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$$$ CRUCELL H2 2007 $$$

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  2. [verwijderd] 16 november 2007 09:49

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    Uit 2006.
    AIDS Vaccine: Lack Of Planning On Vectors Risks Future Public Health Gains

    Keith Alcorn, Tuesday, September 5, 2006


    A lack of coordination in the international vaccine development field could jeopardise the implementation of a series of much needed new vaccines for developing countries, according to a leading virologist speaking last week at AIDS Vaccine’06 in Amsterdam. Professor Jaap Goudsmit of the University of Amsterdam warned that the current enthusiasm for using adenoviruses as vectors for various vaccines - including HIV - could sabotage the sequential introduction of vaccines for malaria, tuberculosis (TB) and HIV, especially if the wrong strains of adenovirus are used.

    Viral vectors for vaccine delivery are being explored because it is not currently thought possible to deliver a live attenuated form of HIV as a vaccine in the way that some other viral diseases are countered.

    Instead, researchers are using modified viruses such as pox viruses and adenoviruses to carry HIV genes that will stimulate an immune response. The most advanced vaccines, those under development by Merck and by the US government’s research programmes, are using adenoviruses or canary pox virus.

    Adenoviruses, which cause common cold symptoms, are strong stimulators of immune responses and also strongly express the genes implanted into them. They can be delivered by a wide variety of routes, including orally or intranasally, and are easy to grow.

    But viral vectors are not without their drawbacks. The problem with adenoviruses is that lots of people have immunity to types of adenovirus. Up to 80% of the population in some developing countries may have some degree of immunity to adenovirus type 5, the strain being used in the Merck vaccine. A second adenovirus-based vaccine, now in trials sponsored by the HIV Vaccine Trials Network, is being evaluated in a variety of populations to see whether pre-existing immunity makes any difference to response, and whether immunity to particular adenovirus `serotypes` has an effect on response.

    Researchers at Harvard Medical School are currently pursuing a strategy to disguise adenovirus type 5 from the immune system by stripping out the antibody-targeted regions of the spikes on the adenovirus envelope and replacing them with similar sequences from a very rare form of adenovirus. Dan Barouch and colleagues reported earlier this year in Nature that this vector was successful in overcoming pre-existing adenovirus 5 immunity in animals.

    However, Robin Isaacs of Merck says that human studies conducted so far with the company’s adenovirus-based vaccine have not shown any effect of pre-existing immunity on vaccine responses, even at very high adenovirus antibody titres.

    Nevertheless, Professor Goudsmit warns that the current vogue for exploring adenovirus vectors may have another downside.

    “In the vaccines field there are trends – at one time it was pox-based vectors, now it’s adenoviruses. We need to pay attention to the risk of vector fatigue – you cannot use the same vector for another vaccination.”

    In particular, Professor Goudsmit is concerned by the potential for HIV, TB and malaria vaccines to interfere with one another. Researchers at the conference estimate that a vaccine against infant malaria might be achievable within five years and a TB vaccine within ten years.

    Paradoxically the company in which Professor Goudsmit serves at Chief Scientific Officer, Crucell, is itself pursuing an adenovirus vector for a malaria vaccine, using the rare Ad35 serotype. Crucell is also being funded to develop a TB vaccine based on an Ad35 vector by the Aeras Global TB Vaccine Foundation, and its technology is also being used in the development of Merck’s Ad5-based vaccine. The company is also being funded to develop two adenovirus vectors – serotypes 11 and 35 – by the International AIDS Vaccine Initiative, using non-human primate-derived adenoviruses.

    Isn’t it a bit late for the company’s own Chief Scientific Officer to be raising the alarm over an issue where his company sits right in the middle?

    Crucell argues that its adenovirus-based vaccine efforts, like those of other research groups, are designed to identify rare serotypes and non-human primate adenoviruses that can be used to complement each other in the array of vaccines now in development for poverty-related communicable diseases.

    But Crucell has another strategy too, it seems. The company recently bought Swiss-based Berna Biotech, where the emphasis of vaccine vector research has been on measles virus. Hussein Naim of Berna showed the AIDS Vaccine ’06 conference that even though measles virus is a common childhood vaccination, a recombinant measles virus serving as vector for a SARS vaccine was able to induce strong cellular immune responses in people with pre-existing immunity to measles virus at the background antibody titre found in the North American population.

    The critical test for HIV vaccination will come in the two proof of concept phase IIb trials now being carried out with adenovirus-based vaccinations, but these studies will be unable to answer for the consequences of other adenovirus-based vaccines, such as the malaria vaccine already being explored by the US Naval Medical Research Center and the Malaria Vaccine Initiative, and the Walter Reed Army Institute malaria vaccine being developed in collaboration with Glaxo SmithKline.
    http://www.aidsmap.com/en/news/4C2522D5-CE46-4571-BC49-CF52C9B05046.asp
    Japie
  3. [verwijderd] 16 november 2007 09:49

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    Merck halted clinical trials of its vaccine in September, and last week researchers said that a cold virus used in the shot may have made test subjects more likely to catch HIV. The finding may cause the U.S. to cancel a study of a similar vaccine and raises concern about projects at Crucell NV.

    ``This is really urgent right now,'' Walker said in a telephone interview. ``There are a lot of vaccines in the pipeline that are adenovirus-based, and we have to figure out what happened here.''

    Crucell's vaccine is designed to avoid immune interactions like the one in the trial, said Jaap Goudsmit, the company's chief science officer. Crucell, based in Leiden, the Netherlands, is developing vaccines against tuberculosis and malaria that use other strains of adenovirus. The company's shares have fallen 5.2 percent since the announcement about the cold virus last week.
    Concerns about safety have pushed back a trial of a government-developed vaccine that contains adenovirus. The U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, will hold a meeting of researchers Dec. 12 to determine whether or how to proceed with the vaccine trial.

    `Very Conflicted'

    The adenovirus in the government's vaccine is genetically different from the one in the Merck trial, and plays a much smaller role in immunization, said Gary Nabel, director of the Vaccine Research Center at the U.S. National Institutes of Health in Bethesda, Maryland, and the vaccine's developer. The threat of HIV makes it crucial to test the vaccine if possible, he said.

    http://www.bloomberg.com/apps/news?pid=20601100&sid=awFBgxtS9qho&refer=germany

    http://crucell.yourbb.nl/viewtopic.php?t=24&start=120
    Japie
  14. [verwijderd] 16 november 2007 10:01

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    Crucell's vaccine is designed to avoid immune interactions like the one in the trial, said Jaap Goudsmit, the company's chief science officer. Crucell, based in Leiden, the Netherlands, is developing vaccines against tuberculosis and malaria that use other strains of adenovirus

  18. [verwijderd] 16 november 2007 10:04

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    potverdorie slimmie, ik post hier alleen berichten en ik laat me verder niet uit qua interpretatie.
    mij hoor je wel zeggen dat de daling waarschijnlijk komt door de onzekerheid rondom adenovirussen. Heb jij een andere reden aan te wijzen voor deze dalingen de laatste dagen?
    Japie
  20. [verwijderd] 16 november 2007 10:04

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    ``This is really urgent right now,'' Walker said in a telephone interview. ``There are a lot of vaccines in the pipeline that are adenovirus-based, and we have to figure out what happened here.''
    Japie
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