POZ Community Forums
Meds, Mind, Body & Benefits => Research News & Studies => Topic started by: bimazek on September 23, 2007, 08:06:51 pm
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A dendritic cell-based vaccine for treating HIV infection: background and preliminary results
i have wanted to post on this for a year... read the links and the highlights below...
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2796.2006.01738.x
February 2007
our therapeutic vaccine should next be tested on patients who are resistant to ART as well as on the large number who would like to stop ART.
JM Andrieu, W Lu - Journal of Internal Medicine, 2007 - Blackwell Synergy
... 1 Zinkernagel RM. Immunity, immunopathology and vaccines against HIV? Vaccine 2002;
20: 1913–7. 2 Centers for Disease Control and Prevention (CDC). ...
A year following vaccination, 8 patients had a plasma viral load decrease >90%; among them, 4 had viral load <1000 copies mL-1. Moreover, by one year, the viral load decline of the 18 patients was significantly correlated with their percentage of HIV-1-gag-specific CD8+ T cells expressing perforin and that of HIV-1-specific CD4+ TH1 cells. This is the first demonstration of the capacity of a therapeutic vaccine to induce an effective HIV-specific T cell response associated with sustained viral suppression in untreated viremic patients. The manipulation of antigen presenting cells to elicit virus-specific cellular responses is a promising tool to control persistant viral infections.
I have wanted to post on this for a year DC vaccines but this new new article is very interesting
good responses
a gay pdD guy i talked to online said he feels dendritic cell vaccines are going to be a big growth area and such
there is so much good stuff in this long article...
http://www.blackwell-synergy.com/action/showFullText?submitFullText=Full+Text+HTML&doi=10.1111%2Fj.1365-2796.2006.01738.x
HIV-1 is now more and more frequently viewed as a poorly cytopathic virus by many immunologists
The administration of an efficient therapeutic vaccine (probably to be repeated every year or every 2 years) to HIV-infected patients should (if successful) lead to a decrease in viral replication and release. This would result in the stabilization/partial reconstitution of the immune system allowing vaccinated patients to avoid or postpone ARTs
Four months after the first vaccination, the median PVL of the 18 patients decreased by 80% (P < 0.01) and their CD4 lymphocytes count stabilized. A year after the first vaccination, viral concentration decreased by more than 90% in 8 of the 18 patients.
Transient viral infections caused by cytopathic viruses like smallpox or poliomyelitis
Persistent viral infections like the herpes simplex 1 and 2 (HHV1 and 2) or the varicella/zoster virus (HHV3) infections are caused by intermittent cytopathic viruses. After the primary infection, the replication of these viruses inside their target cells is strongly controlled by the permanent pressure of specific T cells which maintain them in a so-called state of latency. In fact, as soon as there is a transient or more prolonged weakness, disturbance or loss of anti-viral immune functions (whether provoked by ageing, immunosuppressive therapies or immunosuppressive infections), these viruses resume their replication with their associated cytopathic effects (before being controlled again or not depending on the level of impairment of the immune system).
Persistent viral infections caused by poorly/noncytopathic viruses include two devastating viruses: the hepatitis B virus (HBV) and the hepatitis C virus (HCV). The immune system exerts a strong control on viral replication in the majority of individuals who have acquired HBV. However, it is not effective enough in a minority of them and in almost all patients with HCV with the consequence that the viral replication in infected cells and measurable viral release in the extracellular milieu persist for life. This is also the case of the human immunodeficiency virus -1 (HIV-1) which is now more and more frequently viewed as a poorly cytopathic virus by many immunologists [1], although it has been considered for a long time as a cytopathic virus by virologists. Importantly, cellular damages provoked by these three persistent infections do not directly result from viral replication but from immunopathology associated with the chronic release of the virus and inadequate response of the immune system
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18 people is too small a sample. Besides, there is no control group, which makes any "scientific" conclusion impossible.
The second phase of this study was scheduled to begin in april 2007, with 40 volunteers, this time not only from Brazil, but from also from France, Belgium and the USA. The aim now would be to standardize the dosage and higher the potence of the treatment..Still no news from this second phase, which should take up to 2 years to be concluded.
I cannot understand, if results from the first phase of the study in 2004 were so astounding as it seems, why the second phase of the study began only in 2007??
The brazilian responsible for conducting the trials in Brazil (Mr. Luiz Cláudio Arraes) said that the production of the vaccine in commercial scale is still unthinkable due to the high costs of the logisticc involved , and that the final phase of this study would still take something between 7 and 10 years. They classify the study as "promising". In a piece of news from last week the brazilian researcher said that the study was halted in 2004 due to lack of funding (?!). It also says that have only 7 volunteers at the moment aand are still recruiting. It also says that the french researchers are no longer in the study. This is all very strange.
