Crucell « Terug naar discussie overzicht

draadje Malaria

439 Posts, Pagina: « 1 2 3 4 5 6 ... 14 15 16 17 18 19 20 21 22 » | Laatste
[verwijderd]
0
Het lijkt er wel op dat niemand de aandelen meer kwijt wil. Men tracht een significante stijging tegen te houden, alsof de boel op ontploffen staat.Misschien overdrijf ik wel, maar een eerste come-back naar €15,00 zou mooi zijn.
[verwijderd]
0
Zonder meer positief nieuws, ben benieuwd hoe daar vanmiddag in de US op wordt gereageerd.
flosz
2
Kan dit svp ergens anders?
Hier www.iex.nl/forum/topic.asp?forum=228&...
of daar
www.iex.nl/forum/topic.asp?forum=228&... bv!

Of nog iets interessants te melden mbt: "At this moment in time, we are again on speaking terms and world needs a very good malaria vaccine and the RTSS from Glaxo so far did not go beyond an efficacy number of 50%.
We believe using it has a prime boost in combination with our vaccine will draw the efficacy up to 80%."
aossa
0
quote:

Dirk R. Wijnen schreef:

Deed GSK dat niet samen met Crucell?

Dirk
The GSK malaria vaccine candidate RTS,S has, as a stand-alone vaccine, 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 the Gambia. Phase IIb pediatric trials conducted with RTS,S in Mozambique and reported in The Lancet medical journal in October 2004 and 2007 demonstrated 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.
www.crucell.com/R_and_D-Clinical_Deve...

Met Crucell boost erbij +90% effectiviteit!
Eerst Crucell boost vaccines, daarna 1 en 3 maand later het GSK vaccine.
Na goedkeuring van het GSK vaccine heeft Crucell de handen vrij om het open label te testen, dat is het goede nieuws imo.

Q: hoe zit het met resistentie-opbouw indien GSK alleen gaat worden toegepast met <50% effectiviteit?
Bijlage:
[verwijderd]
0
[quote=aossa]
[quote=Dirk R. Wijnen]
Deed GSK dat niet samen met Crucell?

In a study carried out by New York University (NYU), the efficacy of our malaria vaccine candidate was tested in NYU’s mouse malaria model. The study showed that a single administration of a prototype AdVac® vaccine protects mice upon challenge with the mouse specific parasite.

In March 2003, we entered into collaboration with the Walter Reed Army Institute of Research (WRAIR) and GlaxoSmithKline Biologicals (GSK) under a Cooperative Research and Development Agreement (CRADA). In line with this agreement, we have completed work with WRAIR and GSK to evaluate our AdVac® malaria vaccine candidate. Our vaccine candidate was tested as a stand-alone vaccine and in combination with GSK’s RTS,S malaria vaccine candidate. These studies have shown that Crucell’s AdVac® vaccine candidate efficiently primed and/or boosted malaria specific immune responses.

The GSK malaria vaccine candidate RTS,S has, as a stand-alone vaccine, 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 the Gambia. Phase IIb pediatric trials conducted with RTS,S in Mozambique and reported in The Lancet medical journal in October 2004 and 2007 demonstrated 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.

flosz
2
[verwijderd]
0
quote:

flosz schreef:

Zie vooral ook de eerste zesendertig pagina's van dit draadje........
:>))))))
[verwijderd]
0
quote:

flosz schreef:

Zie vooral ook de eerste zesendertig pagina's van dit draadje........
LOL
Mr sponge
0
Sanofi-aventis and Medicines for Malaria
Venture to launch the largest ever study
of an antimalarial drug

