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  1. [verwijderd] 19 januari 2007 22:17
    Ha die Flosz,

    Weer goed getraceerd.
    Ik blijf erbij, je wordt binnenkort door een head-hunter ontdekt en we zijn je kwijt bij het forum.

    Het zij je van harte gegunt!

  2. [verwijderd] 20 januari 2007 09:52
    Strijd tegen malaria krijgt 250 miljoen
    Van onze verslaggever Olav Velthuis

    AMSTERDAM - De strijd tegen malaria krijgt een forse financiële impuls. Nog dit jaar wordt een wereldwijd fonds opgericht dat jaarlijks 250 miljoen dollar moet gaan verstrekken. Dat zijn vertegenwoordigers uit ontwikkelingslanden, rijke landen, de Wereldbank en de ontwikkelingsorganisaties afgelopen week in Amsterdam overeengekomen.

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    UitlegVolgens Kenneth Arrow, Nobelprijswinnaar in de economie en bedenker van het plan, zijn subsidies de enige mogelijkheid om malariamedicijnen betaalbaar te maken voor getroffenen.

    Jaarlijks overlijden meer dan een miljoen mensen aan malaria. Het overgrote deel van de slachtoffers zijn kinderen. ‘Oude medicijnen hebben de afgelopen decennia hun werking verloren’, zegt Arrow. De malariamug is daartegen resistent geworden. ‘Maar die medicijnen waren wel overal in de dorpssupermarkt verkrijgbaar, voor doorgaans niet meer dan 10 cent.

    Een nieuw medicijn bestaat inmiddels, maar dat is minstens tien tot twintig keer zo duur. In Kenia, bijvoorbeeld, moeten mensen bijna vijf dagen werken om een behandeling met het nieuwe medicijn te betalen.

    Een nieuw fonds moet het prijsverschil tussen het oude en het nieuwe medicijn gaan vergoeden. Overheden, ontwikkelingsorganisaties of groothandels zouden het malariamedicijn dan tegen gereduceerd tarief inkopen bij medicijnfabrikanten zoals het Zwitserse Novartis. ‘Voor de rest van het bedrag stuurt Novartis vervolgens een rekening naar het subsidiefonds’, zegt Andreas Seiter, gezondheidsexpert bij de Wereldbank. Het fonds gaat maximaal 250 miljoen dollar per jaar verdelen, waarmee 350 miljoen gevallen van malaria behandeld kunnen worden. Onduidelijk is nog of voor het fonds een aparte organisatie moet worden opgericht.

    ‘Wij springen een gat in de lucht met zo’n subsidiefonds’, zegt Eyitayo Lambo, de Nigeriaanse minister van Gezondheid. Volgens Rob de Vos, een hoge ambtenaar van het Nederlandse ministerie van Buitenlandse Zaken, is geld niet het probleem. Het bedrag wordt hoofdzakelijk door rijke landen, maar in mindere mate ook door ontwikkelingslanden opgebracht.

    Bovendien kan van nieuwe financieringsmechanismen gebruikt worden gemaakt, zoals een luchtvaartbelasting die enkele landen vorig jaar invoerden om medicijnen voor ontwikkelingslanden uit te bekostigen. Ook valt te denken aan de uitgifte van obligaties. Engeland haalde met zo’n systeem dit najaar al geld op voor immunisatieprogramma’s in ontwikkelingslanden.

    Niettemin zitten er haken en ogen aan het subsidiefonds. ‘Het gevaar bestaat dat de pillen helemaal nooit op het platteland aankomen’, zegt Arrow. Ook zouden bedrijven die de pillen goedkoop met subsidie inkopen ze duur kunnen doorverkopen. Volgens Arrow moet concurrentie op de vrije markt dat voorkomen.

    Seiter wil daarnaast dat controle wordt uitgeoefend bij de distributie van de pillen. Daarbij kan worden meegelift op het controleapparaat van onder meer de Clinton Foundation, de ontwikkelingsorganisatie van Bill Clinton.

    De strijd tegen dodelijke ziekten die vooral ontwikkelingslanden treffen – behalve malaria, tuberculose, aids – is de afgelopen jaren mede door toedoen van Bill Clinton en Microsoft-oprichter Bill Gates op de agenda gezet.

    Volgens Olusoji Adeyi van de Wereldbank zijn malariapillen maar een deel van de oplossing. ‘We moeten ook voorkomen dat mensen malaria oplopen, door te blijven investeren in klamboes en in insecticiden die de mug doden.’

  3. [verwijderd] 24 januari 2007 08:25
    Published: 08:13 24.01.2007 GMT+1 /HUGIN /Source: Crucell N.V. /AEX: CRXL /ISIN: NL0000358562

    Crucell awarded EU grant to develop malaria vaccine

    Leiden, The Netherlands, January 24, 2007 - Dutch biotechnology company Crucell N.V. (Euronext, NASDAQ: CRXL; Swiss Exchange: CRX) today announced that it had received a European Union-funded grant aimed at advancing the development of a malaria vaccine. The ¿2.4 million grant, which was awarded to a Crucell-led consortium of six leading European Universities and companies in the field of malaria research, will finance pre-clinical studies toward an affordable, safe and efficacious two-component pediatric malaria vaccine.

    "We are grateful to the EU for its decision to give us this grant," said Dr. Jaap Goudsmit, Crucell's Chief Scientific Officer. "The grant is important to our efforts to develop a malaria vaccine." Dr. Goudsmit added: "The grant will go a long way toward streamlining Crucell's focus on the fundamental global needs for a much-needed malaria vaccine."

    About Malaria
    Malaria is one of the biggest killers among communicable diseases today. It is caused by the Plasmodium parasite and transmitted from person-to-person through the bite of a female Anopheles mosquito. The disease currently represents one of the most prevalent infections in tropical and subtropical areas causing severe illness in 300 to 500 million individuals worldwide and causing up to three million deaths every year. Most of these deaths occur among children and pregnant women in the developing world, especially in sub-Saharan Africa. Although the overwhelming majority of morbidity and mortality associated with malaria occur in the developing world, the disease also affects travelers.

