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1. ved 11 mei 2006 02:32

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   Adjuvanted Formulation of sanofi pasteur H5N1 Pandemic Influenza Vaccine Candidate Demonstrates Significant Immune Response
   
   Update: 7:18 PM ET May 10, 2006
   
   LYON, France, May 10, 2006 /PRNewswire-FirstCall via COMTEX/ -- A study published online in The Lancet on May 11 demonstrated that multiple dosage formulations of a candidate H5N1 influenza vaccine developed by sanofi pasteur were well- tolerated and generated an immune response, with and without adjuvant. Of the formulations being tested, an alum-adjuvanted 30 microgram dosage generated the most substantive immune response (66.7% HI [haemaggluttination inhibition] seroconversion rate after two vaccinations) and was well-tolerated in the clinical study.
   This is the first trial of an H5N1 pre-pandemic influenza vaccine candidate comparing vaccines with and without adjuvants. A study of a similar, unadjuvanted candidate H5N1 vaccine produced by sanofi pasteur in the U.S. that was published in the New England Journal of Medicine in March required two 90 microgram doses to generate a significant immune response in about 50 percent of trial participants. Because the French and U.S. studies were conducted independently, it is not possible to make direct comparisons of the results. The immune response of the adjuvanted 30 microgram formulation was consistent with requirements of the European Agency for the Evaluation of Medicinal Products (EMEA) for licensure of seasonal influenza vaccine. The French study was sponsored by sanofi pasteur using vaccine produced by the company in France.
   The data will be submitted as part of the company's core vaccine dossier to the EMEA. The core dossier is being developed in strict accordance with EMEA guidelines. This process is expected to reduce the time necessary for approval of a pandemic vaccine in Europe once a strain is identified and a pandemic is declared.
   In subsequent trials, sanofi pasteur will explore different dosages that may be helpful in answering questions about dose-sparing strategies, which are being widely discussed among the public health community. The lower the dosage of a pandemic vaccine, the more doses can be produced and the more people that can be vaccinated should a pandemic occur.
   The vaccine for the study was produced at sanofi pasteur's Marcy L'Etoile facility in France. Follow-up studies, currently being planned, will be performed using vaccine produced at the company's Val de Reuil, France facility, where it will be produced on an industrial scale, which will mimic the manufacturing scale that will be used during a declared pandemic.
   A similar study with a U.S-produced, adjuvanted H5N1 candidate sanofi pasteur vaccine is currently being conducted by the US National Institutes of Health's National Institute for Allergy and Infectious Diseases (NIAID).
   Sanofi pasteur remains committed to global pandemic preparedness and, as part of the company's pandemic program, is also exploring alternative adjuvants that may further enable expansion of capacity.
   The Study Design
   The study published in The Lancet was multi-center, randomised, open-label and non-controlled with 300 healthy, 18 to 40 year-old participants. Each study volunteer received one of six inactivated split influenza A/Vietnam/1194/2004 (H5N1) influenza vaccine formulations. Enrolled subjects were randomly allocated to one of six groups that received 7.5, 15 or 30 microgram of HA (haemmagglutinin), with or without adjuvant. Each subject received two intramuscular injections of the assigned formulation into the deltoid (each subject received two injections of the same formulation). Vaccines were given 21 days apart. Randomization lists were stratified by center and was created using the block method with decreasing block sizes of 18, 12, and 6 so that a similar number of subjects were enrolled into each group at any given time.
   The trial objectives were to describe the safety profile and the immune response 21 days after each vaccination. Subjects attended three trial visits (Day D0, D21 and D42) for vaccination (D0, D21 only), blood sampling and safety data collection. Subjects were kept under observation for 30 minutes after vaccination, and were given safety diaries, digital thermometers and rulers to assess and record adverse events (AEs). For the period D0-D7, diaries included a list of solicited injection site and systemic AEs, including those recommended for the evaluation of interpandemic vaccines by the CHMP.
   All formulations induced an immune response, and responses were detectable in some subjects after only one dose. The adjuvanted 30 microgram formulation induced the greatest response. Adjuvant did not improve the response to the lower doses. Two vaccinations of non-adjuvanted 7.5 microgram, adjuvanted 15 microgram or non-adjuvanted 15 microgram seroconverted >40% of subjects (HI test only). HI and neutralizing results followed similar trends.
   Sanofi Pasteur and Pandemic Preparedness
   Sanofi pasteur, the vaccines business of the sanofi-aventis Group, is committed to global pandemic preparedness. As the world leader in research, development and manufacturing of influenza vaccine, sanofi pasteur is actively involved in other projects in the U.S. and Europe, with the goal of developing a vaccine to protect against a pandemic influenza virus.
   Sanofi pasteur is investing in a major expansion of its influenza vaccine production capacity in the US, and also of its vaccine production capacity in France (Val de Reuil facility).
   In the U.S., sanofi pasteur has a number of pandemic-related agreements with the U.S. government involving development of pandemic vaccine stockpiles, production of investigational doses and the development of cell culture technology, including:
   -- In May 2004, sanofi pasteur contracted with the U.S. National
   Institutes for Allergy and Infectious Diseases (NIAID) to produce
   investigational doses. The doses were shipped to the NIAID in
   March 2005. The studies were completed in 2005 and the results were
   published in New England Journal of Medicine (March 30, 2006).
   
