DeBeurs.nl

[verwijderd] 3 oktober 2006 08:52

0

quote:
flosz schreef:
...
Efficacy of RTS,S/AS01 Vaccine Against Episodes of Malaria Due to P. Falciparum Infection in Children.

This study is not yet open for patient recruitment.
Verified by GlaxoSmithKline September 2006

Sponsors and Collaborators: GlaxoSmithKline
...
[/quote]

Dit is (volgens de link) een fase II studie van het GSK vaccin gebaseerd op het RTS,S eiwit, gecombineerd met de AS01 adjuvant, die de immuunrespons drastisch op zou moeten krikken. Dit is dus niet de gecombineerde GSK/Crucell trial.

Die andere door Flosz gequote trial ook niet, die is 'slechts' op basis van adenovirus (waarbij Crucell er niet expliciet bijstaat).

Ik vond nog wel een interessant stukje over de RTS,S/AS01 combinatie, in het jaarverslag over kalenderjaar 2005 van de (mondvol)U.S. Army Medical Materiel Development Activity (USAMMDA) Dit stuk zal dus ergens uit het voorjaar 2006 stammen:

www.usammda.army.mil/HistoricalReport...

[quote= USAMMDA]
Malaria Recombinant Vaccine With Adjuvant Combinations (RTS,S) The RTS,S malaria vaccine, is being developed in collaboration with GlaxoSmithKline Biologicals, to protect U.S. Forces from falciparum malaria. RTS,S vaccine consists of recombinantly engineered immunogenic fractions of the malaria sporozoite surface coat co-expressed with protective epitopes from the hepatitis B surface antigen. During purification, these proteins self-assemble into particles that form the antigenic component of the vaccine. The vaccine, delivered by intramuscular injection, is formulated in a liquid emulsion containing potent immunostimulants (designated as AS02A) that dramatically enhance the immune response to the RTS,S particles. Lead laboratory is WRAIR. In an effort to enhance the immunogenicity and duration of protection, the RTS,S vaccine is being tested in combination with a new, proprietary adjuvant system (AS01B) and evaluated in a Phase 1/2a safety, immunogenicity and preliminary efficacy trial in U.S. volunteers. The study was completed at the WRAIR Clinical Trials Center in CY2005.

(nu komt het interessante stuk - maxen)

Results from this and previous trials indicate that the RTS,S/AS01 vaccine alone will not induce the immunity required for protection of U.S. Forces. Therefore, the strategy has been shifted to examining the use of the RTS,S vaccine in a Prime-Boost combination with an adenovirus vectored malaria vaccine. Studies for the Prime-Boost vaccine will be initiated in late CY2006 and will determine the future direction for this approach.

Dus volgens de US army werkt RTS,S/AS01 niet goed genoeg voor hen, en komt er nog wel degelijk een onderzoek naar een prime-boost met zowel GSK's RTS,S en (Crucell's?) adenovirus. En wel dit jaar nog. Ze zullen nog wel niet bedoelen dat er dit jaar phase I trials beginnen, maar toch. Het is mij overigens niet duidelijk hoe de beleidsvoornemens van de US army zich verhouden tot de onderhandelingen tussen GSK en Crucell...

En blijkbaar ziet GSK het nog zitten met RTS,S/AS01 alleen, anders zouden ze niet een nieuwe (phase II) trial opzetten. Waarschijnlijk is er, met mindere bescherming dan die de US army nastreeft, toch nog vooruitgang te boeken in Afrika...

[verwijderd] 3 oktober 2006 09:26

0

quote:
maxen schreef:
[quote=flosz]
...
Efficacy of RTS,S/AS01 Vaccine Against Episodes of Malaria Due to P. Falciparum Infection in Children.

This study is not yet open for patient recruitment.
Verified by GlaxoSmithKline September 2006

Sponsors and Collaborators: GlaxoSmithKline
...
[/quote]

Dit is (volgens de link) een fase II studie van het GSK vaccin gebaseerd op het RTS,S eiwit, gecombineerd met de AS01 adjuvant, die de immuunrespons drastisch op zou moeten krikken. Dit is dus niet de gecombineerde GSK/Crucell trial.

Die andere door Flosz gequote trial ook niet, die is 'slechts' op basis van adenovirus (waarbij Crucell er niet expliciet bijstaat).

M.b.t. RTS,S, klopt,daar staat ook duidelijk GSK.
M.b.t. Vanderbilt University gaat het IMO wel degelijk over Crucell, nogmaals:

Adenovirus Vaccine for Malaria
This study is not yet open for patient recruitment.
Verified by National Institute of Allergy and Infectious Diseases (NIAID) August 2006

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00371189
The study’s purpose is to find out if a new malaria vaccine is effective, safe, and tolerated in healthy adults 18 to 45 years of age. The vaccine is expected to be tolerated in humans and boost immunity to malaria. At least 96 healthy male and female volunteers will participate in this study at Vanderbilt University Medical Center in Nashville, TN. Volunteers will receive 3 doses of either the new malaria vaccine being or a placebo (contains no vaccine) by injection into the shoulder muscle at 0, 1 and 6 months. Investigators will look at the safety and effectiveness of increasing dosage strengths of the vaccine. Increasing the dosage will proceed only after a review of the 2-week safety data of the 2 initial doses of the prior dosage level. Participants will have 13 study visits and complete a Memory Aid (study diary) at home. Blood will be drawn 7 times from each volunteer during participation in the study. Each participant will be followed for about 1 year.

