phase I human clinical trials.
  - j2d3 13y ago
    Hi Howie, can you elaborate? You didn't really address the why / why not aspect of the question. Since the Immunity Project concept relies on training the immune system to mount a successful response against HIV, why would it not present some benefit to an already-infected person whose infection is otherwise controlled with drugs? You may just be focusing on the preventative aspect, but there are many millions worldwide who are concerned with controlling HIV without depending on expensive antiviral drugs that in many cases are completely unavailable.
    - 1457389 13y ago
      I'll try and address this since no one has answered yet. One of the reasons it would be very hard to justify testing this first as a cure is because AIDS patients are by definition immunodeficient. Their Helper T cells (the CD4s mentioned) are being rapidly co-opted by the virus and subject to destruction. In such an environment it is difficult to mount an immune response because the Helper T cells are so instrumental to enabling the cytotoxic immune responses instigated by this study (the CD8 cells are your cytotoxic "killer" T cells). Any trial run on humans already suffering from AIDS would be muddied by this effect, where the already compromised immune system cannot mount a robust response even were it able to develop CD8 killer cells specific to the HIV epitope they vaccinate with. Phase I trials are high risk, and especially for a bootstrapped team like this, have a lot riding on them. An early failure can doom a technology in this industry, so it is important to focus on testing in an environment where you have the best shot at success. Downstream studies can focus on other applications if needed.
      - j2d3 13y ago
        There are many millions of people who have HIV but not AIDS. Their immune systems work well, and their viral levels are controlled by medications. These people are on US health insurance and are highly monitored already, and easy to enroll in studies, easily accessed and monitored - as they already conform to an HIV medication regimen and see their doctors regularly. Why would a company not test a technology that may well benefit both infected and uninfected people on both populations? You would only have more data. It will take much longer to see the results if you are only studying it as a preventative measure because you have to wait (a really long time, I would suspect) to see which of your study ends up getting HIV. Additionally, you'd need to study those that do get HIV (if some do, and some probably would, as even the best vaccines aren't 100% effective) and try to see if you can tell if their infection progresses differently or if it is somehow augmented by the vaccination's boost to the immune system. I mean... your explanation doesn't actually make that much sense to me. Why not test both populations?

Some thoughts on this white paper, with the caveat that I'm not sure how much of what is discussed they have done and how much of it is what they are planning to do. The white paper is light on details and I re-iterate my appeal for them to release their data (at least in summary form). My apologies for some of the technical language--I want to write this first and then I can clarify the hard stuff (or you can google it) This vaccine relies on inducing immunity to an HIV peptide* (i.e. a ~9 amino acid cleavage product of an HIV protein) that is predicted to bind to HLA molecules. At first blush, this sounds like a great idea--let's immunize people to the very thing that the immune system is supposed to recognize as bad! Unfortunately, this has been tried lots of times and usually doesn't work very well, if at all. It's been tried in cancer, it's been tried in HIV, it's been tried in practically any system you can imagine. I'm not saying that peptide vaccines don't ever work (hell, my lab has worked on one)--I'm just saying that they have had lots of promise and limited successes. In fact, animals and patients have been immunized to many cleavage products of many cancer associated antigens to little, if any, effect—or effects in animals but not in humans. We can hem and haw all day about what the specific studies show, but suffice it to say that peptide vaccines are an old idea. Perhaps Immunity will get lucky here, but I'd be surprised if there isn't a lab somewhere that has tried immunizing animals to every single breakdown product of HIV proteins already. Immunity's white paper says that their putatively immunogenic human peptide cannot be tested in animal models because it will only bind to human HLA. So they are planning to use a mouse-analog of the human peptide to do their animal testing (or have already done this?). That is, they are planning to use (or maybe have already used?) a completely different peptide (probably 1-3 amino acids different from the human version) in animal studies than what they would use in patients. This may be a significant difference... or it might not be. There's no way to tell a priori. A more classical and IMO better approach would be to identify T cell receptor clones from patients with HIV (or without HIV) that bind to these peptides (using tetramer staining, phage display or some other high-throughput technology), demonstrate that humans are capable of creating T cells that recognize their putatively immunogenic peptide followed by T cell killing assays on cells presenting their peptide of interest. There are other approaches, but that is a commonly used one in the field. * in some places the white paper says "peptides" and in other it says "peptide" so it's not clear if we are talking about 1 peptide or multiple. I think they are mostly talking about multiple peptides, because they want to immunize people no matter their HLA type. Different HLA types bind to different peptides. So if you have HLA A02 you will bind different peptides than if you have HLA A24... and so on for all the different HLA types.