   -- In September 2004, the company signed a contract with HHS to produce
   two million doses of bulk vaccine derived from the H5N1 viral strain.
   The bulk doses were produced and are being stored and can be formulated
   and filled upon government request.
   
   -- In November 2004, the HHS awarded a contract to sanofi pasteur to
   expand and safeguard the egg supply needed to produce influenza vaccine
   and to formulate each year investigational doses for a potential
   pandemic influenza vaccine.
   
   -- In April 2005, the HHS awarded a contract to sanofi pasteur to
   accelerate the development of a cell-culture influenza vaccine in the
   U.S. and to design a U.S.-based cell-culture vaccine manufacturing
   facility.
   
   -- In September 2005, the HHS awarded a contract to sanofi pasteur to
   produce a vaccine to help protect against the H5N1 influenza virus
   strain. The $150 million contract calls for sanofi pasteur to
   manufacture the vaccine in bulk concentrate form at its U.S.
   headquarters in Swiftwater, PA. The agreement provides for additional
   fees to be paid to sanofi pasteur for storage of the vaccine as well as
   for formulation and filling of the vaccine upon government request.
   
   -- In February 2006, sanofi
2. ved 11 mei 2006 02:49

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   vervolg:
   
   -- In February 2006, sanofi pasteur supplied NIAID with
   15,000 investigational doses of H5N1 vaccine formulated with and
   without alum adjuvant for use in NIAID-sponsored clinical studies
   
   In Europe, sanofi pasteur initiated and runs a large range of projects:
   
   -- In France, sanofi pasteur sponsored the first clinical trials of an
   H5N1 influenza vaccine candidate that compared vaccines with and
   without adjuvants (the study in the current online issue of The
   Lancet.)
   
   -- In France, sanofi pasteur was awarded a contract by the French Ministry
   of Health to produce a 1.4 million dose stockpile of the H5N1 candidate
   studied in the above-mentioned trial. By this agreement, the company
   could also provide enough vaccine to protect up to 28 million people in
   France in the event of a pandemic being declared, once the actual virus
   strain responsible is identified.
   
   -- Sanofi pasteur is the only vaccine manufacturer to participate in
   FLUPAN, a European Union (EU) funded collaboration. FLUPAN partners
   include the NIBSC, the University of Reading (UK), Instituto Superiore
   di Sanita (Italy), the Health Protection Agency (UK) and the University
   of Bergen (Norway). FLUPAN is intended to improve the level of
   pandemic preparedness in the EU. Sanofi pasteur is also producing
   another strain with pandemic potential (H7N1) to be used in a FLUPAN
   clinical study.
   
