Immunity Project – HIV Vaccine Development Program [pdf]

Hi there, Reid from Immunity Project. Thanks for the great question! Would love to talk with you off line about your research, by the way.

1. We have successfully gotten an immune response with memory (by elispot) after a single dose of the PLGA microspheres containing one or two peptides when combined with TLR-4 (MPLA) and TLR-9 (CpG) agonists. We used H2d restricted epitopes to do the study in C57BL/6 mice – this study is done and in the PRJ review process. We are being careful about posting the results in the event we need to re-submit to a journal who would get heartburn if they saw the data posted.

2. We are raising money now to essentially repeat the experiment (on a smaller scale because we think we understand the optimal formulation configuration now) in C57BL/6 NOG mice (with human PBMCs grafted in from a donor with known HLA type). The new experiment starts off looking like the experiment in (1) above: intradermal tail injection, wait 14 days, sacrifice, get the spleen, confirm immune response to peptide target by flurospot. The next part is new: separate CD8 from CD4 cells (from the mouse spleen), infect the CD4 cells with HIV, see if the vaccination attempt was good enough to see p24 antigen suppression and/or a change in the CD4 counts (all in-vitro). We can finish this study in a couple months, assuming the crowd funding keeps going well and we start in a couple weeks. We will use a different mechanism to publish our paper around this experiment so that we can get it out right away in a fashion that will lead to peer review and open access (We just learned about peerj.com – thoughts on that?).

Looking forward to hearing your thoughts on our approach.

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

Wait! But what HIV protein(s) is the peptide(s) derived from?

Let's not overlook the decades of prior data! The field is littered with names like VRC01, Camelid and so many other players. I know, I know, antibodies all versus antigen in this case. But keep reading ...

HIV is a master at developing resistant forms of itself. What if it changes the epitope and evades the vaccine induced antibody(ies), again!?! (Edit: Don't forget the long-term viral reservoirs that survive against the best antiretrovirals known to us!)

This is something I care about personally: What is their strategy against resistance? (Or, like everyone else before them, they will build that bridge when the water is above their nose!?! Not being snarky, just very concerned.)

And might I also ask: Any concerns about accidentally inducing an autoimmune disorder with that antigen/epitope? Why/why not?

Added: I'd love to see these guys succeed and really want to see a rationale and approach that goes beyond what has been tried and not worked so far. Also, kudos for the open-science approach!

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.

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.