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http://www.arcat-sante.org/actus/109/Vaccin_therapeutique_retour_sur_un_effet_d_annonce
Do not want to sound downbeat, but if anybody can read french, the link above can be useful in terms of putting the study conducted in Brazil in 2004 in a more realistic perspective.
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Hi Ron,
Don't worry about sounding "downbeat". If this vaccine isn't realistically going to be anywhere near ready for what sounds like as many as 15 years, then we need to be aware of that and not get hopes up.
I like my hopes to be tempered with realism.
And at times like these, I wish I could do the French thing.
Ann
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This report (http://www.webmd.com/hiv-aids/news/20041129/human-test-novel-vaccine-stops-hiv) covers the key parts of the French one (pls ignore the sub-ed's title "Human Test: Novel Vaccine Stops HIV" and naff opening para.
The essentials:
"Wei Lu, Jean-Marie Andrieu, and colleagues at the University of Paris in France and Pernambuco Federal University in Recife, Brazil, tested the vaccine on 18 Brazilian patients. All had HIV infection for at least a year. Their T-cell counts -- a crucial measure of AIDS progression -- were dropping, meaning their disease was worsening. None was taking anti-HIV medications.
"After getting three under-the-skin injections of the tailor-made vaccine, the amount of HIV in the patients' blood (called the viral load) dropped by 80%. After a year, eight of the 18 patients still had a 90% drop in HIV levels. All patients' T-cell counts stopped dropping.
Results published in Nature mag...
bit later Andrieu is reported as saying:
"'The results suggest that [these] vaccines could be a promising strategy for treating people with chronic HIV infection,' Andrieu and colleagues write. 'The significant decrease of viral load as well as maintenance of ... [T-]cell counts observed at one year after immunization are particularly promising.'"
Promising, proof of concept, come back in 5 years (hope and realism in equal measure me...)
- matt
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The French article does reiterate what we've read in the English press release but warns that the announcement was premature, as the vaccine was tested on too few people and and that, in order to be valid, it would require a randomized trial with an appropriate control group.
The article also heavily criticizes Dr. Andrieu for having stated something to the effect that four of the patients saw their viral loads drop to below 1,000 copies/ml, which made them "in principle, not contagious" because this false assertion could lead cause people to have unprotected sex. The TRT-5 (a group of therapeutic research and treatment associations) has condemned what its members see as "irresponsible media and a guilty scientist"-Dr. Andrieu-because the safety and effectiveness of the vaccine have not yet been proven and because one of the basic principles of medical ethics-not to do harm-was not followed in this instance. They reiterate that "so far, no vaccine has been able to prevent or to treat HIV infection. The only proven means of preventing the sexual transmission of HIV has been the condom, male or female."
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That's odd I thought I posted the translation already.
/edited to remove the translation and add:/ never mind newt&jake already posted the gist of it.
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[double post]
damn timeouts
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If money is an issue for developing this vaccine, hopefully the publication will attract investors. Perhaps some big pharma with mucho capital will buy the development rights and escalate the development process. The initial reports of small numbers benefiting are the magnets for the development money. And, the publication of these early results may spur interest in this field.
Side effects, known or emerging in the future, are major challenges for long term survival. Immune stimulating treatments, without/minimal side effects, are attractive and hopeful to me.
Thanks for the info Biz. Hank
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hook on clinicaltrial.gov and type
LC002,
this is the vaccine that you talk about.
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hook on clinicaltrial.gov and type
LC002,
this is the vaccine that you talk about.
It is not the same vaccine. The french vaccine was custom-made for each person, based on dendritic cell extracted from the volunteers.It seems that the chief researcher, Mr Jean Marie Andrieu, has a bad reputation for making public his "achievements" with little care to scientific rigour. He was involved in a similar case 2 decades ago, concerning a chemical named cyclosporine.
The fact that there was no follow-up study since 2004, that the french are no longer in the project and that no private company showed any interest in financing this french-brazilian vaccine says it all. Forget about this french/brazilian vaccine.
But in the site you mentioned, i have been able to identify two strials involving vaccines made based on the same method used in the french-brazilian vaccine.
http://clinicaltrial.gov/ct/show/NCT00510497;jsessionid=54C3D26142946BB6EA4C8B04E1FF0EC3?order=26
http://clinicaltrial.gov/ct/show/NCT00402142;jsessionid=54C3D26142946BB6EA4C8B04E1FF0EC3?order=10
Let us wait and see the results.