The importance of Dr. Jonah Sacha’s late breaker at CROI
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Posted On: 02/10/2020 9:35:27 AM
Dr. Sacha and his group have been pioneers in the research for a vaccine for HIV.
They have developed and tested several T cell-based vaccine regimens and has done breakthrough findings in differentiating central memory T cells (Tcm) which live in the lymph nodes taking longer time to act, as opposed to effector T cells (Tem) that reside in the mucosal sites (lining of the lungs and colon, places where pathogens come into the body) where the body membranes and can perform its antiviral action almost immediately.
HIV, as depicted by Dr. Sacha has a window of vulnerability of 1-6 days and after that, peaking at around 14 days the virus has established himself in the host with a poor prognosis thereafter.
An trial (TEP) by Merck & Co (2003 – 2007) that attempted to test a vaccine that was designed to modify the disease course probably failed due to the fact that CD8+ Tcm where used (some argued that the vaccination actually increased the chances that some people would later acquire HIV). In basis of this Dr. Sacha, among other authors, has proposed a CD8+ Tem vaccine for HIV. What they did specifically, was to “create” CD4+ T cells that were predominantly polyfunctional, capable of production of MIP-1β (among others), this being a CCR5-binding chemokine that we know is capable of blocking HIV/SIV infection.
So, how all of this affects us? Apparently the team at Oregon University have advanced greatly in this area and have determined that a CCR5 blockade can protect from HIV (in macaques which have a good level of homology to HIV-1). This much we knew, however, PrEP trials are lengthy and results take long time to come by. A deterministic macaque confirmation by the Oregon group means a great deal, both, in terms of validation, and, also in terms of "trial" design.
This will mean a very good boost to Leronlimab as a viable PrEP drug; in Dr. Sacha’s own words:
Can’t wait to see the results of his tests in macaques and his take on Leronlimab as PrEP and a future vaccine.
They have developed and tested several T cell-based vaccine regimens and has done breakthrough findings in differentiating central memory T cells (Tcm) which live in the lymph nodes taking longer time to act, as opposed to effector T cells (Tem) that reside in the mucosal sites (lining of the lungs and colon, places where pathogens come into the body) where the body membranes and can perform its antiviral action almost immediately.
HIV, as depicted by Dr. Sacha has a window of vulnerability of 1-6 days and after that, peaking at around 14 days the virus has established himself in the host with a poor prognosis thereafter.
An trial (TEP) by Merck & Co (2003 – 2007) that attempted to test a vaccine that was designed to modify the disease course probably failed due to the fact that CD8+ Tcm where used (some argued that the vaccination actually increased the chances that some people would later acquire HIV). In basis of this Dr. Sacha, among other authors, has proposed a CD8+ Tem vaccine for HIV. What they did specifically, was to “create” CD4+ T cells that were predominantly polyfunctional, capable of production of MIP-1β (among others), this being a CCR5-binding chemokine that we know is capable of blocking HIV/SIV infection.
So, how all of this affects us? Apparently the team at Oregon University have advanced greatly in this area and have determined that a CCR5 blockade can protect from HIV (in macaques which have a good level of homology to HIV-1). This much we knew, however, PrEP trials are lengthy and results take long time to come by. A deterministic macaque confirmation by the Oregon group means a great deal, both, in terms of validation, and, also in terms of "trial" design.
This will mean a very good boost to Leronlimab as a viable PrEP drug; in Dr. Sacha’s own words:
Quote:
"In the absence of a prophylactic vaccine, the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition by uninfected individuals is a promising approach to slowing the epidemic. Unfortunately, negative side effects, viral resistance, and regimen adherence severely limit PrEP efficacy. Therefore, the development of new, highly effective, and long-acting PrEP modalities with high patient uptake is urgently needed. The scientific premise for leronlimab-based PrEP is founded on the long-standing observation that CCR5-deficient individuals are extremely resistant to HIV infection. The results presented here demonstrate that leronlimab treatment is able to prevent sexual transmission of HIV. Given leronlimab's excellent safety profile, this finding paves the way for a new, patient-friendly PrEP regimen."
Can’t wait to see the results of his tests in macaques and his take on Leronlimab as PrEP and a future vaccine.
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