    About Crucell
    Crucell N.V. (Euronext, NASDAQ: CRXL; Swiss Exchange: CRX) is a biotechnology company focused on research, development and worldwide marketing of vaccines and antibodies that prevent and treat infectious diseases. Its vaccines are sold in public and private markets worldwide. Crucell's core portfolio includes a vaccine against hepatitis B, a fully-liquid vaccine against five important childhood diseases, and a virosome-adjuvanted vaccine against influenza. Crucell also markets travel vaccines, such as the only oral anti-typhoid vaccine, an oral cholera vaccine and the only aluminum-free hepatitis A vaccine on the market. The Company has a broad development pipeline, with several Crucell products based on its unique PER.C6® production technology. The Company licenses this and other technologies to the biopharmaceutical industry. Important partners and licensees include DSM Biologics, sanofi aventis, GSK and Merck & Co. Crucell is headquartered in Leiden (the Netherlands), with subsidiaries in Switzerland, Spain, Italy, Sweden, Korea and the US. The Company employs over a 1000 people. For more information, please visit www.crucell.com.

    Forward-looking statements
    This press release contains forward-looking statements that involve inherent risks and uncertainties. We have identified certain important factors that may cause actual results to differ materially from those contained in such forward-looking statements. For information relating to these factors please refer to our Form 20-F, as filed with the U.S. Securities and Exchange Commission on July 6, 2006, and the section entitled "Risk Factors". The Company prepares its financial statements under generally accepted accounting principles in the United States (US GAAP) and Europe (IFRS).

    For further information please contact:
    Crucell N.V.
    Leonard Kruimer
    Chief Financial Officer
    Tel. +31-(0)71-524 8722
    Leonard.Kruimer@crucell.com
    For Crucell in the US:
    Redington, Inc.
    Thomas Redington
    Tel. +1 212-926-1733
    tredington@redingtoninc.com
  4. [verwijderd] 24 januari 2007 08:38
    Crucell krijgt EU-beurs voor ontwikkeling malariamedicijn24 jan 2007, 08:33 uur
    Amsterdam (BETTEN BEURSMEDIA NEWS) - Crucell heeft van de Europese Unie een beurs ontvangen van EUR 2,4 miljoen, voor de verdere ontwikkeling van een malariamedicijn. Dat heeft het Leidse biotechnologiebedrijf woensdag bekendgemaakt.

    Het geldbedrag is toegewezen aan een door Crucell geleid consortium van zes bedrijven met een leidende positie op het gebied van onderzoek naar malaria.

    Malaria staat in de topdrie van meest dodelijke besmettelijke ziektes. Wereldwijd worden in meer dan 500 miljoen gevallen mensen ernstig ziek, waarbij e e n tot drie miljoen mensen jaarlijks sterven. Op dit moment is er geen vaccin op de markt dat bescherming biedt tegen malaria.

    (c) BETTEN BEURSMEDIA NEWS (tel: +31 20 710 1756; fax: +31 20 710 1875)

  5. [verwijderd] 25 januari 2007 06:30
    In het volgende reveiw wordt een mooi overzicht gegeven over alle (bijna alle !) ontwikkelingen in het malaria vaccine.
    Ook al wordt Crucell niet genoemd, de prime-boost strategie krijgt wel aandacht. Het is wel een goede paper om te lezen, ook om te weten wat de concurrentie doet.

    A review of human vaccine research and development: Malaria
    Vaccine Volume 25, Issue 9 , 19 February 2007, Pages 1567-1580

    Marc P. Girarda, Zarifah H. Reedb, Martin Friedeb and Marie Paule Kienyb

    University Paris 7, 39 rue Seignemartin, FR-69008 Lyon, France
    bInitiative for Vaccine Research, World Health Organization, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland

    Abstract

    The last several years have seen significant progress in the development of vaccines against malaria. Most recently, proof-of-concept of vaccine-induced protection from malaria infection and disease was demonstrated in African children. Pursued by various groups and on many fronts, several other candidate vaccines are in early clinical trials. Yet, despite the optimism and promise, an effective malaria vaccine is not yet available, in part because of the lack of understanding of the types of immune responses needed for protection, added to the difficulty of identifying, selecting and producing the appropriate protective antigens from a parasite with a genome of well over five thousand genes and to the frequent need to enhance the immunogenicity of purified antigens through the use of novel adjuvants or delivery systems. Insufficient clinical trial capacity and normative research functions such as local ethical committee reviews also contribute to slow down the development process. This article attempts to summarize the state of the art of malaria vaccine development.

    4. Vaccines

    4.1. General considerations
    As mentioned above, several lines of evidence suggest that a prophylactic malaria vaccine for humans is feasible. Firstly, immunization of naive human volunteers with irradiated (and thus attenuated) sporozoites was shown to confer 90% sterile protection against experimental infection following laboratory-bred, sporozoite-infected mosquito bites [36] and [37]. Secondly, naturally acquired immunity progressively builds up during the first two decades of life in people living in malaria-endemic countries. This immunity primarily impacts the severity of clinical disease, and appears to be linked to continuous antigenic stimulation, waning rapidly when exposure ceases [10], [38] and [39]. Thirdly, protection has been elicited by passive transfer of hyperimmune immunoglobulins from malaria-immune adults into malaria-naïve human volunteers [11].

    Key obstacles to the development of a vaccine include the lack of immune correlates of protection, the lack of reliable and predictive animal models, and the developmental and antigenic variability of the parasite. An additional obstacle has been the paucity of expertise in GMP vaccine development in the non-industrial centers where much of the malaria vaccine research has been undertaken so far, and the lack of vaccine development platforms to develop clinically acceptable adjuvants able to induce cell-mediated immunity as well as epitope- or antigen-presenting systems. Much work has nevertheless been done to determine which protective antigens or epitopes should be used in the construction of recombinant, subunit or synthetic malaria vaccines.