midas007 13y ago

Interesting. Would Gates and a couple others be willing to cut a few large checks to just make it happen? This is something that should be fast-tracked. As in right now, please.

icinnamon 13y ago
Ian from Immunity Project here. We've actually chatted with a few of these large foundations and they are very interested. They want to see some Phase I data first, so that's why we went ahead with the crowdfunding campaign to help us get to that point! Check it out: http://pledge.immunityproject.org http://pledge.immunityproject.org
- rposborne 13y ago
  Have any of them giving you all benchmarks to hit to secure funding?

lvryc 13y ago

They're also running a kickstarter-style crowdfunding attempt at https://pledge.immunityproject.org/the-free-hiv-aids-vaccine https://pledge.immunityproject.org/the-free-hiv-aids-vaccine .

icinnamon 13y ago
We are indeed!

rgejman 13y ago

Another thing I want to point out is that your home page touts safety as a design point. The text under "SAFE" says "Our vaccine does not contain killed viruses, live viruses, or genetically-modified viruses." I STRONGLY object to this language as it implies that inactivated (killed) and live* viruses are unsafe in general. This is simply not true. I believe most clinically used vaccines are either inactivated or attenuated. I understand that you're trying to make sure people understand that your vaccine is safe. However, implying that other vaccines are unsafe because they are inactivated or attenuated does a disservice to the entire vaccine industry. *I think you mean 'attenuated' here, not live

reidrubsamen 13y ago
Thanks for the comment! We did not mean to imply that existing vaccines were dangerous and will modify the language on the site to clarify.

kayhi 13y ago

Is there more basic research supporting this interaction (crystallographic or otherwise) between the peptide and T cell? The paper feels like to jumps right into animal models. "specific points identified by a data-driven analysis of actual individuals’ immune systems" pg1 What is the data in this case? What is the sequence of the peptide(s) that are incorporated into the PLGA? Side note: our start up works on helping biotech companies source reagents, supplies and equipment, we should be able to save you about ~15% on the ~475k part of the budget

naveenspark 13y ago
Naveen here from Immunity Project. Thanks for the question. We have not done receptor analysis. We are using animal models as our starting point - we are looking for an immune response with memory to the administered peptides - if we get that response in Phase I we should be in good shape! We received the peptides from researchers who have a manuscript in publication and would like us to keep the sequences confidential until they publish. Please see below for similar statistical research looking for targets to beneficial regions on HIV: Mothe B, Anuska L, Ibarrondo J, Daniels M, Miranda C, Zamarreno J, et al. Definition of the viral targets of protective HIV-1-specific T cell responses. Journal of Translational Medicine 2011;9(208):20. re: your startup / cost savings on reagents, supplies and equipment, we would love to talk to you about that. Please email us at team@immunityproject.org. Thanks!

ciokan 13y ago

I would be very curious to know if the team received any kind of pressure to stop what they're doing or if they will communicate if such thing would happen. Don't want to sound cynical, I just watched a lot on the subject recently and it seems there's a huge industry behind having a lot more benefits (material ones) from the actual sick people and their life-long expensive treatments compared to a vaccine. Even if it doesn't work God bless to you all for trying this. It's a wonderful thing to get you up in the morning.

naveenspark 13y ago
Thank you for the kind words and support! We are very focused on our stated goal which is ending HIV/AIDS with a free vaccine. We haven't received any pressure to stop our work yet. If we do we will definitely let you know so we can get your help in fighting back!
limpon 13y ago
I've heard lots of people speculating that the big pharma companies would be better of if there would always be HIV and they can sell their ART pills for live. But on the other hand if one of them is the first one to create a HIV immunization, this alone will make them so extremely rich. An effective HIV immunization will become standard immunization for all people in the western world and the WHO and UN will take all in their power to immunize as many people worldwide as possible. Just imagine the amount of doses that will have to be produced. And you would be the only one company having this product. This has way more financial gain that being one of the dozens of companies that produce ART therapies. On top of that a few people working in high positions of big pharma companies are still "nice" people who would actually be proud of curing a disease. Not everyone just counts their dollars every day and hopes that more people get sick.
- ciokan 13y ago
  yes but op website says they will release it for free, thats why i'm asking in the first place.