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Dendritic Cell-Based Vaccines

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Markmt:
These last few months have been amazing with so many reliable breakthroughs from all over the world. California, San Antonio, Canada, Japan, Spain, France Switzerland, SouthAfrica and so on!... While its good to keep feet on the ground it really seems like its all heading in the right direction, with very interesting years ahead. All fingers crossed. 

Mishma:
I can not recommended enough a Immnology Textbook I've been reading for the last 20+ years and now in its Seventh Edition: Cellular and Molecular Immunology by Abul K Abbas, Andrew Lichtman and Shiv Pillai ISBN: 978-1-4377-1528-6. The book is used for  first or second year  medical students throughout the US. Besides being a fantastic textbook with great graphics, the book is a great reference book. For example you might wonder, what the heck is a Dendritic cell and where did it come from?

Another reference to Dendritic Cells and their function in spreading HIV to CD4 cells comes from the front page of POZ News:
http://www.sciencedaily.com/releases/2012/12/121218203506.htm

elf:
Well, dendritic cells are antigen-presenting cells,
CD4+-receptor cells, the main responsible for acquiring of HIV infection during anal sex.
(That's why you don't need blood at all (where other CD4+ cells like CD4+T-lymphocytes, or monocytes are) to get infected, even a tiniest tear in rectal mucosa can ''expose'' the dendritic cells)


http://en.wikipedia.org/wiki/Antigen-presenting_cell

YellowFever:
heat-inactivated HIV? If only cure therapy was as simple as eating cooked HIV....

Mishma:
Another story on this same proof of concept study:

http://www.medpagetoday.com/HIVAIDS/HIVAIDS/36686?ic=700100

Therapeutic HIV Vaccine Shows Promise
By Michael Smith, North American Correspondent, MedPage Today
Published: January 03, 2013
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points
An experimental therapeutic vaccine against HIV was able temporarily to lower the level of virus in the blood of infected volunteers.
Note that although the effect did not persist, it is "proof of concept" that such a vaccine might lead to what is called a functional cure, defined as control of HIV replication without antiretroviral drugs.
An experimental therapeutic vaccine against HIV was able temporarily to lower the level of virus in the blood of infected volunteers, researchers reported.

In a randomized, blinded, placebo-controlled trial, the vaccine using modified antigen-presenting dendritic cells lowered the so-called viral set point for several months, according to Felipe Garcia, MD, of Spain's University of Barcelona in Barcelona, and colleagues.

Although the effect did not persist, it is "proof of concept" that such a vaccine might lead to what is called a functional cure, defined as control of HIV replication without antiretroviral drugs, Garcia and colleagues concluded online in Science Translational Medicine.

Such control is already seen in the small minority of HIV-positive people known as "elite controllers," whose immune systems are able to keep the virus in check for decades without the aid of drugs, the researchers noted.

The new findings "open the possibility that a therapeutic vaccine could be used as a strategy to obtain a functional cure," Garcia said in a video interview with the journal.

Dendritic cells play a key role in the immune response to infectious disease, presenting antigens to the T cells so that they can identify the invading pathogens.

But in HIV infection, the dendritic cells can also carry live virus to the CD4-positive T cells, causing them to die instead of mount an immune response, Garcia and colleagues noted.

To avoid that in this study, they pulsed the patients' own monocyte-derived dendritic cells with virus collected from their blood and rendered inactive with heat.

The 36 patients were all on long-term combined antiretroviral therapy; 24 were randomly assigned to get three injections of the HIV pulsed cells and 12 to get three shots of unmodified cells.

Antiretroviral therapy was then stopped, and the patients were followed for up to 48 weeks.

The goal was to see if the vaccine lowered the plasma viral set point of HIV from a baseline established during an earlier interruption of therapy, Garcia and colleagues reported.

The vaccine was safe, they reported, and well tolerated; the main adverse effects were asymptomatic lymph node enlargement in four patients and one case each of local redness at the injection site and flu-like symptoms.

On the other hand, several patients in each arm had to resume therapy when their CD4 cell count dropped below prespecified levels.

Twelve weeks after antiretroviral drugs were stopped, 12 of 22 patients remaining in the active arm had at least a 10-fold reduction in the plasma viral load set point, compared with one of 11 in the control arm. The difference was significant at P=0.02.

After another 12 weeks, seven of the 20 remaining patients in the active arm still had at least a 10-fold drop in the viral load set point, compared with none of the remaining 10 patients in the control arm. The difference was significant at P=0.03.

The decrease in plasma viral load was associated with increases in HIV-specific T cell responses, Garcia and colleagues reported.

Despite the declines, however, viral load rebounded to detectable levels in all patients.

Garcia and colleagues cautioned that the goal of any therapeutic vaccine would be to keep viral load undetectable without the use of drugs and "this objective has not been reached with this vaccine."

One possible reason is that the patients were off medication for several weeks about 12 months before the first shot, in order to allow the collection of autologous cells and virus. That, Garcia and colleagues argued, might have "compromised the results" by allowing viral replication despite a subsequent drop to below the level of detectability.

Also, they noted, the vaccine did not prevent a drop in CD4 cells, which meant that several vaccinated patients had to resume therapy.

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