    The traditional approach to develop malaria vaccines has focused on the targeting of one of the different stages of parasite development, whether the pre-erythrocytic, the asexual (intra-erythrocytic) or the sexual stage. Pre-erythrocytic vaccine strategies aim to generate an antibody response able to neutralize sporozoites and prevent them from invading the hepatocyte, as well as to elicit a cell-mediated immune response able to interfere with the intra-hepatic multiplication cycle of the parasites, e.g. by killing the parasite-infected hepatocytes. This type of vaccine would be ideal for travelers because it would prevent the advent of any form of clinical disease. Asexual blood-stage (erythrocytic stage) vaccine strategies aim to elicit antibodies that will inactivate merozoites and/or target malarial antigens expressed on the RBC surface through antibody-dependent cellular cytotoxicity and/or complement lysis; and also are meant to elicit T-cell responses able to inhibit the development of the parasite in RBCs. By decreasing the exponential multiplication of merozoites, this type of vaccine would mostly serve as a disease-reduction vaccine in endemic countries [40]. As for vaccines that target the sexual stage of the parasite, they do not aim to prevent illness or infection in the vaccinated individual, but to prevent or decrease transmission of the parasite to new hosts. This ‘transmission-blocking’ vaccine can be seen as a true altruistic vaccine.

    Besides these classical approaches, novel approaches being currently undertaken include the development of an irradiated sporozoite vaccine [41] and an anti-parasite toxin vaccine that targets the parasite toxins which contribute to the disease, such as the glycosylphosphatidylinositol (GPI) anchor. Recent promising results obtained with knock-out sporozoites in mice will likely lead to further developments over the coming years [21], [42] and [43].

    Uiteindelijk volgt dan een lange opsomming van alle vaccines die gemaakt worden. Helaas wordt Crucell niet genoemd en de papers van Goudsmit's groep worden niet geciteerd.
    Dat is nu jammer.

    Wie de pdf wil hebben kan weer een mail sturen naar biocon60@hotmail.com
  6. [verwijderd] 26 januari 2007 12:19
    Volgens mij is het malaria verhaal aangepast.

    www.crucell.nl/R_and_D-Discovery_Prog...



    Within the international PRIBOMAL consortium, Crucell is participating in pre-clinical studies towards an affordable, safe and efficacious two-component pediatric malaria vaccine. The aim of this project is to demonstrate feasibility (safety and efficacy) in pre-clinical studies of a novel, affordable, two-component, pediatric malaria vaccine.




    Malaria is one of the major public health challenges in the world, causing more than one million deaths each year. The disease affects primarily children of the developing world, and it is understood to be both a disease of poverty and a cause of poverty. The available measures, such as personal protection or drugs, have proven insufficient to control the disease. A safe, affordable and efficacious pediatric malaria vaccine, which fits in the existing WHO Expanded Program on Immunization, would solve tremendous suffering to human kind.




    The vaccine consists of a prime, to be administered at birth, of a novel recombinant BCG vector carrying, preferentially, multiple antigens derived from the Plasmodium falciparum parasite, the cause of malaria. The priming vaccine is followed at week 14 after birth by a booster vaccination using an industrially developed, recombinant adenoviral vector carrying the identical P. falciparum antigens as the rBCG-based malaria vaccine.



    Although no vaccine is available yet, studies using a truncated circumsporozoite (CS) protein of P. falciparum directly fused to the hepatitis B surface antigen, named RTS,S, has shown excellent safety and provided approximately 30-40% protection in human field trials in Africa. Such studies are extremely important because they demonstrate the feasibility of effective vaccination against P. falciparum, although RTS,S induced only limited memory T-cell responses and consequently the immune response lasted only for a short period.



    It is now generally accepted that immunological control of P. falciparum will require a vaccine that induces both high level neutralizing antibodies as well as strong T-cell response. Hereto, many different technologies are currently being explored including vaccines based on synthetic peptides/proteins, recombinant DNA, recombinant viral vectors, and attenuated bacterial vectors.



    Among all the technologies currently under development there are two systems, i.e. recombinant BCG (rBCG) and recombinant adenovirus (rAd), that stand out from the rest, based on their ability to elicit strong antigen-specific humoral and cellular host responses, and the availability of efficient production systems able to provide sufficient vaccine dosages for hundreds of millions in need. Crucell’s AdVac® technology is currently being evaluated against, amongst others, poverty-related diseases malaria, tuberculosis and HIV. The two vaccine components will be assembled according to the latest developments in industrial and academic vaccine technology, which are considered as state of the art.



    The ultimate deliverable of this program is an efficacious pediatric malaria vaccine candidate that will eventually be advanced to GMP development and human clinical trials. Besides reaching this aim, the consortium expects that during the execution of this program an extensive knowledge will be gathered regarding immunological features of different vaccination schedules, in combination with information on their protective ability.


    Malaria is one of today’s top three killers among communicable diseases. The disease currently represents one of the most prevalent infections in tropical and subtropical areas causing severe illness in 300 to 500 million individuals worldwide and causing one to three million deaths every year. Most of these deaths occur among children and pregnant women in the developing world, especially in sub-Saharan Africa. Unfortunately, mortality associated with severe or complicated malaria still exceeds 10-30%. Malaria is caused by the Plasmodium parasite and transmitted from person-to-person through the bite of a female Anopheles mosquito. Although the overwhelming majority of morbidity and mortality associated with malaria occur in the developing world, this disease also affects travelers.

  7. [verwijderd] 26 januari 2007 12:30
    quote:

    wpw schreef:

    Volgens mij is het malaria verhaal aangepast.

    www.crucell.nl/R_and_D-Discovery_Prog...

    Zoek de verschillen.....

    Pagina, d.d. 08-09-2006:
    Pediatric Malaria Vaccine

    Description
    Within the international PRIBOMAL consortium, Crucell is participating in pre-clinical studies towards an affordable, safe and efficacious two-component pediatric malaria vaccine. The aim of this project is to demonstrate feasibility (safety and efficacy) in pre-clinical studies of a novel, affordable, two-component, pediatric malaria vaccine.

    Development Rationale
    Malaria is one of the major public health challenges in the world, causing more than one million deaths each year. The disease affects primarily children of the developing world, and it is understood to be both a disease of poverty and a cause of poverty. The available measures, such as personal protection or drugs, have proven insufficient to control the disease. A safe, affordable and efficacious pediatric malaria vaccine, which fits in the existing WHO Expanded Program on Immunization, would solve tremendous suffering to human kind.