Condition Intervention Phase
Malaria
Vaccine: Ad35, CS
Phase I

MedlinePlus related topics: Malaria
Study Type: Interventional
Study Design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety Study
Official Title: A Phase I Randomized, Controlled, Dosage-Escalation Trial to Evaluate the Immunogenicity, Safety, and Reactogenicity of an Adenovirus Type 35 Based Circumsporozoite Malaria Vaccine in Healthy Adults 18 to 45 Years of Age
Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Expected Total Enrollment: 96
The purpose of this phase I, randomized, controlled, dosage-escalation trial is to evaluate the immunogenicity, safety, and tolerability of an Adenovirus Type 35 Based Circumsporozoite Malaria vaccine in healthy adults 18 to 45 years of age. At least 96 healthy male and female subjects aged 18 to 64 years will be recruited in Nashville, Tennessee for this study conducted at Vanderbilt University Medical Center. Subjects will be randomized in a 5:1 ratio to receive 3 doses of the Adenovirus Type 35 Circumsporozoite (Ad35.CS) Malaria Vaccine or vaccine formulation buffer control by the intramuscular route at 0, 1 and 6 months. The safety and immunogenicity of ascending dosages of the vaccine will be assessed. Fifteen subjects will receive vaccine at each of the following dosage levels: 10 [to the 8th power] vp/ml and 10 [to the 9th power] vp/ml with three subjects receiving control at each of these dosage levels. Twenty-five subjects will receive vaccine at each of the next dosage levels of 10 [to the 10th power] vp/ml and 10 [to the 11th power] vp/ml with five subjects receiving control at each of these dosage levels. Dosage escalation will proceed only after review of the 2-week safety data of the 2 initial doses of the prior dosage level. The primary objective is to assess the safety and reactogenicity of ascending dosages of Adenovirus Type 35 based circumsporozoite malaria vaccine among healthy subjects given in 3 intramuscular doses at 0, 1 and 6 months. The secondary objective is to evaluate the immunogenicity of the Adenovirus Type 35 based circumsporozoite malaria vaccine through performance of Humoral Immune Assays (ELISA [enzyme-linked immunosorbent assay] for antibodies to circumsporozoite antigen and Adenovirus Neutralization Assay for neutralizing antibodies to Adenovirus type 35) and Cellular Immune Assays (Elispot and Flow Cytometry) for CS-specific CD4+ and CD8+ T cell responses. The primary outcome measure will be frequency and severity of local, systemic, and safety laboratory adverse events. The secondary outcome measures will be: 1) antibody titers against the malaria circumsporozoite antigen via ELISA, 2) neutralizing antibody titers against Adenovirus type 35 by Adenovirus Neutralization Assay, and 3) T cell responses against the malaria circumsporozoite antigen by Elispot and Flow Cytometry.

www.clinicaltrials.gov/ct/show/NCT003...

***********************************
A malaria vaccine is also expected to enter a Phase I trial in the third quarter of 2006 at Vanderbilt University in the US. This randomized, double-blind, placebo-controlled study in 76 healthy volunteers will include dose-escalation studies and multiple vaccination regimens. Studies in large animal models have shown that Crucell's recombinant Ad35 vaccine provides a demonstrated higher level of protection than the existing RTS,S vaccines.
***************
Cohen over ...(pagina 6)
RTS,S
And the search for a malaria vaccine
www.iex.nl/forum/topic.asp?forum=228&...

Uit de posting van go: (pagina 5)
MALARIA PRIME/BOOST VACCINES
v3.espacenet.com/textdoc?DB=EPODOC&ID...

Ook interessant:
www.iex.nl/forum/topic.asp?forum=228&...
**************
M.b.t. Crucell/GSK/WRAIR/NIAID --> live recombinant Ad-CSP.
www.who.int/vaccine_research/document...

[verwijderd] 3 oktober 2006 09:40

0

quote:
flosz schreef:
M.b.t. Vanderbilt University gaat het IMO wel degelijk over Crucell, nogmaals:

Denk het ook hoor. Ik meen me zelfs te herinneren dat Crucell zelf ooit heeft aangegeven/toegelicht met Vanderbilt samen te gaam werken voor Malaria trials....

'k Wou slechts wat toelichting geven op de kale data, en middels berichtje wat nieuwe info verschaffen die er op duidt dat er ergens nog steeds een gecombineerde GKS/Crucell trial in de lucht hangt...

diederique 8 oktober 2006 22:24

0

D/

"There's often a lack of ability to treat people suffering from severe malaria," says Professor Wahlgren. "We've developed a substance that might be able to help these patients."

=======================================
New Treatment For Severe Malaria

Article Date: 03 Oct 2006 - 8:00am (PDT)

|The most dangerous form of malaria is difficult to treat and claims two million lives a year. Now, researchers at Karolinska Institutet in Sweden have developed a powerful new weapon against the disease.

Severe anaemia, respiratory problems and encephalopathy are common and life-threatening consequences of serious malaria infection. The diseases are caused when the malaria bacteria P.falciparium infects the red blood cells, which then accumulate in large amounts, blocking the flow of blood in the capillaries of the brain and other organs.

The reason that the blood cells conglomerate and lodge in the blood vessels is that once in the blood cell the parasite produces proteins that project from the surface of the cell and bind with receptors on other blood cells and on the vessel wall, and thus act like a glue. The challenge facing scientists has been to break these bonds so that the infected blood cells can be transported by the blood stream into the spleen and destroyed.

The research group, which is headed by Professor Mats Wahlgren, has now developed a substance that prevents infected blood cells from binding in this way. The substance also releases blood cells already bound. Using this method, scientists have been able to treat severe malaria in rats and primates effectively; it now remains to be seen whether these results can be replicated in people.

"There's often a lack of ability to treat people suffering from severe malaria," says Professor Wahlgren. "We've developed a substance that might be able to help these patients."