   -- In February 2006, sanofi pasteur provided candidate H5N1 vaccine to the
   Italian Ministry of Health and entered into an agreement to provide an
   actual pandemic strain of vaccine, once a pandemic has been declared.
   
   In Australia:
   
   -- A contract has also been signed with the Australian government for the
   supply of vaccine in the event of a pandemic influenza outbreak.
   
   Influenza Overview
   
   Influenza is a highly contagious virus that is spread easily from person to person, primarily when an infected individual coughs or sneezes. An influenza pandemic is a global epidemic of an especially virulent virus, new for humans, with the potential for severe morbidity and mortality. According to the World Health Organization (WHO), the next pandemic is likely to result in 1 to 2.3 million hospitalizations and 280,000 to 650,000 deaths in industrialized nations alone. Its impact will most likely be even more devastating in developing countries. These reasons have lead many countries to organize national plans against influenza pandemic
   About sanofi-aventis
   The sanofi-aventis Group is the world's third-largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular disease, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. The sanofi-aventis Group is listed in Paris (EURONEXT: SAN) and in New York (SNY : sanofi aventis sponsored adr
   News , chart, profile, more
   Last: 48.03-0.26-0.54%
   
   Sponsored by:
   SNY48.03, -0.26, -0.5%) .
   Sanofi pasteur, the vaccines business of the sanofi-aventis Group, sold more than a billion doses of vaccine in 2005, making it possible to protect more than 500 million people across the globe. The company offers the broadest range of vaccines, providing protection against 20 bacterial and viral diseases. For more information, please visit: www.sanofipasteur.com
   
   Bron:
   
   www.marketwatch.com/News/Story/Story....
   
3. [verwijderd] 11 mei 2006 08:03

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   Art. uit The Lancet:
   
   The Lancet DOI:10.1016/S0140-6736(06)68656-X
   Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial
   
   Jean-Louis Bresson a, Christian Perronne b, Odile Launay c, Catherine Gerdil d, Melanie Saville , John Wood e, Katja Höschler f and Maria C Zambon f
   
   Background Pathogenic avian influenza A virus H5N1 has caused outbreaks in poultry and migratory birds in Asia, Africa, and Europe, and caused disease and death in people. Although person-to-person spread of current H5N1 strains is unlikely, the virus is a potential source of a future influenza pandemic. Our aim was to assess the safety and immunogenicity of a vaccine against the H5N1 strain.
   Methods We did a randomised, open-label, non-controlled phase I trial in 300 volunteers aged 18–40 years and assigned one of six inactivated split influenza A/Vietnam/1194/2004 (H5N1) influenza vaccine formulations, comprising 7·5 μg (with adjuvant n=50, without adjuvant n=49), 15 μg (n=50, n=50), or 30 μg (n=51, n=50) of haemagglutinin with or without aluminium hydroxide adjuvant. Individuals received two vaccinations (on days 0 and 21) and provided blood samples (on days 0, 21, and 42) for analysis by haemagglutination inhibition and microneutralisation. We recorded all adverse events. Analyses were descriptive.
   Findings All formulations were well tolerated, with no serious adverse events, few severe reactions, and no oral temperatures of more than 38°C. All formulations induced an immune response, and responses were detectable in some individuals after only one dose. The adjuvanted 30 μg formulation induced the greatest response (67% haemagglutinin-inhibition seroconversion rate after two vaccinations). Adjuvant did not improve the response to the lower doses. Two vaccinations of non-adjuvanted 7·5 μg, adjuvanted 15 μg, or non-adjuvanted 15 μg seroconverted more than 40% of participants (haemagglutinin-inhibition test only). Haemagglutinin inhibition and neutralising results were comparable.
   Interpretation A two-dose regimen with an adjuvanted 30 μg inactivated H5N1 vaccine was safe and showed an immune response consistent with European regulatory requirements for licensure of seasonal influenza vaccine. We noted encouraging responses with lower doses of antigen that need further study to ascertain their relevance for the choice of the final pandemic vaccine.
   
