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How could a therapeutic vaccine work?
Mar 24, 2002

I have been reading a lot about therapeutic vaccines to treat those of us who are already infected. I wonder how this could possibly work? If the real HIV we have in our bodies can't stimulate the production of "killer T-cells", how could a vaccine, which would be a neutered form of the virus, fake-out our immune system?

Response from Dr. Cohen

Great question. One that researchers who don't do vaccine work wondered about for years while this research was getting started.

Here is the key insight. You are correct - HIV is plentiful in those with ongoing viremia (a detectable viral load). And this amount of HIV is not leading to a protective response - the immune system suffers from this onslaught. But - there are a few people who have HIV and who are long term nonprogressors (or very slow progressors) who have an immune system that does control HIV for years and even decades. And what is different about them is in part for some reason they were able to mount an effective immune response to HIV that works for years. And researchers have been working to understand what constitutes this success - it appears to be in part an effective T helper response directed against HIV. Sadly, the T helper cells are the ones targeted for infection/destruction by HIV - and again for reasons that are unclear, only a few emerge from that initial battle during seroconversion with these cells at levels that are able to do the job. Most emerge with these cells depleted.

So the key for a vaccine is to now reeducate the immune system to do what these few can do on their own - control HIV infection. And since our antivirals can control HIV - and allow the immune cells to recover from the ongoing struggle against HIV - we hope that a vaccine can take this now healthier immune system, and help focus its efforts on controlling HIV in a way it didn't figure out on its own. In part by stimulating a more effective cellular response that can control HIV.

All of this may be possible - indeed, there are animal studies that are very encouraging, and some studies in people that are supportive. But this is not easy to do clearly - we have been working on therapeutic vaccines for about a decade and still have at best hints and early observations. But there is continued work and optimism - the next few years may show far more exciting results...

Hope that helps.



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