Previously, an anti-coagulant called heparin was used in the treatment of severe malaria. Heparin was able to release the blood cells, but it was soon withdrawn when it was shown that the substance caused internal bleeding. The new substance is a development of heparin, and has the important difference of having no effect on normal blood coagulation.

The study, which is jointly financed by Swedish International Development Cooperation Agency and Dilafor AB, was presented on 29 September in PLoS Pathogens.

Publication:

"Release of sequestered malaria parasites upon injection of a glycosaminoglycan," Anna M. Vogt, Fredrik Pettersson, Kirsten Moll, Cathrine Jonsson, Johan Normark, Ulf Ribacke, Thomas G. Egwang, Hans-Peter Ekre, Dorothe Spillmann, Qijun Chen and Mats Wahlgren, PLoS Pathogens, September 2006, Vol. 2, Issue 9, e100.

For further information, please contact:

Professor Mats Wahlgren
Postdoc Anna Vogt

[verwijderd] 9 oktober 2006 06:06

0

quote:
maxen schreef:
'k Wou slechts wat toelichting geven op de kale data, en middels berichtje wat nieuwe info verschaffen die er op duidt dat er ergens nog steeds een gecombineerde GKS/Crucell trial in de lucht hangt...

Gewoon een e-mail sturen ter verificatie...

[verwijderd] 14 oktober 2006 09:38

0

Public release date: 13-Oct-2006
Contact: Marie Guillaume-Signoret
fichesactu@paris.ird.fr
33-014-803-7607

Institut de Recherche Pour le Développement
Malaria: Efficacy of monotherapies in Cameroon

Malaria, which affects about 600 millions people in the world, is the most widespread of the transmissible parasitic diseases. The causative agent is a microscopic parasite of the genus Plasmodium. The species P. falciparum induces the most serious form of this disease. Since the 1980s, African countries where malaria is endemic have been seeing the emergence of parasite forms resistant to the most widely used treatments, especially to chloroquine. Monitoring of the extent and distribution of such resistance therefore appeared necessary, in order to devise combined treatments (bitherapies) for controlling the disease.
With this objective in mind, researchers from IRD and OCEAC, in conjunction with the Cameroon Ministry of Public Health, assessed the efficacy of the antimalarial treatments most commonly used in Cameroon. In this country, because of the great diversity of landscapes and climates, the patterns of transmission of Plasmodium by mosquitoes differ according to the region, which makes it difficult to track changes and development in resistance (1).
The researchers determined the response in children with malaria, from 12 towns and villages in Cameroon, to three different monotherapies: two habitually prescribed as first treatment in that country (chloroquine and amodiaquine) and one issued as second intention medicine (sulfadoxine-pyrimethamine). The ineffectiveness of chloroquine was rapidly confirmed, with a very high proportion of therapeutic failure (48.6% on average), greater in the south than in the north of the country. That signalled a pressing need to rectify the treatment of the children concerned as soon as possible. This drug can no longer be considered a reliable treatment in Cameroon and its withdrawal from the market by the country's health authorities (in 2002) is justified. However, amodiaquine and, to a lesser extent, sulfadoxine-pyrimethamine are still effective treatments, with low therapeutic failure rates (an average of 7.3 and 9.9% respectively) obtained for the whole set of sites studied. In order to avoid the development of new resistance, these treatments must however be combined with the most recent therapies using artemisinine derivatives, for which no form of resistance currently exists. Amodiaquine, which is generally administered as soon as the first malaria symptoms appear, seems to be the best candidate for these combinations of therapies.
The series of investigations was run from 1999 to 2004, following a protocol established by the WHO (World Health Organization), which advocates regular clinical examination and blood tests for each patient, for 14 days. This protocol enables clinicians to take into account the whole range of factors governing the parasite-host interaction (such as acquired immunity, pharmacokinetics, synergy between constituents, and also the degree of chemoresistance of Plasmodium). However, implementation of this has proved a long and intricate process in Cameroon, where transmission does not have the same pattern and rate of development everywhere. Faced with these constraints, the researchers turned to molecular markers, quick and practical to use for resistance assessment (2). They used the blood samples taken from the different sites under study to estimate the degree of resistance to pyrimethamine, one of the components of sulfadoxine-pyrimethamine. The sequence of a particular gene of Plasmodium (dhfr, dihydrofolate reductase gene) was analysed, in the search for occasional mutations that might provide the parasite with resistance to this agent. The proportion of strains of mutant Plasmodium in the samples is thus a direct expression of the resistance.
Geographical mapping of the occurrence of pyrimethamine resistance was subsequently conducted. The frequency of mutant resistant strains and the number of mutations were plotted for the different areas. The data obtained, such as the lower proportion of these resistant strains observed in the north than in the south of Cameroon, complement the results of clinical investigations. The research team has since then launched similar work, focused especially on the gene for resistance to sulfadoxine, the other constituent of the sulfadoxine-pyrimethamine mixture.
The molecular approach, adapted to the varied epidemiological backgrounds that prevail in Cameroon, is therefore highly promising as a tool for tracking the evolution of resistance to monotherapies and thus for helping to improve malaria control strategies.
(1) Cameroon, with a surface area of 475 442 km2, is situated deep in the Gulf of Guinea, a region where Central Africa and West Africa meet. This geographical situation explains the great variety of climates and landscapes which make the country a kind of "Africa in miniature" (www.diplomatie.gouv.fr/fr/payszones- geo_833/cameroun_361/presentation-ducameroun_ 946/geographie_8432.html). In the north, dominated by vast plains, malaria transmission is seasonal. In the south, characterized by the presence of vast forest, it occurs continuously and intensively.
(2) In the standard surveys on therapeutic efficiency, just one drug or a single combination was tested simultaneously, in each patient and each locality, by a specialist mobile team. In the north of Cameroon where transmission is seasonal, this team's expeditions into the field had to be carefully planned. However, in the genetic approach, the collection of capillary blood on absorbent paper does not require any specialized team. A local team of local care providers gathers all samples together and sends them to the laboratory. The search for specific resistance markers can be carried on at the same time for several substances in uniform conditions.
###
www.eurekalert.org