   Introduction
   Avian influenza H5N1 was originally isolated in birds in China in 1996 and outbreaks were first reported in people and birds in Hong Kong in 1997. The disease is now widespread among poultry and migratory birds in many countries in southeast Asia and has been detected in Africa and several European countries.1 To date (up to April 3, 2006), 190 people have been reported with laboratory-confirmed H5N1 avian influenza, of whom 107 have died.2 The evidence that H5N1 can spread from person-to-person is limited,3 but this subtype represents a potential source of the next influenza pandemic.4 The epidemiological situation, corresponding to pandemic alert step three in the six-step WHO Global Influenza Preparedness Plan, has prompted increased interest in the progress of pandemic vaccine development.5,6
   The yearly availability of influenza vaccines is an example of effective collaboration between health authorities, vaccine manufacturers, and WHO.7 Such collaboration would be pivotal in an influenza pandemic, during which rapid vaccination would limit spread of the disease. The European Committee for Medicinal Products for Human Use (CHMP) has developed guidelines for the fast-track licensing of pandemic influenza vaccines. These recommend developing a mock-up pandemic vaccine to be submitted for regulatory approval in the form of a core pandemic dossier during the interpandemic period.8 Such a vaccine should share several features (such as manufacturing process, antigen content, and adjuvant) with the final intended vaccine.
   Conventional influenza vaccines are unlikely to be suitable against an influenza pandemic caused by a new subtype, such as H5N1, against which the human population has limited or no prior immunity.7 Findings of research suggest that: pandemic vaccines will require an adjuvant system to enhance immunogenicity or to spare antigen content; that two vaccinations will be needed to elicit a satisfactory response; and that avian influenza haemagglutinin will be less immunogenic than human influenza haemagglutinin, or that more sensitive serological methods will be needed to detect human antibodies to avian viruses.7,9–14
   Our aim was to assess the safety and immunogenicity of an H5N1 influenza vaccine based on a reference strain derived by the UK National Institute for Biological Standards and Control (NIBSC) from the pathogenic influenza A/Vietnam/1194/2004 strain isolated from a person with H5N1 influenza.15 Here, we present data from the first part (up to day 42) of a continuing trial.
   
