Montreal is a cold place, unlike Southern California. The Canadians are very nice and friendly people. The meeting is very organized and contrary to Mexico City, my hotel is within walking distance of the convention center. It is walking underground where there is a tunnel system.The first session I went to is the young investigators session. I don't feel particularly young or smart compared to the young people, mostly from the east coast here. But i got up early just like the good old days and started learning.
The first session I went to was the immunopathogenesis of HIV. As most people know by now, that HIV attacks the GI system first. There is a rapid depletion of CD 4 cells right when the virus infects, and a translocation of microbe from the mucosa of the GI tract into the blood stream. This leads to immune activation, the characteristic first step and later problem with HIV infection. An excellent marker of this going on is LTS levels in the blood. This immune activation leads to a fall in the viral load immediately, a time when some people say is to knock out the virus. Yet no one has yet done that, because with few exceptions, no one knows within hours when they are infected. The immune activation leads to a cascade of other immunopathogenic steps and HIV infection is well established.
Then the talk turned to pathogenesis of HIV in the brain. The brain is a sanctuary and a reservoir of HIV infection. Untreated HIV infection in the brain leads to HIV Dementia something not seen often now with antiretroviral drugs so effective but is something that some people are worried about for long term survivors of HIV. The first cell infected is the monocyte of the brain as the virus crosses the blood brain barrier easily. Monocytes infect dendrites and the process continues. There is a disproportionately low amount of virus in the brain compared to the amount of inflammation that is going on. Attacking the brain as a reservoir and sanctuary is one of the main reasons that current antiretroviral drugs have failed to eradicate the virus.
The next talk I heard was about vaccines and immunology. The presenter talked first about why the famous STEP vaccine failed now 16 months ago which basically called a halt to all vaccines without new ideas and research, and the promising thing is that is starting to happen now, and especially with the new administration, more money will be available for vaccine research.
But there are 3 main reasons why the Step vaccine failed:
The first one which researchers are concentrating ion is the adenovirus vector. It now is clear that those people hat had been exposed to the adenovirus before, most people, developed immunity to the adenovirus before, had antibodies to it, and when the adenovirus was used in the step vaccine there was a failure to produce neutralizing antibodies to the vaccine because those people who had already been exposed and had developed antibodies to the adenovirus, now failed to produce the most important neutralizing antibodies necessary to get protection from HIV. Seems simple now but no one thought about it before the trial started.
The second major reason the vaccine failed, was because it was a dead virus that was used, and except for one type of polio virus vaccine, all other successful viruses used in good vaccines have been live attenuated viruses. The problem with this is that the regulatory bodies will not allow a live attenuated virus to be used in trials. That is too bad. With the case of the live attenuated virus that was used in the final polio vaccine no one got polio, and probably no one would get HIV from a live attenuated virus. Again bad thinking on the part of the regulatory bodies.
The third reason the step virus failed was that it failed to consider the different type of HIV viruses in Africa, another words the subtypes.I asked the above 2 questions and the presenter said people are now working in that also. Vaccines for HIV are a long way off and finding a drug that can eradicate the virus is more promising.These sessions were very good as they were open to questions, and the young investigators present often baffled the presenter with very intelligent questions.
For More News From Peter Schick: http://www.schickresearch.com/
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