[verwijderd] 19 oktober 2006 08:22

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Experimental malaria vaccine shows huge promise

00:01 18 October 2006
NewScientist.com news service
Debora MacKenzie
A review of experimental malaria vaccines has found that one shows such promise, the results “justify speedy progress towards licensing for routine use”. That would make it the first-ever commercial vaccine against one of the world’s deadliest diseases – but it may need to be used along with other kinds of malaria vaccine to really stop the killer.
Malaria is a parasite carried by mosquitoes, and is thought to have killed more humans throughout history than any other disease. It now kills at least a million people a year, especially children in Africa, and increasingly resists anti-malarial drugs.
Efforts to develop a vaccine have been frustrated because the parasite changes its form several times during an infection. These changes alter the surface chemicals that vaccines normally exploit to prime the immune system to recognise a pathogen. Scientists are divided over which stage to vaccinate against.
Vaccinating against the first stage, the sporozoite, which enters the blood from the mosquito, might prevent infection entirely. But the immune system would have a limited time to work before the parasite changes into the next stage, the merozoite, which enters red blood cells. Vaccinating against merozoites would not prevent infection, but might limit disease.
The Cochrane Collaboration, an organisation that reviews clinical trials, has looked at recent experiments with four leading candidates for a sporozoite vaccine. Three, it said, show no clear effect. One, however, showed effectiveness.
Best protection yet
It consists of a large chunk of a surface protein from sporozoites which the scientists attached to a surface protein from the hepatitis B virus. The virus part stimulates the immune system, while the pathogen part primes the immune system to attack the sporozoite.
The vaccine protected 41% of volunteers in the US who were exposed to malarial mosquitoes in the lab. When it was tried on children in Mozambique, it cut malaria cases by 26% for 18 months after vaccination – and cut the severity of the illness by more than half (see New malaria vaccine raises high hopes). In Gambia, men given two shots, one year apart, suffered 63% fewer cases.
That is poor protection compared with the near-complete protection associated with polio or measles vaccines, but it is the best so far against malaria, the reviewers say, and means the company that owns it, Smith Kline Beecham, should get it into commercial use soon.
Protection might be better if the sporozoite vaccine can be combined with one against merozoites, thus hitting the parasite twice. In a separate review in the same issue of the Cochrane journal, the researchers report that the only merozoite vaccine so far tested for effectiveness did not reduce rates of illness in children in Papua-New Guinea. But it did cut the number of parasites in their blood.
Journal reference: The Cochrane Database of Systematic Reviews (2006, issue 4)
www.newscientist.com/article/dn10318-...

*************************************
The vaccine, named RTS,S/AS02A carries two short proteins, called RTS and S, mimicking a key surface component of the sporozoite usually recognised by the immune system.
www.newscientist.com/article/dn6537

[verwijderd] 19 oktober 2006 08:35

1

Leesvoer...5 pag.!

Breaking the Cycle
The U.S. Army and its partners have been trying to develop a malaria vaccine for decades. But given a disease that has thwarted man for centuries and gets scant attention from the West, is this a battle they can win?
By Michael LeahySunday, October 8, 2006; Page W16