- Ambitious drug-monitoring program started in Africa -

Paris, France and Geneva, Switzerland – November 19, 2009 – Sanofi-aventis ( EURONEXT: SAN and
NYSE: SNY) and Medicines for Malaria Venture (MMV) announced today that they have entered an
agreement to launch the largest safety and efficacy study of an antimalarial drug. This field-monitoring
program on ASAQ, a fixed-dose combination of artesunate and amodiaquine, started in Côte d’Ivoire in
October 2009. MMV is a not-for-profit drug research and development organization dedicated to reducing
the burden of malaria.
ASAQ is the only fixed-dose combination of artesunate and amodiaquine prequalified by WHO in the
treatment of Plasmodium falciparum uncomplicated malaria. ASAQ is the result of a partnership between
sanofi-aventis and Drugs for Neglected Diseases initiative (DNDi) and was launched in 2007.
“We have designed an innovative field-monitoring program to assess the effectiveness and safety of ASAQ
in real life conditions”, said Robert Sebbag, Vice President, Access to Medicines at sanofi-aventis. “Thanks
to MMV’s support, we are now able to launch in Côte d’Ivoire this large study that completes the most
ambitious drug monitoring program ever launched in Africa”, he added.
Under the terms of the agreement, MMV will provide $1.5 million towards the implementation of this large
field-monitoring study developed by sanofi-aventis and the National Malaria Control Program of Côte
d’Ivoire. Over a two-year period, approximately 15,000 patients afflicted by malaria are expected to be
enrolled. All patients diagnosed with uncomplicated malaria at public health clinics in selected parts of the
Agboville district (approximately 100km north of Abidjan) will receive a prescription of ASAQ. Within a week,
patients will be visited at home by specially trained community health workers to assess treatment
tolerability and compliance.
“Data collected in clinical trials do not always provide the full picture of a new drug’s efficacy and safety. This
large Côte d’Ivoire study will use innovative methods to monitor antimalarial drugs’ efficacy and safety and
generate critical data,” said Dr. Chris Hentschel, President and CEO of MMV. “MMV is pleased to support
this important study. The experience gained with ASAQ in the field will help us design pharmacovigilance
programs for the new antimalarials in our own pipeline.”
Malaria is a fatal infectious disease that causes almost a million deaths a year of which over 90% are in
Africa and 85% are children under the age of five. Most of these deaths are due to lack of access to effective
antimalarials and erratic patient compliance.

About ASAQ
ASAQ, the first fixed-dose combination of artesunate (AS) and amodiaquine (AQ) was developed by sanofiaventis
and the FACT (Fixed-dose, Artemisinin-based Combination Therapy) partners, managed by DNDi.
First registered in Morocco, where it is manufactured, in 2007, it was pre-qualified by the WHO in 2008.
ASAQ is available under the name Artesunate-Amodiaquine Winthrop® (ASAQ) for public markets, and
under the brand name Coarsucam® in private markets.

About the ASAQ field-monitoring program
Drug development studies are conducted under very controlled circumstances that differ enormously from
the situation on the ground. Once a new drug is widely distributed, it is important to monitor its rational use.
Due to the wide distribution of antimalarials and the shortcomings of pharmacovigilance systems in many
endemic countries, post registration studies to assess the safety and efficacy of the product are necessary.
Following the launch of ASAQ in 2007, sanofi-aventis and DNDi decided to set-up a proactive monitoring
plan of the drug’s efficacy and safety in real life conditions: the “ASAQ field-monitoring program”. The Côte
d’Ivoire study is a key component, and the largest study, of this program.
The ASAQ field-monitoring program includes several studies throughout Africa. Each will provide specific
sets of data on ASAQ safety and efficacy using a variety of study designs. These studies have been set up
by sanofi-aventis, by DNDi, or by academic or government institutions, in close collaboration with each
country’s National Malaria Control Program. All the data collected will be aggregated into a single data base
to enable detailed analyses. With over 20,000 malaria episodes to be treated with ASAQ, this is the most
ambitious proactive drug monitoring program ever launched in Africa, for any drug. The WHO Department of
Medicines Policy and Standards has expressed interest in seeing this program formalized as a Risk
Management Plan (RMP) for ASAQ, the first program of this kind to be submitted to the WHO. The
experience gained through this RMP will be useful for future antimalarials that will be launched in developing
countries with relatively limited sets of safety and efficacy data.