    Development Status
    The vaccine consists of a prime, to be administered at birth, of a novel recombinant BCG vector carrying, preferentially, multiple antigens derived from the Plasmodium falciparum parasite, the cause of malaria. The priming vaccine is followed at week 14 after birth by a booster vaccination using an industrially developed, recombinant adenoviral vector carrying the identical P. falciparum antigens as the rBCG-based malaria vaccine.
    Although no vaccine is available yet, studies using a truncated circumsporozoite (CS) protein of P. falciparum directly fused to the hepatitis B surface antigen, named RTS,S, has shown excellent safety and provided approximately 30-40% protection in human field trials in Africa. Such studies are extremely important because they demonstrate the feasibility of effective vaccination against P. falciparum, although RTS,S induced only limited memory T-cell responses and consequently the immune response lasted only for a short period.
    It is now generally accepted that immunological control of P. falciparum will require a vaccine that induces both high level neutralizing antibodies as well as strong T-cell response. Hereto, many different technologies are currently being explored including vaccines based on synthetic peptides/proteins, recombinant DNA, recombinant viral vectors, and attenuated bacterial vectors.
    Among all the technologies currently under development there are two systems, i.e. recombinant BCG (rBCG) and recombinant adenovirus (rAd), that stand out from the rest, based on their ability to elicit strong antigen-specific humoral and cellular host responses, and the availability of efficient production systems able to provide sufficient vaccine dosages for hundreds of millions in need. Crucell’s AdVac® technology is currently being evaluated against, amongst others, poverty-related diseases malaria, tuberculosis and HIV. The two vaccine components will be assembled according to the latest developments in industrial and academic vaccine technology, which are considered as state of the art.
    The ultimate deliverable of this program is an efficacious pediatric malaria vaccine candidate that will eventually be advanced to GMP development and human clinical trials. Besides reaching this aim, the consortium expects that during the execution of this program an extensive knowledge will be gathered regarding immunological features of different vaccination schedules, in combination with information on their protective ability.

    About malaria
    Malaria is one of today’s top three killers among communicable diseases. The disease currently represents one of the most prevalent infections in tropical and subtropical areas causing severe illness in 300 to 500 million individuals worldwide and causing one to three million deaths every year. Most of these deaths occur among children and pregnant women in the developing world, especially in sub-Saharan Africa. Unfortunately, mortality associated with severe or complicated malaria still exceeds 10-30%. Malaria is caused by the Plasmodium parasite and transmitted from person-to-person through the bite of a female Anopheles mosquito. Although the overwhelming majority of morbidity and mortality associated with malaria occur in the developing world, this disease also affects travelers.

    www.iex.nl/forum/topic.asp?forum=228&...
  8. [verwijderd] 29 januari 2007 15:08
    EU researchers to develop malaria vaccine
    [Date: 2007-01-26]

    A network of European researchers has been awarded EUR 2.4 million by the EU to take forward research into a malaria vaccine. Currently there is no licensed vaccine for the disease, although there are a number of potential vaccines at various stages of development.

    The project is called 'Preclinical Studies towards an affordable, safe and efficacious two component paediatric malaria vaccine'. Coordinated by Dutch biotechnology company Crucell, the project will run for three years.

    The project partners plan to carry out pre-clinical trials of a vaccine in which a version of the BCG (tuberculosis) vaccine is used as a vector for the malaria antigen. The BCG is already given to children at birth as part of the vaccination schedule in Africa, so combining the two makes a lot of sense, say the researchers.

    During the project, the partners will carry out studies on animals to investigate how well the vaccine works and determine the best dose.

    Crucell is also working on another approach to the malaria vaccine problem, which involves inserting parts of the malaria parasite into a virus that carries the vaccine into the body. This approach, which has been developed in partnership with the US' National Institutes of Health, is at a much later stage of development, having reached the clinical trials stage.

    Malaria is caused by a parasite called Plasmodium, which is transmitted to humans by Anopheles mosquitoes. Symptoms include fever, headache and vomiting. According to figures from the World Health Organisation, malaria causes more than 300 million acute illnesses and at least one million deaths every year. Most of these deaths are young children living in sub-Saharan Africa.

    Over the years the malaria parasite has increasingly developed resistance to drugs developed to combat it, while the Anopheles mosquito has become resistant to many insecticides, making the search for a vaccine to prevent the disease ever more important.
    cordis.europa.eu/fetch?CALLER=EN_NEWS...
  9. gogogoo 1 februari 2007 11:46
    Democrats Propose $463.5B Spending Bill; Allocate $1.3B Increase To Fund International HIV/AIDS, TB, Malaria Programs
    Main Category: HIV / AIDS News
    Article Date: 01 Feb 2007 - 1:00 PST
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    Congressional Democrats on Monday released a $463.5 billion spending resolution (HJ Res 20) for fiscal year 2007 that includes a $1.3 billion increase for international HIV/AIDS, tuberculosis and malaria programs, bringing the total for the President's Emergency Plan for AIDS Relief to $4.5 billion, the AP/Houston Chronicle reports (Taylor, AP/Houston Chronicle, 1/30). PEPFAR is a five-year, $15 billion program that directs funding for HIV/AIDS, tuberculosis and malaria primarily to 15 focus countries and provides funding to the Global Fund To Fight AIDS, Tuberculosis and Malaria (Kaiser Daily HIV/AIDS Report, 1/12). The $4.5 billion for PEPFAR includes $3.2 billion for the State Department's Global HIV/AIDS Initiative, $712 million for USAID's Child Survival and Health Program, and $494 million for CDC and HHS global HIV/AIDS activities, according to a House Appropriations Committee summary. Of these amounts, $724 million would be allocated for the U.S. contribution to the Global Fund, with $625 million coming from the State Department and USAID, and $99 million from HHS. In addition, $248 million would be allocated to expand programs under the President's Malaria Initiative, an increase of $149 million. The resolution also allocates an additional $75.8 million in funding for the Ryan White CARE Act , which provides care and services to people living with HIV/AIDS in the U.S., to bring its funding to $1.2 billion (House Appropriations Committee summary, 1/29). However, the resolution does not appear to grant Bush's request to increase funding for the Millennium Challenge Corporation, a program meant to encourage economic and political reforms in developing countries, the AP/CBS News reports. According to the AP/CBS news, the resolution would freeze most other federal spending at 2006 levels (Taylor, AP/CBS News, 1/30). "I don't expect people to love this proposal, I don't love this proposal, and we probably have made some wrong choices," House Appropriations Committee Chair David Obey (D-Wis.) said, adding, "At least we have made them in order to bring last year's issues to a conclusion so we can turn the page and deal with next year's priorities." The bill is scheduled for a House vote on Wednesday, the AP/Chronicle reports (AP/Houston Chronicle, 1/30).