TO REACH THE SPECIAL MOSQUITOES, an Army researcher like Gray Heppner must walk through seven heavy doors off a corridor at Walter Reed Army Institute of Research in Silver Spring. The mosquitoes, called Anopheles gambiae , are behind that last door, in meshed cartons. They don't fly much in their confined space and appear quite benign in this room where everything feels unremarkable, even the high heat and humidity, which are meant to mimic the sweltering environs in which the anopheles thrives.
Only the unusual routines of the area, known as the insectary, belie the air of ordinariness. No two doors out of these seven are ever to be opened at the same time -- this to guard against the escape of any mosquitoes, which have been infected with malaria parasites by Army lab technicians. Just in case, small plastic bags, illuminated by an icy-blue light, hang between all the doors -- mosquito traps guarding against the remote chance that an anopheles gets loose. If a fugitive mosquito ever made it beyond all seven doors, it would be an unprecedented event, an entomological feat akin to an escape from Alcatraz.
By conservative estimates, malaria claims more than 1 million lives globally each year, 90 percent of them in sub-Saharan Africa, the vast majority children. Young survivors are frequently left with cognitive damage that can cause them to fail at school and work. African adults, while having lived long enough to gain some immunity against malaria's worst effects, often lose weeks of work while recovering from the disease. Western economists estimate that malaria results in an economic loss of $12 billion annually in Africa, the continent least able to foot the bill for fighting the disease.
But in the consciousness of the average Westerner or in the official discourse of a governmental body such as the U.S. Congress, the scourge hardly registers -- a relic, like polio. Although affecting regions that make up about 40 percent of the planet, malaria is overshadowed by diseases that directly touch the West, such as AIDS, and worries about possible pandemics, such as bird flu. With U.S. government funds scarce, Heppner is vying with rival malaria vaccine researchers -- and rival approaches to fighting the disease -- for public attention and private research dollars, most of which come from philanthropic organizations with deep pockets, such as the Bill and Melinda Gates Foundation. As a colonel and the chief of Walter Reed's department of immunology and its malaria vaccine research program, Heppner's ultimate ambition is simple: Create a vaccine that will prevent infection and eradicate malaria in the way that Jonas Salk's vaccine wiped out polio in most places.
But malaria vaccine research must always compete for funding against more conventional methods for battling the disease, such as antimalarial drugs and insecticide-treated bed nets, as well as methods still in development -- including dreams of sterilizing mosquitoes and of making a vaccine to stop the transmission of parasites from an infected human to a healthy mosquito, thereby breaking the cycle of disease.
This particular summer day marks the launch of what Heppner estimates to be the 30th clinical trial of a malaria vaccine since the Walter Reed program began in 1983. There have been a lot of colossal failures. In the early '90s, not long after he accepted a position in the malaria program, an eager Heppner volunteered to take a shot of a prospective vaccine and allow himself to be bitten by an infected mosquito, as part of a clinical trial. The vaccine failed, and Heppner contracted malaria, after which an antimalarial drug treatment left him disoriented and suffering from nightmares for a couple of days.
But vaccine makers, like oil men and gold diggers, never stop dreaming. Sixteen years after he started at Walter Reed, Heppner's hopes are higher than ever in the wake of promising test results from a vaccine called RTS,S, which Walter Reed helped develop with a prominent pharmaceutical company, GlaxoSmithKline Biologicals.
In this latest clinical trial, Heppner and other Walter Reed researchers will evaluate another vaccine candidate, different from RTS,S and not yet publicly identified. Its potency in mice has fueled confidence at Walter Reed and brought 28 visitors to the insectary. They are the clinical trial's volunteers, drawn in some cases by newspaper advertisements. Others were recruited by Walter Reed personnel or heard about the trial from friends. According to Walter Reed staff members, 22 of the 28 participants have already received two doses of the vaccine.
The vaccine's inventor, David Lanar, is an Army researcher who has worked for years with others at Walter Reed to make the vaccine ready for clinical trials. Their efforts have cost several million dollars, in a field where government funding is hard to come by; one contributor, the Department of Defense, annually allocates $8 million (about .002 percent of the Defense budget) for malaria vaccine research, equally divided between Heppner's Army unit and a similar Navy group. The stakes of this trial feel high to Lanar. "There are only so many chances that [a researcher] will get in a career to make a vaccine," he says.
He has been in this position before. In the early '90s, he created another vaccine, NYVAC-7, whose possibilities thrilled Heppner and others during early testing. Lanar fleetingly pondered the possibility that he might become famous: The Man Who Cured Malaria. "I could see myself on the cover of Science [magazine]," Lanar remembers, smiling. But then the vaccine failed. "It was pretty devastating."
Now waiting on the test of his new vaccine, Lanar is no less daunted by the challenge. "The parasites have learned how to withstand desperate attempts to eradicate them for thousands of years," he says. "They've survived the attempts of the body's [immune system] to wipe them out for millions of years."
Nearly all the volunteers know that human beings can be infected by four species of malaria parasites, the most dangerous of which, the one responsible for virtually all malaria deaths around the world, Plasmodium falciparum , is the parasite carried by the mosquitoes behind door seven. The volunteers understand that if the vaccine doesn't work, even those treated quickly are likely to experience a few days of nasty flu-like symptoms that could include screaming headaches, high fever, chills and vomiting fits. Some admit to feeling spooked ever since they volunteered to be bitten by an infected anopheles.

Lees verder via:

www.washingtonpost.com/wp-dyn/content...

[verwijderd] 20 oktober 2006 11:39

0

First malaria research centre to be set up in the capital
By a staff reporter

20 October 2006
ABU DHABI — The Higher Colleges of Technology (HCT) has signed a memorandum of understanding (MoU) with the Swiss non-profit organisation, Medicines for Malaria Venture (MMV), to explore the opportunity of participating in the proposed Abu Dhabi Bio City.
As per the agreement, the HCT is aspiring to be a leading participant in a new centre on Malaria Research and Development, Distribution and Education that will be set within the planned Abu Dhabi Bio City.
The centre, which will be completed by 2009, seeks to make a significant impact on the discovery and development of novel anti-malarial agents and their subsequent distribution in the major regions of the Indian Ocean basin (where malaria is endemic) including the GCC, the broader Middle East, East Africa and the Indian sub-continent.
Drug discovery, drug distribution, professional medical education and positive policy change for all the regions in the world affected by malaria are the primary goals of the centre.
The MoU was signed by Shaikh Nahyan bin Mubarak Al Nahyan, Minister of Higher Education and Scientific Research and Chancellor of the HCT, and Baroness Lynda Chalker of Wallasey, MMV's Board Chairperson. The MMV is a non-profit national foundation established to discover and disseminate new therapeutic modalities for the treatment and ultimate eradication of malaria.
"This is a very important initiative for the UAE to help and contribute to the effective prevention, timely treatment and eventual elimination of this dreadful disease that attacks thousands of people including children around the world. We are pleased to join forces with several leading international organisations in this noble cause," said Shaikh Nahyan after signing the joint pact. Commenting on the agreement, Dr Tayeb Kamali, Vice-Chancellor of HCT, said such projects are in line with the increasing commitment and engagement of HCT in applied research projects for the benefit of the community and the region at large.
www.khaleejtimes.com/DisplayArticle.a...

Zie ook:
www.mmv.org/article.php3?id_article=317
www.iex.nl/forum/topic.asp?forum=228&...

Medicines for Malaria Venture (MMV)
A nonprofit organization created to discover, develop and deliver new antimalarial drugs through effective public-private partnerships.
Our vision is a world in which affordable drugs will help eliminate the devastating effects of malaria and help protect the billions of people, especially children and pregnant women, at risk of this terrible disease.
www.mmv.org/rubrique.php3?id_rubrique=15

[verwijderd] 20 oktober 2006 12:32

0

quote:
flosz schreef:
Leesvoer...5 pag.!

www.washingtonpost.com/wp-dyn/content...