About Medicines for Malaria Venture
Medicines for Malaria Venture (MMV) was established in 1999 as a not-for-profit organization created to
discover, develop and deliver safe, effective and affordable antimalarial drugs through effective publicprivate
partnerships. MMV’s vision is a world in which affordable and effective medicines will cure and
protect the millions at risk of malaria and help to ultimately eradicate this terrible disease.
MMV is currently managing the largest–ever portfolio of over 50 antimalarial projects in collaboration with
over 130 pharmaceutical, academic, and endemic-country partners in 44 countries. With its partners, MMV
has recently launched its first ever product – a sweet, paediatric formulation, Coartem® Dispersible. Another
MMV-supported product, Eurartesim™, has been submitted to the EMEA for approval and a third,
Pyramax® is being prepared for submission in 2010. Seven further potential medicines are in clinical
development. The portfolio of discovery projects includes 19 completely new classes of compounds.
With over USD 470 million received and committed from government agencies, private foundations,
international organizations, and corporate foundations; research carried out in the labs and clinical trial sites
of its research partners; and industry partners contributing to the effort with staff, facilities, and technology,
MMV is well set to deliver a range of new medicines. These will be the tip of the spear that, with an array of
other tools and strategies, will finally be capable of eradicating malaria once and for all.

About sanofi-aventis
Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic
solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New
York (NYSE: SNY). For more information, visit: www.sanofi-aventis.com

Bron: en.sanofi-aventis.com/binaries/200911...
flosz
3
Crucell adenovirus-based malaria vaccine candidate
Project Name: Crucell Holland Ltd. Ad35.CS/Ad26.CS Prime Boost
Partner: Crucell N.V.
Development stage: Preclinical; cGMP manufacturing
Platform: Replication-incompetent, recombinant human adenovirus serotype 35 and 26 vectors expressing P. falciparum gene encoding the circumsporozoite (CS) surface antigen
Antigen: Full-length CS gene
Adjuvant: N/A
Recent events: Completed release of Ad26.CS.01 Master Virus Seed and manufacture of Ad26.CS.01 drug substance (clinical trial material). Stability of Ad35.CS.01 drug product continues.
Project Initiation: October 2007
Project End-date: Current agreement with Crucell continues through July 2012. There is no project end-date identified for the clinical trial portion of the project.
___________________________

THE PROJECT: Exploring the effectiveness of a prime-boost approach

The PATH Malaria Vaccine Initiative (MVI) and the United States Agency for International Development (USAID) Malaria Vaccine Development Program (MVDP) are collaborating with the Dutch biopharmaceutical company Crucell N.V. to accelerate the development of a promising type of malaria vaccine. The partners will conduct studies to determine the effectiveness of Crucell’s prime-boost vaccine approach on the malaria parasite Plasmodium falciparum. This approach uses adenoviruses (a type of virus associated with the common cold and other minor respiratory infections) to deliver a malaria antigen to the immune system. The vaccine is made by inserting the gene for the P. falciparum malaria parasite’s circumsporozoite protein (CSP), the only antigen that has proven to be protective in studies, into adenoviral vectors, which act as a delivery vehicle for vaccination.

THE INNOVATION: Using two vectors to boost immune response

The vaccine candidate uses two adenoviral serotypes—Ad35.CS and Ad26.CS—as vectors, or delivery mechanisms. Adenoviruses are recognized as being among the most potent vector systems tested to date in humans and this delivery method may elicit a more potent and comprehensive immune response to the CSP antigen.
The prime component of the vaccine, Ad35.CS, is being tested in a Phase 1 study in partnership with the National Institute of Allergy and Infectious Diseases. The partnership between MVI, Crucell and MVDP will make it possible to clinically develop the Ad26.CS boost component of the vaccine.
Crucell’s AdVac® technology supports the practice of inserting genetic material from the disease-causing virus or parasite into an adenoviral vector that has been altered so that it does not cause disease. The vector then delivers the immunogenic material directly to the immune system. However, if a person has been pre-exposed to the virus (this is common for certain adenovirus types) or previously immunized with an adenovirus-based vaccine, it may be very difficult to enhance the immune response with additional vaccine doses. This novel approach aims to circumvent that problem by immunizing first with one adenovirus (Ad35.CS) and then boosting with a different one (Ad26.CS). Since these particular adenoviruses do not regularly occur in the human population, pre-existing antibody responses should be low, which may help to ensure high immune responses against the malaria parasite.