    www.medicalnewstoday.com/medicalnews....
  10. [verwijderd] 1 februari 2007 11:56
    quote:

    gogogoo schreef:

    Congressional Democrats on Monday released a $463.5 billion spending resolution (HJ Res 20) for fiscal year 2007 that includes a $1.3 billion increase for international HIV/AIDS, tuberculosis and malaria programs, bringing the total for the President's Emergency Plan for AIDS Relief to $4.5 billion, the AP/Houston Chronicle reports (Taylor, AP/Houston Chronicle, 1/30). PEPFAR is a five-year, $15 billion program that directs funding for HIV/AIDS, tuberculosis and malaria primarily to 15 focus countries and provides funding to the Global Fund To Fight AIDS, Tuberculosis and Malaria (Kaiser Daily HIV/AIDS Report, 1/12). The $4.5 billion for PEPFAR includes $3.2 billion for the State Department's Global HIV/AIDS Initiative, $712 million for USAID's Child Survival and Health Program, and $494 million for CDC and HHS global HIV/AIDS activities, according to a House Appropriations Committee summary. Of these amounts, $724 million would be allocated for the U.S. contribution to the Global Fund, with $625 million coming from the State Department and USAID, and $99 million from HHS. In addition, $248 million would be allocated to expand programs under the President's Malaria Initiative, an increase of $149 million.
    Zie ook:
    www.iex.nl/forum/topic.asp?forum=228&...
    kaisernetwork.org/daily_reports/rep_i...
    thomas.loc.gov/cgi-bin/query/z?c110:H...
  11. [verwijderd] 13 februari 2007 19:17
    More Than 4.3 Million Malaria Medicines Tested Thanks To Calculation Grids
    Main Category: Tropical Diseases News
    Article Date: 13 Feb 2007 - 9:00 PST


    The second phase of the Wisdom experiment, carried out as an international cooperation project involving IN2P3 /CNRS, was completed on January 31. Thanks to the association of several international calculation grids , including the European grid Egee , it was possible to analyze close to 80,000 potential medicines for the treatment of malaria per hour over the course of 10 weeks. Wisdom opened up new therapeutic possibilities for the treatment of this illness and also for the fight against other tropical diseases.

    Wisdom's strategy is based on a virtual screening of molecules with encouraging therapeutic performances: it allows researchers to calculate the probability that a molecule (called an active molecule or "ligand") will bind to a target protein, thereby altering its biological activity, and, in the case of malaria, the proliferation of the parasite. Over the ten weeks of the experiment, 4.3 million active molecules (potential medicines) were tested, and more than 140 million linkages between these molecules and the target proteins to combat malaria were calculated. Through this process, it was possible to reject a large number of compounds in record time, allowing researchers to focus the biological tests on the most promising chemical compounds. While accelerating the process of selection of the "best" molecules, this strategy can also substantially reduce the cost of developing new medicines against this disease which has an especially large impact on developing countries.

    The impact of the approach used in Wisdom goes beyond malaria. This strategy can be extended to all diseases, opening up major possibilities for industry. Furthermore, Wisdom allows for a systematic investigation of all potentially valuable compounds whereas, until now, the search for new medicines in the academic sector was carried out on a small scale.

    In 2005, the first large-scale deployment on the Egee grid screened more than 41 million chemical compounds in only six weeks, representing the equivalent of 80 years of calculations on a standard computer. Of the 5,000 best chemical compounds selected in this screening, three families of molecules in particular caught the attention of the researchers: two were already known for their action on the targeted protein while the third is completely new. Analysis of the most promising compounds is continuing at the University of Modena in Italy and at the Laboratoire de physique corpusculaire (LPC) in Clermont-Ferrand (IN2P3/CNRS, Blaise Pascal University) before being sent for in vitro tests at the enzymology laboratory of Chonnam National University (South Korea).

    AN INTERNATIONAL MOBILIZATION

    The success of this first initiative attracted the interest of the international research community, which led to a deployment for avian influenza in April and May 2006 and then this second deployment for malaria for new target proteins proposed by French, Italian, Venezuelan and South African laboratories. Many calculation grids joined this effort: the regional grid Auvergrid in Auvergne, the EELA, EUChinaGRID, EUMedGRID and ASGC TWGrid grids made their calculation resources available, supplementing those of the Egee grid. Lastly, two other European projects, Embrace and BioinfoGRID, are contributing to improving the selection of the most promising molecules from among the millions of commercially-available chemical compounds.

    For this second phase of the Wisdom project, more than 5,000 computers were mobilized simultaneously in 27 countries, producing more than 2,000 gigabits of data, which represents the equivalent of 413 years of calculations on a single computer. In France, several CNRS laboratories made a very significant contribution: the Calculation Center of IN2P3 manages the resources made available for this initiative and the LPC supervises the use of the resources for the various scientific calculations. The contribution of all of the French laboratories on the Egee grid represents about 15% of the 413 years of calculations.

    ###

    CONTACTS

    Researcher Contact: Vincent Breton

  12. [verwijderd] 14 februari 2008 14:10
    12-02-2008
    AdVac®/PER.C6® Technology-Based Malaria Vaccine: Crucell and its partner, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), are conducting a Phase I trial in the U.S. The study is being carried out on two sites, VanderBilt and Stanford University. The first and second cohorts, comprising 18 and 17 volunteers respectively, have been successfully enrolled. No serious adverse side-effects have been reported to date. Current plans call for subsequent enrollment of two additional cohorts at higher vaccine doses, provided the vaccine has an appropriate safety profile. Following review of the safety data by a Safety Monitoring Committee, a decision has been made to begin recruitment of the third cohort. Initial findings of this Phase I trial are expected to be available in 2008.

    nov 28, 2007 21:29
    Naast Vanderbilt University, Nashville, Tennessee en Stanford University, Stanford, California, nu ook een clinical site in Montana.
    crucell.yourbb.nl/viewtopic.php?f=5&t...

    clinicaltrials.gov/ct2/show/NCT003711...

    www.iex.nl/forum/topic.asp?forum=228&...
    www.iex.nl/forum/topic.asp?forum=228&...
    www.iex.nl/forum/topic.asp?forum=228&...

