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nmbasdf105 karma

Four questions:

1) How is your approach different from other HIV T cell-inducing vaccines (http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0030157, http://www.ncbi.nlm.nih.gov/pubmed/24166483, http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0086254 among others) that likely include the same conserved regions that you intend to target?

2) If your immutable region of the virus proteome is small, what is the likelihood that the majority of the population will have HLA class I molecules that can bind peptides derived from this region?

3) What do you mean when you say the vaccine will be free? That there will be no royalties or patents? That it can be manufactured by any group free of charge without licensing? That all components of the vaccine will be gifted from the supplier?

4) From 2000-2010, there are hundreds of articles describing HIV-specific T cell responses in general and immune responses mounted by HIV controllers in particular. How is your approach distinct from and superior to these studies?


nmbasdf55 karma

Thanks for the answers - can I ask a few followups?

1) Is there any evidence from any system (HIV/other viruses where T cell responses are important for control but are not as variable as HIV) that a single T cell epitope can confer protection?

2) Fair enough, but wouldn't this mean that you would need different formulations for different parts of the world where HLA types are different? Are the different clades of HIV found in different parts of the world completely sequence identical in any part of the viral genome?

3) Couldn't the same claim be made for anything whose delivery to end-users is completely subsidized by someone else (e.g., I want to build a "free cell phone", but it is only free if someone else pays for it)? Can you also comment on licensing? Are all the components of the vaccine free-to-use and manufacture by anyone, including generics manufacturers?

Thanks again!

nmbasdf42 karma

I am pretty sure that you are not the first group to try immunizing to elicit T cell responses against individual epitopes.

The responses you hope to elicit might be different in that they are constrained against varying during natural infection, but this does not necessarily mean that these responses are going to be protective and have a potent effect in vivo.

Said another way, what is the data that these responses are protective?

If you need to make a 'master' vaccine that covers all clades, instead of a single vaccine that covers all clades, does that not mean that the regions you are targeting are variable, at least on a global scale?

I do like your innovative approach to pursuing funding. And you have a laudable goal. But several of your answers on this thread and in your press interviews are wrong (e.g., Nature and Science do not publish "specialist" articles on HIV vaccines - this is simply untrue) or could be miscontrued (e.g., what exactly you will know at the end of your phase I study - isn't it just safety and whether you raise an immune response, NOT whether the vaccine "works" at converting people into controllers?)

nmbasdf9 karma

Yes, there is. Phase I trials are not powered to resolve significant differences in effectiveness between vaccine recipients and controls. Phase 1 trials have between 20-100 participants. Say 10% of these participants become HIV infected during the trial (exceptionally high, but still), that's 2-10 infections. Not nearly enough to say anything meaningful about efficacy. That's way phase I trials are designed to measure safety primarily (http://www.hvtn.org/science/phases.html).