THE POTENTIAL: Finding an effective vaccine to save lives
Malaria kills one child every 40 seconds and is a major health problem in much of the world, particularly in sub-Saharan Africa. A vaccine is viewed as a critical part of a long-term malaria-control strategy and another invaluable tool in the fight against the disease. Childhood immunization programs, which are among the most cost-effective health interventions, already save the lives of millions of children every year. A safe, effective, and affordable malaria vaccine would have the potential to save even more lives.
Supporting the development of Crucell’s adenovirus-based approach is part of MVI’s strategy to advance an array of vaccine approaches and candidates that have the potential to either halt the malaria parasite or greatly reduce the severity of infection.
www.malariavaccine.org/files/MVI_fact...
[verwijderd]
0
For Malaria: Ad35 vectors appear substantially less potent than Ad5, at least in pre-clinical studies.24
Mogelijk dat daarom Malaria zo traag verloopt? (voor de Ad35 oplossing).

A major concern with the use of human adenoviral vectors for malaria in African was the recognition that levels of anti-vector immunity were particularly high in African populations. For example the prevalence of antibodies to the most widely used and very potent vector Ad5 was reported as 80% and 85% in Southern and west African populations, respectively.20

Also, a non-significant trend towards negative efficacy in the HIV vaccine STEP trial21 also suggested that there might be some safety concern with the widespread used of Ad5 vectors in Africa where HIV is prevalent.

Reassuringly, however, further follow up of the STEP trial cohort and detailed immunological efforts 22,23 all now support the safety of Ad5 vectors.

Yet the potentially impeding effect of anti-vector immunity on vaccine potency remains an issue for malaria, particularly if high level potency is required for efficacy as suggested by the TRAP studies.

One option is to use less prevalent adenoviral vectors such as Ad35, and this option is being pursued by a Crucell-NIH collaboration, but Ad35 vectors appear substantially less potent than Ad5, at least in pre-clinical studies.24

Therefore, the option of using adenoviral vectors of simian origin (Fig. 1) to which humans have much lower levels of anti-vector immunity appeared particularly attractive for malaria.

www.landesbioscience.com/journals/vac...
flosz
3
Vandaar imo de "boost" met Ad26, zie o.a. vorige pagina.

THE INNOVATION: Using two vectors to boost immune response

The vaccine candidate uses two adenoviral serotypes—Ad35.CS and Ad26.CS—as vectors, or delivery mechanisms. Adenoviruses are recognized as being among the most potent vector systems tested to date in humans and this delivery method may elicit a more potent and comprehensive immune response to the CSP antigen.
The prime component of the vaccine, Ad35.CS, is being tested in a Phase 1 study in partnership with the National Institute of Allergy and Infectious Diseases. The partnership between MVI, Crucell and MVDP will make it possible to clinically develop the Ad26.CS boost component of the vaccine.
Crucell’s AdVac® technology supports the practice of inserting genetic material from the disease-causing virus or parasite into an adenoviral vector that has been altered so that it does not cause disease. The vector then delivers the immunogenic material directly to the immune system. However, if a person has been pre-exposed to the virus (this is common for certain adenovirus types) or previously immunized with an adenovirus-based vaccine, it may be very difficult to enhance the immune response with additional vaccine doses. This novel approach aims to circumvent that problem by immunizing first with one adenovirus (Ad35.CS) and then boosting with a different one (Ad26.CS). Since these particular adenoviruses do not regularly occur in the human population, pre-existing antibody responses should be low, which may help to ensure high immune responses against the malaria parasite.
[verwijderd]
0
quote:

flosz schreef:

Vandaar imo de "boost" met Ad26, zie o.a. vorige pagina.
Thanks,

Maar ik niet uit je artikel gehaald, dat de Ad35 vectors:
"appear substantially less potent than Ad5",
(at least in pre-clinical studies).