    Meer…. crucell.yourbb.nl/viewtopic.php?f=7&t...
  13. flosz 1 maart 2008 09:47
    Art. Nature:
    ...Heppner, for example, says that results of studies he and his colleagues have carried out on macaques indicate that combining an adenovirus-based vaccine made by the Netherlands biotech company CruCell with RTS,S would offer much better effects.....

    Published online 27 February 2008 | Nature 451, 1042-1046 (2008) | doi:10.1038/4511042a

    Malaria: The end of the beginning
    After decades of work, a pioneering malaria vaccine may soon reach the final phase of clinical trials. In the first of two features on efforts against malaria, Brendan Maher reports on a vaccine that is far from perfect - but which may provide new direction and save thousands of lives.
    Brendan Maher
    In 1987 Rip Ballou taped an ice-cream carton to his arm. The young US Army doctor was doing his bit for science; inside the carton five hungry mosquitoes set about doing theirs. It's an uncomfortable situation, Ballou remembers with a grimace, to have a bunch of the insects “just whaling away on your arm”; all the more so when you know that they have been carefully infected with malaria parasites, and soon you will be too.
    Ballou and five colleagues at Walter Reed Army Institute of Research (WRAIR) in Silver Spring Maryland were testing a vaccine candidate, FSV-1. They'd first been injected with it a year earlier; now it was time for any immunity they might have developed as a result to be 'challenged'. Nine days after the mosquitoes had their meals, the first unvaccinated control tested positive for parasites and was given drugs to clear his system. The second control and three vaccinated volunteers followed suit in short order, apparently no more resistant.
    On the eleventh day another of the six volunteers fell ill — the tremors struck Stephen Hoffman, a WRAIR colleague in the Navy as he was giving a lecture in San Diego. On the twelfth day, while at a party, Ballou started to feel out of sorts. Not sure if it was the home-brewed beer he'd been drinking or parasites ravaging his red blood cells, he had his wife drive home. Soon he was cycling between chills and fevers and experiencing headaches of unprecedented intensity. “I have never been so sick in my life,” he says. “It gave me an extremely healthy respect for this disease.” Five of them had succumbed.
    But the sixth vaccinee, Daniel Gordon, was still healthy more than four weeks later. For the first time a simple vaccine had protected someone from malaria1.
    That first glimmer of hope grew into an extensive collaboration between WRAIR and the drug company GlaxoSmithKline (GSK) that has turned a descendant of the FSV-1 vaccine, the oddly named RTS,S, into the world's 'most advanced' malaria vaccine. Most advanced means that phase III clinical trials, the final step before licensing the drug, could start by this September. If they go well the vaccine could be licensed and in use by 2011.
    To get this far speaks of determination, imagination and perseverance — qualities Ballou and his colleagues, like so many researchers into tropical medicine, show in abundance. It also speaks of something rarer in the field: a lot of money. All told, GSK and partners will have spent upwards of US$500 million by the end of the next set of trials. “We were convinced that if we develop the malaria vaccine it will be hard for society to refuse to pay for it,” explains Jean Stéphenne, president and general manager of GSK Biologicals, the unit that works on the vaccine at its facility in Rixensart, Belgium.
    And in recent years this conviction has begun to look warranted. Private donors and governments are funnelling hundreds of millions of dollars into projects such as the GAVI Alliance, which provides access to immunizations in the developing world; there is increasing pressure for countries to promise 'advanced market commitment', the setting aside of funds today to buy vaccines when they become available tomorrow.
    But if RTS,S is the first vaccine to be so bought, it will still fall short of the traditional goals for vaccines. It has improved since its meagre one-in-six showing in that first 1987 challenge, but not that much. RTS,S will offer at best partial protection, maybe 30%, against infection; some indicators predict it might diminish levels of severe malaria by as much as 50%. That may be enough to give infants and small children a better chance of surviving the scourge while they're most vulnerable. But it is a long way from the last word.

    Hill's doubts about the vaccine bolster a more general frustration with what he sees as GSK's go-it-alone approach, “unconnected to the other 12 or 15 groups developing vaccines” (see table 1). He and others want different vaccines to be combined with RTS,S in Phase II testing, suspecting efficacy might be greatly enhanced. Heppner, for example, says that results of studies he and his colleagues have carried out on macaques indicate that combining an adenovirus-based vaccine made by the Netherlands biotech company CruCell with RTS,S would offer much better effects[10]: “My hope is that a way can be found to evaluate this clinically just as we've done for earlier improvements of RTS,S.” Ballou says that although progress in studying this combination has been stalled for “various business reasons”, several collaborative efforts continue.

    Volledig art. via:
    crucell.yourbb.nl/viewtopic.php?f=7&t...
  14. flosz 1 maart 2008 10:16
    DEVELOPING A MALARIA VACCINE FEBRUARY 2008