Zeer lezenswaardig. Een blik naar binnen bij Walter Reed. Geweldig gemotiveerde mensen...

[verwijderd] 23 oktober 2006 10:36

0

In afwachting start Phase I trial,( www.clinicaltrials.gov/ct/show/NCT003... , Adenovirus Vaccine for Malaria at Vanderbilt University, zie pagina 9),
de "Gouden" samenvatting m.b.t.: (Immunogenicity and Protection of a Recombinant Human Adenovirus Serotype 35-Based Malaria Vaccine against Plasmodium yoelii in Mice, van Biocon erbij:

Biocon - 24 dec 05, 14:43

Hierbij dan de beloofde samenvatting van het artikel over malariavaccins in muizen. Met dank aan Stefan en Babs voor het mailen van het volledige artikel. Wat zijn we zonder elkaar?

Het maken van een malaria vaccine is tot nu toe altijd onmogelijk geweest omdat er productie problemen zijn met het groeien van geinactiveerde parasieten. Het huidige, meest kansrijke vaccine is RTS,S met adjuvant AS02A (van GSK) en bied 30-40% bescherming in trials in Afrika. Het wekt een sterke antilichaam respons op maar de T cel respons is zwak, kortdurend en er worden nauwelijks geheugen responses opgewekt.
rAd5 is een van de meest belovende vectoren voor een vaccine omdat het sterke T en B cel responses op kan wekken en makkelijk te produceren valt. Een nadeel is echter (oa gebleken uit de Ad5-HIV trials) dat neutralizerende antilichamen in het bloed van de patient de anti-HIV respons verminderde. Ad35 vectoren lopen veel minder kans te worden geneutraliseerd en kunnen nog steeds een krachtige antiHIV response in een muizenmodel opwekken ondanks de aanwezigheid van Anti-Ad5 antilichamen.

In deze studie wordt gekeken in een muizen model of dit systeem ook werkt voor malaria.

Allereerst is naar sera gekeken bij 153 personen uit 20 Afrikaanse landen. Het bleek dat 85% neutraliserende antilichaam activiteit had tegen Ad5 terwijl tegen Ad35 minder dan 20% die activiteit had. Daarnaast was de antiAd35 activiteit ook nog eens 20x lager dan tegen Ad5. Dus: goede mogelijkheden voor Ad35 vaccines.

Muizen werden vervolgens ingespoten met Ad35-CS en Ad5-CS, de vector met een stukje parasieten DNA (The circumsporozoite
(CS) protein insert in both rAd5PyCS and rAd35PyCS consisted of amino acids 1 to 356 of the CS protein of P. yoelii placed under the control of a cytomegalovirus promoter). Er werd een duidelijk anti-CS T cel activiteit en antilichaam productie (uit B cellen) gemeten voor beide vectoren, waarbij voor Ad35 de maximale respons hoger was bij een hogere dosis.

In het volgende experiment werd bij dezelfde dosis een hoge T cel respons gemeten. Voor Ad35CS is die efficienter dan voor Ad5CS, maar voor B cel responses is het andersom. Het bleek echter ook dat na vaccinatie met Ad35CS er nog veel minder parasieten in de lever van de muizen aanwezig waren dan na Ad5CS vaccinatie en dat het mechanisme dus via de T cellen verloopt.

Daarna werd dezelfde vaccinatie uitgevoerd, echter na eerst een lege Ad5 te hebben ingespoten om zo Ad5 neutralizerende antilichamen op te wekken. De Ad5 T cel response waren nu 4x zo laag terwijl er geen effct op het Ad35 vaccin gemeten werd. Ook de B cel response door Ad5CS opgewekt was nog maar 5% van die in muizen zonder neutralizerende antilichamen.

Prime-boost strategien werden vervolgens gemeten:
Ad35CS-Ad35CS, Ad35CS-Ad5CS en Ad5CS-Ad35CS met 8 weken als tussenpoos. De heterologe prime boost schama werkten duidelijk het best omdat de opgewekte neutralizerende antilichamen bij de prime (tegen Ad5 of Ad35) de boost (Ad35 en Ad5) niet neutraliseren. Dit gold voor zowel T als B cel responsen en infectie van de lever met parasieten (94% minder vs 62% in het geval van Ad35-Ad35 PB).

Voor zover de proeven.
De discussie gaat over enkele zaken hierboven reeds aangehaald. In het volgende stuk wordt nog eens geopperd dat een prime boost met GSK’s vaccine een mogelijkheid is om die repsonse op te krikken en dan met name de T cel response, maar dat heterologe Ad5-Ad35 minstens zo goed zo kunnen zijn. Met de opmerking erbij dat ipv Ad5 dan een andere Ad zou moeten worden gebruitk omdat Ad5 neutralizerende antilichamen in de afrikaanse bevolking een te grote drempel zullen zijn.

Kortom een gedegen studie met goede resultaten en inderdaad zelfs de suggestie dat een malaria vaccin zelf kan worden gemaakt zonder GSK.

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

[verwijderd] 24 oktober 2006 16:14

0

SCIENTISTS PREPARE PIONEERING MALARIA VACCINE
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GRAEME BROWN

09:40 - 21 October 2006
Scientists in North Staffordshire are working on a new vaccine which could stop millions of people dying from malaria.Keele-based Cobra Biomanufacturing will work with the Naval Medical Research Center in the U.S. to develop an oral vaccine for the disease which, according to Department for International Development statistics, kills up to 2.7 million people a year.