Tot op heden nog niet gezien en was in de beleving dat Ad35 beter /superieur was aan Ad5.

De booster met Ad26 kan het product verbeteren, maar dat wil nog niet direct impliceren dat de combinatie met Ad26 de te tekortkoming ten opzichte van Ad5 volledig gaat compenseren; laat staan verbeteren.

p.s. bij TB was het resultaat uit phase I natuurlijk wel interessant.
flosz
4
Imo dienen "ze" gewoon samen met GSK spijkers met koppen te slaan. Voor nu gesprekken met GSK afw88. mbt verdere samenwerking....pers. hoop ik op "kannen & kruiken".
z0n0p
0
Lijkt een duivels dilemma. HIV dat Ad5 niet "verdraagt" en malaria dat blijkbaar minder goed gedeit op Ad35. En HIV en malaria zijn de "killers" in afrika.
flosz
5
"The vaccine is designed to overcome the pre-existing immunity in humans against the most commonly used recombinant vaccine vector, adenovirus serotype 5. These encouraging preliminary results are paving the way for the further development of this vaccine vector for HIV and other pathogens." says Dr Barouch.
www.iex.nl/forum/topic.asp?forum=228&...
flosz
3
quote:

MeawandMoo1 schreef:

Tot op heden nog niet gezien en was in de beleving dat Ad35 beter /superieur was aan Ad5.
Uit 2008:
Adenovirus 5 and 35 vectors expressing Plasmodium falciparum circumsporozoite surface protein elicit potent antigen-specific cellular IFN-γ and antibody responses in mice
In the mouse, Ad35 vectors invade DC less efficiently than Ad5.
Falciparum malaria vaccine candidates have been developed using recombinant, replication-deficient serotype 5 and 35 adenoviruses (Ad5, Ad35) encoding the Plasmodium falciparum circumsporozoite surface protein (CSP) (Ad5.CS, Ad35.CS) (Crucell Holland BV, Leiden, The Netherlands). To evaluate the immunogenicity of these constructs, BALB/cJ mice were immunized twice with either Ad5.CS, Ad35.CS, empty Ad5-vector (eAd5), empty Ad35 vector (eAd35), or saline. Another group received the CSP-based RTS,S malaria vaccine formulated in the proprietary Adjuvant System AS01B (GlaxoSmithKline Biologicals, Rixensart, Belgium). Here we report that Ad5.CS, Ad35.CS, and RTS,S/AS01B, elicited both cellular and serologic CSP antigen-specific responses in mice. These adenoviral vectors induce strong malaria-specific immunity and warrant further evaluation.
7 mei 08, 18:36
www.iex.nl/forum/topic.asp?forum=228&...

Uit 2006:
Immunogenicity and Protection of a Recombinant Human Adenovirus Serotype 35-Based Malaria Vaccine against Plasmodium yoelii in Mice

The advantage of rAd35 over rAd5 as a vaccine carrier was demonstrated in experiments performed with mice with or without anti-Ad5 neutralizing activity, wherein the immunogenicity of rAd35 vaccine was maintained while the potency of rAd5 vaccine was abrogated in mice with anti-Ad5 neutralizing activity. This finding confirms our earlier observations with rAd35SIVgag vaccine (3). Importantly, the rAd35PyCS vaccines protected mice both in the presence and in the absence of anti-Ad5 immunity against a high-dose sporozoite challenge in an established rodent challenge model. Since the level of anti-Ad5 neutralizing activity in the mice equaled the levels reported for humans (22), these data suggest that the potency of rAd5 vaccine can be significantly hampered in clinical trials (39), thus warranting Ad serology testing of patients enrolled in clinical trial studies.
iai.asm.org/cgi/content/full/74/1/313

Incl. de samenvatting van Biocon:
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&...