4. [verwijderd] 11 mei 2006 08:04

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   Pasteur, Hôpital Cochin, Paris, and Unité de Maladies Infectieuse et Tropicales, Hôpital Raymond Poincaré, Garches. Our main exclusion criteria were: current febrile illness; immunodeficiency; recent receipt of blood, blood-derived products, or immunosuppressive treatment; current long-term systemic corticosteroid therapy; recent (previous 4 weeks) vaccination or vaccination planned in next month; and pregnancy. A history of travel to H5 endemic areas was not an exclusion criterion, and we did not restrict the travel of participants after enrolment. Our inclusion criteria were age 18–40 years on day of enrolment, provision of written informed consent, ability to attend all scheduled visits and to comply with all trial procedures, entitled to national social security, and registered in the French file of healthy volunteers in clinical trials. Women had to be unable to bear children or able to produce a negative urine pregnancy test, having used an effective method of contraception or been abstinent for at least 4 weeks before the first vaccination (to be continued for at least 4 weeks after the second vaccination).
   The trial protocol and all relevant documents were approved by an ethical review committee (Comité Consultatif de Protection des Personnes dans la Recherche Biomédicale, Paris-Necker), and we notified the French health authority (Agence Française de Sécurité Santaire des Produits de Santé) of the study in accordance with French regulations. All eligible volunteers gave written informed consent before inclusion.
   Procedures
   The H5N1 influenza vaccine was a monovalent A/H5N1, inactivated, split-virion influenza vaccine manufactured by sanofi pasteur (Lyon, France). It was produced on a pilot scale in embryonated hens' eggs, using the licensed manufacturing process for the interpandemic vaccine Vaxigrip as previously described16 and adapted to the particular avian strain, according to biosafety guidelines for the production and quality control of vaccines for use during pandemics of human influenza.17
   The vaccine strain was the influenza A/Vietnam/1194/2004/NIBRG14 (H5N1) reference strain prepared by the NIBSC, and is one of the reference viruses indicated as suitable for use in a mock-up vaccine by the CHMP.8 This modified virus contains modified haemagglutinin and neuraminidase from the highly pathogenic avian strain influenza A/Vietnam/1194/2004 and other viral proteins from influenza A/PR/8/34 (H1N1).15 The haemagglutinin was modified to remove the multibasic aminoacid at the cleavage site. Haemagglutination-inhibition tests confirmed that NIBRG-14 haemagglutinin was antigenically the same as that of the wildtype influenza A/Vietnam/1194/2004 virus. The NIBSC tested for absence of virulence in animal models, including ferrets. We selected the dose range to be assessed based on published experience with other pandemic vaccine candidates.9,10 We prepared prefilled 0·5 mL syringes (23 g 1 inch needle) of 7·5 μg, 15 μg, or 30 μg of haemagglutinin in a phosphate buffered saline solution without adjuvant. The neuramidase content of the vaccine was not measured. The non-adjuvanted formulations were ready to use. We prepared the three aluminium hydroxide-adjuvanted formulations on site (by the bedside) just before use, according to a reconstitution protocol, to contain a final adjuvant content of 600 μg aluminium hydroxide per injected dose: we transferred the total volume of influenza vaccine contained in the prefilled syringe and the total volume of separate prefilled syringes of adjuvant to a sterile vial and mixed for 10 s before drawing the solution into a new syringe (23 g 1 inch needle), gently swirling to homogenise the antigen-adjuvant suspension, and injecting intramuscularly. Three vaccine batches were used: S3977 for the 30 μg, the adjuvanted 30 μg, and the adjuvanted 15 μg formulations; S3976 for the 15 μg and the adjuvanted 7·5 μg formulations; and S3974 for the 7·5 μg formulation. We did a study mimicking on-site formulation of vaccine with adjuvant on the 30 μg, 15 μg, and 7·5 μg adjuvanted formulations; results indicated similar adsorption coefficients. The injected volume was 0·5 mL in all cases, except for the adjuvanted 30 μg formulation for which the volume was 1 mL. Each final dose also contained 45 μg of the preservative thiomersal.
   We randomly allocated participants to one of six groups to receive 7·5 μg, 15 μg, or 30 μg of haemagglutinin, with or without adjuvant. Each participant received two intramuscular injections, 21 days apart, of the assigned formulation into the deltoid. We stratified randomisation lists by centre and created them with the block method, using decreasing block sizes of 18, 12, and six so that a similar number of people was enrolled into each group at any given time. The sequence was generated at sanofi pasteur by a statistician who was not involved in the rest of the trial.
   Our aim was to describe the safety profile of, and immune response to, the vaccine 21 days after each dose. Participants attended three trial visits (on day 0, 21, and 42) for blood sampling, vaccination (day 0 and 21 only), and safety data collection. We kept individuals under observation for 30 min after vaccination, and gave them safety diaries, digital thermometers, and rulers to assess and record adverse events. From days 0 to 7, diaries included a list of solicited injection site and systemic adverse events, including those recommended for the assessment of interpandemic vaccines by the CHMP. The intensity of non-quantifiable reactions—eg, pain—was assessed with a severity scale: mild, noticeable but does not interfere with daily activities; moderate, interferes with daily activities; severe, prevents daily activities. At the next visit (day 21 and 42), we (J-LB, CP, OL, and clinicians at each study site) interviewed patients, transcribed adverse events onto case report forms, and assessed whether unsolicited adverse events were vaccine-related. By convention, we judged all solicited adverse events vaccine-related. We collected blood samples in dry tubes and processed them at each trial centre within 24 h. We then froze and shipped the samples to the Health Protection Agency Centre for Infection, London, UK, for centralised analysis.
   We assayed serum samples obtained from individuals on day 0 (before first vaccination), 21, and 42 at the same time to detect haemagglutination-inhibition activity and neutralising activity against the vaccine seed virus (NIBRG14). Work with this virus was done at containment level 3 after local risk assessment, and in line with Health and Safety Executive guidelines. There was no mention of treatment group on either the samples or the accompanying listing provided to the laboratory—ie, we undertook immunogenicity analyses under blinded conditions.
   We used a previously described modified haemagglutination-inhibition assay, using horse erythrocytes instead of turkey erythrocytes, because of their increased sensitivity for the detection of human antibodies against H5.12 Briefly, we treated sera for 16 h with receptor-destroying enzyme, which was then inactivated by incubation at 56°C. From the initial dilution of one in eight, we undertook two-fold dilutions of the serum samples and incubated with the antigen suspension (4 haemagglutination units/25 μL) for 1 h at room temperature. After adding 25 μ
5. [verwijderd] 11 mei 2006 08:05

