Wolf et al,
Thought that you might find these two articles interesting.
One talks about MS and an approach using something analogous to bee stings to upregulate IL10. It seems that when you upregulate IL10, the protein that causes the inappropriate cytokine expression decreases.
Interestingly, the description of the disease process in MS would seem to be taken care of by the intervention of WF10, to downregulate inappropriate inflammatory cytokine
The second reports on the likelihood of developing a vaccine for HIV -- conclusion of moderator of discussion -- not very likely.
Report:
Swiss bee-keepers hold key to MS vaccine
Investigators: David Wraith and Hartmut Wekerle
Friday Jul 27th, 2001
by John Bonner
Swiss bee-keepers are the unlikely source of evidence to suggest that a proposed new treatment for multiple sclerosis will work, said immunologist David Wraith from the University of Bristol, today. Wraith's team has been investigating ways of blocking the specific T cells that react to proteins of the protective myelin sheath surrounding nerve cells. The T cells produce inflammatory cytokines that mediate destruction of the protective sheath. He has been using synthetic peptides based on fragments of myelin protein to induce tolerance and stop the disastrous autoimmune response.
The approach has been successful in a laboratory model for human MS, experimental allergic encephalomyelitis. Repeated exposure to the peptides switches off the Th1 pathway, which generates T cells that produce tumor necrosis factor and other cytokines implicated in the inflammatory response in MS patients. Treated mice express a different T cell population, known as Th0, which produce the protective cytokine IL-10. This blocks any further autoimmune degeneration by preventing antigen presenting cells from activating new Th1 cells.
The peptides are squirted up the nostrils rather than given as an intravenous vaccine. This makes use of the mucosal immune response designed to prevent damaging inflammatory reactions to harmless antigens in the air and (in the gut mucosa) in food. "Most autoimmune diseases are inflammatory responses, and so we are tapping into the machinery which
has been specially designed to dampen down the inflammatory process,"
Wraith told BioMedNet News.
Even antigens that are otherwise harmful can be tolerated when presented to the immune system via the mucosal surface. Scientists in the mid-19th century described how native Americans had devised a way of preventing skin reactions to poison ivy by regularly eating the plant's leaves, Wraith
says.
But, Wraith needed evidence that the beneficial changes induced by the vaccine in mice could also be generated in humans. "It is all very well having an animal model. But before we could think of trying this approach
on patients, we needed evidence that people could produce the same type of T cells that generate the protective IL 10 response seen in mice."
That evidence came from a study of bee keepers in Switzerland, which showed that regular exposure to bee stings switches off allergic reactions - the bee-keeper's blood samples were rich in IL 10.
Wraith has an agreement in principle from the UK medicines licensing authority to begin trials in MS patients. These are likely to begin within the next year after completing the necessary pre-clinical safety tests.
Patients will probably receive a primary course of repeated weekly doses followed by monthly booster doses. He expects those patients in the early stages of the disease to benefit most.
Current treatments for MS do little more than treat the symptoms of the disease. Even the controversial beta interferon therapy works only in some patients and then only slows the progress of the disease. "We hope that we can shut the gate - this is the only treatment that gets to the heart
of the process that causes the disease," he said.
Other approaches to MS were also discussed at the meeting. One approach centers on switching off the inflammatory T cell response in the brain.
Hartmut Wekerle, head of the Department of Neuroimmunology at the Max Planck Institute of Neurobiology in Martinsried, Bavaria, who has pioneered the understanding of the T cell response in the disease, is involved in some of this work. He has investigated nerve growth factor, which appears to have anti-inflammatory properties, at least in a rat
model. Other approaches have used antibodies that prevent T cells from crossing the blood-brain barrier.
Wraith is keen keen to get clinical trials of his vaccine running as soon as possible. "We do have to be cautious because the last thing we want to do is to make things worse for the patients. But we have spent the past ten years investigating all the possible reasons why this approach may not work. I think it's time to bite the bullet."
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HIV Vaccine
Report:
HIV vaccination - more than a dream
Investigators: David Baltimore, Andrew McMichael, and Hans
Wigzell
Friday Jul 27th, 2001
by Melissa Mertl
A scheduled debate over whether HIV vaccination
was "an impossible dream" ended up with two
high-profiled scientists unwilling to take the
negative stance. Instead, they found common ground
on placing hopes on a vaccine that didn't actually clear the infection, but kept it at bay. It fell to the debate chair to add a note of caution.
"We don't know whether the notion of an HIV vaccine is an impossible dream," said David Baltimore, president of the California Institute of Technology (Caltech) and chair of the National Institutes of Health's HIV Advisory Board. Furthermore, he said, "we have absolutely no idea when
we will have a vaccine," adding that it could take at least five years but possibly decades.
Debate moderator Hans Wigzell, president of the Karolinska Institute and chair of the UN-WHO vaccine committee, listed a few reasons that one might argue to suggest the search is futile. No HIV infected individual has ever been known to clear away the virus from the body, and very few infected individuals fail to develop the disease. Recent studies from
uninfected prostitutes in Nairobi suggest that even those who have developed a cytotoxic T lymphocyte (CTL) response against HIV are not protected long-term. And finally, HIV vaccines tested so far in humans have not protected against infection.
"We need to make a vaccine using principles never before used to make vaccines," Baltimore said. We shouldn't expect a future vaccine to completely eradicate the virus
from the body, they agreed. A future vaccine "could give sterilizing immunicity produced by a pool of memory cells," said Baltimore. This could reduce the initial multiplication of HIV and allow a person to live with low levels of infection for the rest of their life without sickness. He
remarked that this was already possible in monkeys.
Since most existing vaccines have only activated an antibody response and proved disappointing in trials, "we should focus on T cell immunity," said Baltimore. A CTL-inducing vaccine would give a good burst of T cells to generate a long-term memory response, pointed out Andrew McMichael
from the John Radcliffe Hospital at the University of Oxford. McMichael and Baltimore agree that developing a vaccine that activates CTLs is certainly possible.
McMichael also stressed the importance of a vaccine's ability to take into account the diversity in HIV subtypes, or clades. "Even within a clade there is almost as much variability as between clades," he warned. Small
differences can mean the vaccine-induced CTL response will not recognize the virus. "We really have to have a vaccine with a broad response," he said.
The obstacles are not just scientific, he added. The political, regulatory, and ethical challenges need careful navigation. "The decisions we make now will affect us for the next ten years." The withdrawal of support
from developing countries could "put us back many, many years," said McMichael, a leader in the development of clinical HIV trials around the world. "Badly designed trials could end the dream."
In the light of general agreement, it was left to the debate chair, Wizgell, to represent the other side. "My personal belief," he said, "is that given the arrogance of the human species, it will be very long time, if ever, before a concept of an HIV vaccine will be considered impossible."
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My own opinion -- an AIDS vaccine will never be developed and even if it were, it will not produce any more positive effect than the natural human antibody response.
IMO the debate chair has more brains than any of the rest.
Best to all,
MB |