Uit de pubmed-draad.
Evaluation of a prime-boost vaccine schedule with distinct adenovirus vectors against malaria in rhesus monkeys.
Rodríguez A, Mintardjo R, Tax D, Gillissen G, Custers J, Pau MG, Klap J, Santra S, Balachandran H, Letvin NL, Goudsmit J, Radošević K.
Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands.

A vaccine that elicits both specific antibodies and IFN-gamma-producing T cells is required to protect against pre-erythrocytic malaria. Among the most promising approaches to induce such complex immunity are heterologous prime-boost vaccination regimens, in particular ones containing live viral vector. We have demonstrated previously that adenovectors serotype 35 (Ads35) encoding the circumsporozoite (CS) antigen or liver-stage antigen-1 (LSA-1) are highly effective in improving the T-cell responses induced by immunizations with protein-based vaccines in a heterologous prime-boost schedule. Here we evaluated the potential of a heterologous prime-boost vaccination that combines the Ad35.CS vector with the serologically distinct adenovector Ad5.CS, in rhesus macaques, after establishing the potency in mice.
flosz
3
Vervolg.
We show that the heterologous Ad35.CS/Ad5.CS prime-boost regimen elicits both antibody responses and robust IFN-gamma-producing CD8(+) T-cell responses against the CS antigen. Analysis of the quality of the antibody responses in rhesus macaques, using indirect immunofluorescence assay (IFA) with Plasmodium falciparum-coated slides, demonstrated that this heterologous prime-boost regimen elicits a high titer of antibodies that are able to bind to P. falciparum sporozoites. Level of the IFA response was superior to the response measured with sera of an adult human population living in endemic malaria region. In conclusion, the combination of Ad35.CS, a vaccine based on a rare serotype adenovirus, with Ad5.CS or possibly another adenovector of a distinct serotype, induces a complex immune response that is required for protection against malaria, and is thus a highly promising approach for pediatric vaccination.
www.ncbi.nlm.nih.gov/pubmed/19686691
www.iex.nl/forum/topic.asp?forum=228&...
[verwijderd]
0
Toerist in tropenland onnodig ziek

Nederlanders zijn slecht voorbereid op ziektes die ze kunnen oplopen als ze in een ver land zijn. Zo slikken twee op de tien vakantiegangers geen tabletten tegen malaria.

Verder laten vier op de tien zich niet inenten tegen hepatitis-A. Dat blijkt uit onderzoek van het AMC in Amsterdam. De resultaten zijn gepresenteerd op de 40ste editie van de Vakantiebeurs.

Je kan je tijdens de vakantie een hoop narigheid besparen door je goed voor te bereiden. Dat gebeurt te weinig, zeggen de onderzoekers, en daarom gaan er nog steeds Nederlanders dood aan malaria.

www.rtl.nl/(/actueel/rtlnieuws/binnen...