    Currently there is no effective vaccine to protect against infection with the Plasmodium falciparum parasite, which causes a great number of cases of malaria. Various treatments are available but due to the worsening problems of drug resistance in many parts of the world, adequate treatment of malaria is becoming increasingly difficult. In addition, many insecticides are no longer useful against mosquitoes transmitting the disease.
    To develop an effective and safe malaria vaccine, Crucell formed collaborative development programs involving three leading malaria research organizations: New York University (NYU), GlaxoSmithKline Biologicals (GSK), and Walter Reed Army Institute of Research (WRAIR). Crucell's collaboration with NYU yielded favorable results demonstrating that Crucell’s candidate malaria vaccine protected mice against infection with a mouse parasite equivalent to that of the human parasite causing malaria. In a second collaboration, Crucell entered into a Cooperative Research and Development Agreement (CRADA) with WRAIR and GSK to evaluate Crucell's candidate malaria vaccine directed against the human malaria parasite, Plasmodium falciparum. In line with this agreement, Crucell's candidate vaccine was tested in pre-clinical studies as a stand-alone vaccine and in combination with GSK’s malaria vaccine candidate, called RTS,S. These studies have shown that Crucell’s AdVac® vaccine candidate efficiently primed and/or boosted malaria specific immune responses.
    The GSK candidate malaria vaccine, RTS,S, has been shown to confer partial protection to human volunteers in both a laboratory challenge model conducted at WRAIR and under natural challenge conditions in a field study conducted in Gambia. In studies published in the Lancet in 2004 and 2007, results from Phase IIb pediatric trials in Mozambique showed further promising results, with the vaccine protecting some infants against infection and making the course of the disease less serious and life threatening in others.
    In March 2004, the National Institutes of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH) agreed to support the development of Crucell's candidate malaria vaccine. The agreement has an estimated value of up to US$ 3.5 million and covers process development costs of the candidate vaccine including manufacturing of clinical trial material and Investigational New Drug (IND) filing. The work is being carried out under a subcontract agreement with Science Applications International Corporation (SAIC).
    In partnership with the NIAID, Crucell’s malaria vaccine entered a Phase I trial in the US in Q4 2006. The study is being carried out on two sites, VanderBilt and Stanford University. The first and second cohorts, comprising 18 and 17 volunteers respectively, have been successfully enrolled. No serious adverse side effects have been reported to date. Current plans call for subsequent enrollment of two additional cohorts at higher vaccine doses, provided the vaccine has an appropriate safety profile. Following review of the safety data by a Safety Monitoring Committee, a decision has been made to begin recruitment of the third cohort. Initial findings of this Phase I trial are expected to be available in 2008.
    Malaria Vaccine Production Process
    Crucell’s candidate malaria vaccine is based on Crucell’s AdVac® technology. It is made by inserting selected parts of the malaria parasite into an adenoviral vector, which acts as a ‘vehicle’ for vaccination delivery. AdVac® technology uses adenoviral vectors that do not regularly occur in the human population. In this case, the vector is based on adenovirus serotype 35 (Ad35).
    The AdVac® vector carrying the malaria gene cannot “replicate independently” – it is replication incompetent. Replication of the vector can only occur in PER.C6® cells. Once the vector carrying the malaria gene is inoculated into PER.C6® cells, large quantities of the vector are produced, making commercial-scale manufacturing of the vaccine possible. The resulting product then undergoes extensive purification before use as a vaccine.
    This vaccination method provides a very important safety advantage, while ensuring that a strong immune response is elicited against the malaria parasite. The steps used in producing such a vaccine are outlined in a simplified form in the following diagram.

    About PER.C6® Technology
    Crucell's PER.C6® human cell line technology is ideally suited for the development and large-scale manufacturing of a wide range of biopharmaceuticals including vaccines, antibodies, therapeutic proteins and gene therapy products. Many of today's vaccines are produced on animal-derived substrates, including fertilized chicken eggs and mouse brains. To overcome limitations in production capacity, processing time, and potential safety risks associated with the use of animal derived substrates, Crucell's PER.C6® technology is an attractive alternative production technology for the manufacturing of inactivated whole virus, live-attenuated, live-vector and subunit vaccines. PER.C6® technology supports the growth of a wide variety of human disease-causing viruses that can subsequently be processed into vaccines suitable for administration to humans. Many viruses have been demonstrated to efficiently replicate on PER.C6® cells. In addition, Crucell's PER.C6® technology allows for efficient production of recombinant vaccines.

    About AdVac®
    AdVac® technology supports the practice of inserting genetic material from a disease-causing virus or parasite into a ‘vehicle’ called a vector, which then delivers the immunogenic material directly to the immune system. Currently, the most commonly used recombinant vaccine vector is based on adenovirus serotype 5 (Ad5), a virus that causes the common cold. However, antibodies to Ad5 are widespread among people of all ages and are known to lower the immune response to recombinant Ad5-based vaccines, thereby impairing the efficacy of these vaccines. The AdVac® technology is specifically designed to manage the problem of pre-existing immunity in humans against Ad5, without compromising large-scale production capabilities or the immunogenic properties of Ad5. AdVac® technology is based on adenovirus vectors that do not regularly occur in the human population, such as adenovirus serotypes 11 and 35. In view of the prevalent pre-existing immunity to Ad5 in humans, AdVac® vectors may potentially be more effective vaccine vectors. All of Crucell’s vaccine candidates based on AdVac® are produced using Crucell’s PER.C6® production technology.
    www.crucell.com/page/downloads/Factsh...
  15. flosz 1 maart 2008 10:17
    ABOUT MALARIA FEBRUARY 2008

    Malaria is a life-threatening parasitic disease transmitted by mosquitoes. It is estimated that malaria started having an impact on human survival about 10,000 years ago. Malaria spread during the following centuries throughout the world and is thought to have been introduced to the New World from Europe and Africa during the sixteenth century. It was once believed that the disease came from fetid marshes, hence the Latin name “mal aria”, (meaning bad air). In 1880, however, scientists discovered the true cause of malaria is a one-cell parasite called Plasmodium. Later they discovered that the parasite was transmitted from person to person through the bite of a female Anopheles mosquito.
    Morbidity and Mortality
    Malaria is one of the top three killers among communicable diseases. Together with HIV/AIDS and TB, malaria is one of the major public health challenges undermining development in the poorest countries in the world. In fact, malaria currently represents one of the most prevalent infections in tropical and subtropical areas, causing severe illness in up to 500 million people worldwide each year and causing up to three million deaths. Most of these deaths occur among children and pregnant women in the developing world, especially in sub-Saharan Africa. Unfortunately, mortality associated with severe or complicated malaria still exceeds 10-30%. Although the overwhelming majority of morbidity and mortality associated with malaria occur in the developing world, this disease also affects travelers. Each year, approximately 30,000 individuals traveling from industrialized nations to the developing world contract malaria.
    Geographical Distribution
    Currently, approximately 40% of the world’s population, mostly those living in tropical and subtropical regions, is at risk of contracting malaria. The widespread occurrence and elevated incidence of malaria are a consequence of discontinued malaria control programs, the increasing numbers of drug-resistant parasites, and insecticide-resistant mosquitoes. Other factors include environmental and climatic changes, civil disturbances, and increased mobility of populations. There are four Plasmodium species that cause malaria and these are found in regions all around the world. The Anopheles mosquito occurs in most areas of the globe with around 40 species important to the spread of malaria.
    Transmission
    Malaria parasites are transmitted to humans by the bite of female Anopheles mosquitoes. Infected mosquitoes inject the malaria parasites into the bloodstream, where they remain for a few minutes before invading the liver cells. Once in the liver, the parasites replicate and develop for about one week until released into the bloodstream. The parasites then invade red blood cells, where they undergo several stages of replication and development before invading new red blood cells. When susceptible mosquitoes ingest infected blood, the parasite completes its maturation inside the insect's gut, finally migrating to the mosquito’s salivary glands. The malaria life cycle is perpetuated when the infected mosquito bites a new human host.
    Symptoms
    Malarial symptoms appear about 9-14 days after the bite of an infected mosquito, although this varies with different Plasmodium species. Typically, the symptoms of infection are flu-like and include chills, fever, and sweating, accompanied by headache, nausea, and vomiting. Life-threatening illnesses associated with severe anemia, impaired consciousness, coma, seizures (cerebral malaria), renal failure, and shock may occur in some infected individuals.
    Treatment and Prevention
    Malaria can be prevented through interventions that minimize the number of mosquitoes as well as effective chemotherapeutic agents, such as chloroquine and mefloquine. However, the use of drugs to prevent malaria remains impractical in the majority of the developing world. Furthermore, the number of drug-resistant parasites and insecticide-resistant mosquitoes is increasing.
    Despite earlier promising results in the 1960’s with prototype vaccines, there is no effective vaccine against malaria available today.
    www.crucell.com/page/downloads/Factsh...
  16. flosz 1 maart 2008 11:24
    En nog even plakken natuurlijk:
    Impact of recombinant Ad35 priming versus boosting of a Plasmodium falciparum protein: characterization of T- and B-cell responses to the liver stage antigen 1 (LSA-1).