The company will apply its technology to convert injection vaccines sent across from Washington DC into a water-soluble powder which protects people from contracting the parasitic disease.

Chief executive David Thatcher said: "If it worked very well then it would be a massive, blockbuster vaccine product.

"Malaria is a huge disease, but it is largely a disease of the developing world.

"Traditional vaccines are very expensive whereas this is potentially very cheap.

"We have got into bed with the U.S. Navy who have a huge municipal centre in Washington which is one of the world's centres of excellence for medical research."

In trials last year, Cobra showed it was able to protect animals against plague with an oral vaccine.

It now plans to use the same technology to create the malaria vaccine in North Staffordshire before sending it to Washington DC for testing.

Mr Thatcher said it would take up to two years to create, five to eight years to take it to market and would be manufactured in North Staffordshire.

If the trials are successful it could have a huge impact as the disease has become a growing problem in sub-Saharan Africa, where there are more than 200 million cases a year.

Mr Thatcher said: "The advantage is being easy to manufacture - it would bring the cost down so the developing world would benefit from it.

"And in the West there is a growing problem with tourists picking up malaria because people are going on holiday to areas like Kenya."

Peter Chiodini, consultant parasitologist at the London School of Hygiene and Tropical Medicine said the international health community is desperate for an effective malaria vaccine.

He said: "At the moment we don't have a malaria vaccine on the market.

"They have been trying for decades but the parasite is very difficult because it changes its antigens.

"If this proves to be an effective vaccine it will be a very valuable addition. It is a top priority."

Cobra declined to reveal the financial value of the deal, but Mr Thatcher said it could be 'transforming' if the vaccine went into production.

Last week, it announced a 33 per cent rise in half-year turnover, to £5.7 million on the back of increased U.S. sales.

[verwijderd] 25 oktober 2006 18:37

1

NMRC-M3V-Ad-PfCA Vaccine - Clinical Trial 1
This study is currently recruiting patients.
Verified by Walter Reed Army Institute of Research (WRAIR) October 2006

Sponsors and Collaborators: U.S. Army Office of the Surgeon General
United States Agency for International Development (USAID)
Congressionally Directed Medical Research Programs (CDMRP)
Military Infectious Diseases Research Program (MIDRP)
Information provided by: Walter Reed Army Institute of Research (WRAIR)
ClinicalTrials.gov Identifier: NCT00392015

The purpose of this study is to determine whether a new investigational malaria vaccine is safe, well tolerated and effective against experimental exposure to malaria when given to healthy people with no previous exposure to malaria. The vaccine consists of a modified form of a relatively common virus, adenovirus, that has been rendered incapable of replicating itself and modified to deliver the malaria gene of interest to the body’s cells allowing the cell to manufacture the protein encoded by the gene and present it to the body’s immune system in a more natural and presumably effective way.
clinicaltrials.gov/show/NCT00392015

[verwijderd] 25 oktober 2006 18:53

0

Malaria vaccine may be ready by 2010

October 25 2006 at 01:55AM

Maputo - The first vaccine against malaria could be on the market by 2010 following trials in Mozambique, the southern African country's deputy health minister told an international conference on Tuesday.

"We think the first malaria vaccine will be available by 2010 if the tests in Manhica (north of the capital Maputo) are effective," Aida Libombo told the gathering of health professionals.

"We hope that the future vaccine will benefit the local population and be affordable," the minister said, adding it would cost about $60-million to develop it.

Mozambican officials announced in July 2002 that they had begun testing a drug that could be developed into a malaria vaccine on several people.

Some four million Mozambicans suffer from malaria every year on an average, according to the health ministry. One out of 10 patients eventually die.

Mozambique spends about six million dollars every year in efforts to fight malaria. - Sapa-AFP
www.iol.co.za/index.php?set_id=14&cli...

bilbo3 25 oktober 2006 20:02

0

ik ben een beetje confused.

inzake malaria werkt Crucell samen met enerzijds NIH en anderzijds met WRAIR/GSK.

In dit draadje kom ik verwijzingen naar twee trials tegen. Eentje met de NIAID en is nog niet geopend voor patient recruitment, en eentje met WRAIR, welke wel geopend is voor patient recruitment.

Zijn nu beide trials in samenwerking met Crucell en krijgen we dan tzt twee vaccins die de clinic ingaan?

Wie kan me dit uitleggen??

Jan

gogogoo 25 oktober 2006 20:37

1

quote:
bilbo3 schreef:
ik ben een beetje confused.

inzake malaria werkt Crucell samen met enerzijds NIH en anderzijds met WRAIR/GSK.

In dit draadje kom ik verwijzingen naar twee trials tegen. Eentje met de NIAID en is nog niet geopend voor patient recruitment, en eentje met WRAIR, welke wel geopend is voor patient recruitment.

Zijn nu beide trials in samenwerking met Crucell en krijgen we dan tzt twee vaccins die de clinic ingaan?

Wie kan me dit uitleggen??

Jan

Zie attachment: dit is die van de WRAIR/GSK.
fermat.nap.edu/books/0309101689/html/...

Bijlage:

gogogoo 25 oktober 2006 20:47

0

Malaria Vaccine Program

Crucell is developing a recombinant malaria vaccine based on its proprietary AdVac® technology and produced on its proprietary PER.C6® production technology.