DRW
flosz
2
Published online 20 January 2010 | Nature | doi:10.1038/news.2010.20

GlaxoSmithKline goes public with malaria data
Company to place structures and properties of drug leads in the public domain.
Declan Butler
GlaxoSmithKline is to deposit more than 13,500 structures of possible drugs against malaria into the public domain, along with associated pharmacological data. The move marks the first large-scale public release of such structures by a pharmaceutical company, and it could lead to others following suite.
The news is part of an "open innovation" strategy to be announced today by Andrew Witty, GSK's CEO, at the Council on Foreign Relations in New York. The strategy also includes the creation of an "open lab" based at the company's neglected-diseases research facility at Tres Cantos in Spain, where academic researchers will be able to apply to work and access company expertise and resources.
GSK's move marks the latest development in a trend towards greater access to industry compound libraries — access that was unheard of just a few years ago. Over the past decade, new public-private partnerships such as the Global Alliance for TB Drug Development and the Medicines for Malaria Venture (MMV) have forged deals with drug firms to give them privileged access to the companies' compound libraries.
The GSK move takes this a step further by opening up access to all academic scientists and other companies. "It's a good step," says Tido von Schoen-Angerer, head of the Campaign for Access to Essential Medicines at Médecins Sans Frontières (Doctors without Borders), who says he hopes companies will open their libraries for other diseases.
Exhaustive screen
The structures were identified as inhibiting the malaria parasite Plasmodium falciparum in a screen of the company's 2-million-compound library — a process that took five scientists at Tres Cantos around one year to complete.
"The size of the screening is not earth-shattering news," says Timothy Wells, chief scientific officer of MMV. MMV, which collaborated with GSK on the screen, has, for example, also collaborated with Novartis to screen some 2 million compounds held by the company for activity against the parasite, and found 6,000 candidate 'hits'.
What is news, Wells says, is the public-domain aspect. "It's something everybody in pharma has talked about doing, and everybody seems to have a plan to do it some time in the future, but GSK are the first to really step into the breach and actually do it."
Instead of researchers relying on their own small, isolated and fragmented efforts, the field can now work off and build a shared data set, Wells says. It should also reduce duplication. "We often have academics coming to us and saying we have found a new structure, and we tell them that we already have ten of those," says Wells, "Now all of that data will be in public databases."
What's also important, says Bernard Pécoul, head of the Geneva-based Drugs For Neglected Diseases initiative, is that GSK intend not only to release the structures but also relevant data they hold on the 'druggable properties' of the compounds such as its solubility, absorption, metabolism or toxicological profile, which will help with weeding out compounds which would be dead-ends in terms of drug development. "This is extremely precious information," says Pécoul.
More to come
Janet Morgan, a spokesperson for GSK, says that the company does not intend to host the database of the structures itself but is under discussions with one or more existing databases accessible to scientists. The initial deposition will also likely be mirrored by other databases, as already happens for genome sequences, for example, which are mirrored in GenBank and at the European Bioinformatics Institute.
GSK may screen and publish structures for other neglected diseases for which assays are available. "We'll look at this on a case-by-case basis," Morgan says.
The assay GSK used tested which compounds inhibited the metabolism of the malaria parasite in infected red blood cells. Researchers will next need to also screen the active molecules identified against the other life cycle stages of the parasite, in particular the sexual stages that get transmitted from person to person.

The GSK announcement comes on the heels of the opening on 18 January of ChEMBLdb, a drug discovery database of more than half a million compounds, their targets, and genomic and chemical data. It originally belonged to the Belgian biotech company Galapagos NV but was transferred to the public domain with £4.7 million from the UK Wellcome Trust.
www.nature.com/news/2010/100120/full/...
439 Posts, Pagina: « 1 2 3 4 5 6 ... 14 15 16 17 18 19 20 21 22 » | Laatste
Aantal posts per pagina:  20 50 100 | Omhoog ↑

Meedoen aan de discussie?

Word nu gratis lid of log in met uw e-mailadres en wachtwoord.

Direct naar Forum

Markt vandaag

 AEX
914,27  +3,75  +0,41%  18:05
 Germany40^ 18.707,70 +0,15%
 BEL 20 3.975,74 -0,52%
 Europe50^ 5.039,24 +0,28%
 US30^ 39.428,80 -0,63%
 Nasd100^ 18.852,60 +0,70%
 US500^ 5.320,79 +0,18%
 Japan225^ 38.882,80 +0,63%
 Gold spot 2.349,25 -1,23%
 EUR/USD 1,0830 +0,06%
 WTI 76,90 -0,52%
#/^ Index indications calculated real time, zie disclaimer

Stijgers

VIVORYON THER... +57,13%
HEIJMANS KON +5,42%
BAM +3,81%
ASML +2,61%
ASMI +2,37%

Dalers

Alfen N.V. -4,93%
EBUSCO HOLDING -3,10%
FASTNED -2,88%
JDE PEET'S -2,49%
Philips Konin... -2,29%