    Rodríguez A, Goudsmit J, Companjen A, Mintardjo R, Gillissen G, Tax D, Sijtsma J, Weverling GJ, Holterman L, Lanar DE, Havenga MJ, Radosevic K.
    Crucell Holland BV, PO Box 2048, 2301 CA Leiden, the Netherlands; Center of Poverty-related Communicable Diseases Academic Medical Center, Amsterdam, The Netherlands; Divison of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500.

    Prime-boost vaccination regimens with heterologous antigen delivery systems have indicated that redirection of the immune response is feasible. We showed earlier that T-cell responses to circumsporozoite protein improved significantly when the protein is primed with rAd35.CS. The current study was designed to answer the question whether such an effect can be extended to liver stage antigens of Plasmodium falciparum like LSA-1. Studies in mice have demonstrated that the LSA-1 protein induces strong antibody response but a weak T-cell immunity. We first identified T-cell epitopes in LSA-1 using intracellular IFN-gamma staining, and confirmed these epitopes by means of ELISPOT and pentamer staining. We show that a single immunization with rAd35.LSA-1 induced a strong antigen-specific IFN-gamma CD8(+) T-cell response, but no measurable antibody response. In contrast, vaccinations with the adjuvanted recombinant LSA-1 protein induced remarkably low cellular responses but strong antibody responses. Finally, both priming and boosting of the adjuvanted protein by the rAd35 resulted in enhanced T-cell responses without impairing the level of antibody responses induced by the protein immunizations alone. Furthermore, the incorporation of rAd35 in the vaccination schedule led to a skewing of LSA-1 specific antibody responses towards a Th1 type immune response. Our results show the ability of recombinant Ad35 to induce potent T-cell immunity in combination with protein in a prime-boost schedule, without impairing the B-cell response.
    PMID: 18212075
    www.ncbi.nlm.nih.gov/pubmed/18212075?...

    Linkje art. AMC-magazine:
    Malaria-eiwit binnensmokkelen [februari 2008]
    www.amc.nl/index.cfm?sid=227&uitgavei...
    www.iex.nl/forum/topic.asp?forum=228&...
  17. flosz 1 maart 2008 11:32
    quote:

    flosz schreef:

    Hill's doubts about the vaccine bolster a more general frustration with what he sees as GSK's go-it-alone approach, “unconnected to the other 12 or 15 groups developing vaccines” (see table 1). He and others want different vaccines to be combined with RTS,S in Phase II testing, suspecting efficacy might be greatly enhanced. Heppner, for example, says that results of studies he and his colleagues have carried out on macaques indicate that combining an adenovirus-based vaccine made by the Netherlands biotech company CruCell with RTS,S would offer much better effects[10]: “My hope is that a way can be found to evaluate this clinically just as we've done for earlier improvements of RTS,S.” Ballou says that although progress in studying this combination has been stalled for “various business reasons”, several collaborative efforts continue.

    Tsja... Crucell en GSK...Gentleman's group hug…en dan de zweep erover! Hoogste tijd.
  18. flosz 1 maart 2008 16:31
    nog maar eens een keertje dan......!

    Candidate malaria vaccines in Pre-clinical development
    November 2007

    CSP Adenovirus 35 (WRAIR/Crucell Holland)
    LSA-1 Adenovirus vectored (LSA-NRC) X X
    (WRAIR/Crucell Holland)
    BCG/rAd35 prime-boost CSP/STARP/LSA1(Crucell Holland)
    MSP-1 19 MeV /Crucell/Holland)
    AMA-1 19 MeV (Crucell/Holland) www.who.int/vaccine_research/document...

    crucell.yourbb.nl/viewtopic.php?f=7&t...
    www.iex.nl/forum/topic.asp?forum=228&...
    Geen zin om de overige linkjes op te snorren....
  19. [verwijderd] 1 maart 2008 16:48
    quote:

    flosz schreef:

    [quote=flosz]
    Hill's doubts about the vaccine bolster a more general frustration with what he sees as GSK's go-it-alone approach, “unconnected to the other 12 or 15 groups developing vaccines” (see table 1). He and others want different vaccines to be combined with RTS,S in Phase II testing, suspecting efficacy might be greatly enhanced. Heppner, for example, says that results of studies he and his colleagues have carried out on macaques indicate that combining an adenovirus-based vaccine made by the Netherlands biotech company CruCell with RTS,S would offer much better effects[10]: “My hope is that a way can be found to evaluate this clinically just as we've done for earlier improvements of RTS,S.” Ballou says that although progress in studying this combination has been stalled for “various business reasons”, several collaborative efforts continue.

    [/quote]
    Tsja... Crucell en GSK...Gentleman's group hug…en dan de zweep erover! Hoogste tijd.
    Zou mooie samenwerking zijn.
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