Press Releases mbt Malaria:

1 Aug. 2005: Harvard and Crucell Receive $19.2 million NIH Grant to Develop Next-Generation AdVac®-based Vaccines

23 Dec. 2004: Crucell Secures € 2 Million Grant for Malaria Collaboration from Dutch Ministry of Economic Affairs

30 March 2004: Crucell Receives NIH Support for Candidate Malaria Vaccine Development

14 Nov. 2003: Crucell Presents Encouraging Results of its Malaria Vaccine Program

22 Oct. 2003: Crucell Announces Malaria Vaccine Program in Collaboration with New York University, Walter Reed Army Institute of Research and GlaxoSmithKline

[verwijderd] 26 oktober 2006 11:31

6

quote:
Bilbo3 schreef:
ik ben een beetje confused.
[/quote]

OK dan, hier wat toelichting op de neergekwakte linkjes:

Deze trial, van NIAID (onderdeel van NIH) met Ad35 adenovirus is zeer waarschijnlijk met Crucell, en uitgevoerd door Vanderbilt University:

[quote=flosz]
In afwachting start Phase I trial,( www.clinicaltrials.gov/ct/show/NCT003... , Adenovirus Vaccine for Malaria at Vanderbilt University, zie pagina 9),
de "Gouden" samenvatting m.b.t.: (Immunogenicity and Protection of a Recombinant Human Adenovirus Serotype 35-Based Malaria Vaccine against Plasmodium yoelii in Mice, van Biocon erbij:
[/quote]

Deze, van NMRC (Naval Medical Research Center), waarin ook Walter Reed zijdelings wordt genoemd, is met Ad5 vector met daarin dna codes voor CSP en AMA eiwit. Hieronder zal blijken dat de Ad5 zeer waarschijnlijk van Genvec komt, en niet van Crucell:
[quote=flosz]
NMRC-M3V-Ad-PfCA Vaccine - Clinical Trial 1
This study is currently recruiting patients.
Verified by Walter Reed Army Institute of Research (WRAIR) October 2006
...
clinicaltrials.gov/show/NCT00392015

(ingekorte) info over dit vaccin uit deze link - Maxen:
"The vaccine, called NMRC-M3V-Ad-PfCA, is a combination of two recombinant adenovirus-derived constructs (adenovectors), one expressing CSP, and the other expressing AMA1. The vector is an type 5 adenovirus."
[/quote]
Voor dit Ad5-gebaseerd vaccin van NMRC zie Gogogoo's link (goed gevonden overigens):
[quote=Gogogoo]
Zie attachment: dit is die van de WRAIR/GSK.
fermat.nap.edu/books/0309101689/html/...
[/quote]

Daarin de beschrijving van NMRC's verschillende benaderingen tot malaria vaccins door het gebruik van verschillende 'subunits', oftewel de antigens:
[quote= boek getiteld "Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program (2006)"]
The following are the specific subunit approaches:
-Plasmid DNA
-Adenovirus 5 vectors in collaboration with Genvec, with two to five antigen sequences (CSLAM or some of its consituent antigens) used in DNA priming and vector boosting
-Poxvirus
-Alphavax
-viral priming followed by recombinant protein boosting, in collaboration with NIH Malaria Vaccine Development unit and WRAIR (Walter Reed)
(klinkt Crucellig - Maxen)
-multiepitope

The NMRC has immediate plans for a phase 1 clinical trial of the adenovirus 5/CSP + AMA-1 construct in US volunteers in the near future, followed by trials of different prime-boost combinations of DNA and adenovirus 5 constructs for CSP/AMA-1.

(Maxen's commentaar: Door de 100% overeenkomst is het duidelijk dat dit het vaccin betreft uit Flosz NMRC clinical trials link. Gezien bovenstaande text met 2 tot 5 antigens gecodeerd door GenVecs Ad5 is het ook duidelijk dat deze Ad5 vectoren dus van GenVec komen)

The WRAIR scientists have also been investigating heterologous prime-boost regimens, in which different immunogens are used for prime versus boost, to further optimize immune responses. WRAIR is collaborating with Crucell and GSK in exploring use of Ad35 virus expressing CSP to boost RTS,S primed responses (although these studies are contingent on resolving intellectual property isssues of both companies).

Dit laatste deel slaat dus overduidelijk op Crucell. Hier wordt Ad35 gebruikt dat codeert voor CSP, samen met GSK's RTS,S eiwit. Sponsor is hier WRAIR, en niet NMRC. Hier wordt (weer eens)duidelijk dat voortgang van een clinical trial hiervoor afhangt van de "issues" tussen Crucell en GSK. Dus vooralsnog GEEN clinical trial voor deze combinatie.

Samengevat:

De NIAID/Crucell/VanderBilt clinical trial op basis van Ad35/CSP kan elk ogenblik beginnen.

De WRAIR/Crucell/GSK clinical trial op basis van Ad35/CSP en RTS,S komt er niet zolang Crucell en GSK hun "issues" over geld niet oplossen.

De NIAID/GenVec trial op basis van Ad5/CSP en Ad5/AMA1 is onlangs begonnen.

NIAID en WRAIR zijn twee concurerende Amerikaanse overheids/militaire onderzoek-instellingen, elk met hun eigen onderzoek en samenwerkingen. Ze werken ook wel samen met elkaar.

Hopelijk helpt dit tegen alle confusion.

Maxen.

[verwijderd] 26 oktober 2006 11:42

0

quote:
maxen schreef:
De NIAID/GenVec trial op basis van Ad5/CSP en Ad5/AMA1 is onlangs begonnen.

NIAID en WRAIR zijn twee concurerende Amerikaanse overheids/militaire onderzoek-instellingen

Correctie: moet zijn "NMRC/Genvec trial" en "NMRC en WRAIR zijn...."

Uiteraard is NIAID NOG een concurrerende Amerikaanse overheids-onderzoek-instelling....

bilbo3 26 oktober 2006 12:38

0

Gogogo en Maxen bedankt,

ik ben weer een stuk wijzer

Jan

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