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   Statistical analysis
   Our planned sample size of 300—ie, 50 people per group—was chosen in line with European guidelines for yearly influenza vaccine trials.19 Our objectives were to describe the safety profile of, and the immune response to, the vaccine 21 days after each vaccination. We planned no formal statistical hypothesis testing. We did statistical analyses for descriptive purposes only and by intention to treat. We summarised results with point estimates and 95% CIs. We summarised safety data in terms of the number and proportion of individuals who had reactions in each group and use Fisher's exact test to compare groups when relevant. In particular, we assessed the occurrence of the following reactions in the 3 days after vaccination in accordance with guidance for interpandemic vaccines: injection site induration of more than 5 cm for more than 3 days; injection site ecchymosis; body temperature of more than 38·0°C—ie, oral temperature of greater than 37·5°C—for 24 h or more; malaise; and shivering.13 We gave haemagglutinin-inhibition titres below the limit of detection (one in eight) an arbitrary intermediate value of one in four. We transformed titres into log10 titres for the calculation of geometric means and 95% CIs. The haemagglutinin-inhibition endpoints were the geometric mean titre (GMT) at each timepoint, as well as the variables recommended for interpandemic influenza vaccines: post-vaccination seropositivity rate (% with titres ≥32, considered equivalent to ≥40); the post-to-pre-vaccination GMT ratio; and the proportion of people seroconverting or displaying a four-fold titre increase post-vaccination.13 We gave microneutralisation titres below the one in 20 limit of detection a value of one in ten. Endpoints were the GMT at each timepoint and the proportion of people with two-fold and four-fold titre increases. The haemagglutinin-inhibition and microneutralisation titre distributions are described with reverse cumulative distribution curves, and are tested with the non-parametric Kruskal-Wallis test over the six groups.
   Role of the funding source
   sanofi pasteur had a role, through its project team, in study design and monitoring, and in writing of the report. The study sponsor had no role in on-site data collection. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
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   Results
   Of 444 individuals contacted, 300 healthy adults consented to participate and were enrolled and randomised (table 1). All 300 individuals received the two planned vaccinations, attended all visits, completed the study up to day 42, gave three blood samples, and were included in analyses. Mean age per group ranged from 24·1 to 26·1 years, and the male-to-female ratio ranged from 0·8 to 1·9. Each centre recruited 70–120 people.
   
   All six formulations were well tolerated with no reports of serious adverse events between days 0 and 42, severe injection-site pain, or febrile episodes with an oral temperature of more than 38°C. More than half the participants in each group reported at least one solicited reaction during the trial (table 2). Fewer injection-site and systemic reactions arose after the second vaccination than after the first in all six groups (data not shown). Injection-site reactions were more common in the adjuvanted groups than in the non-adjuvanted groups for all three haemagglutinin doses, especially after the second injection (Fisher's exact test comparing pooled results from three adjuvanted groups with pooled results from three non-adjuvanted groups: p=0·0811 [after first injection] and p=0·0196 [after second injection]; table 2). This pattern was not the same for systemic reactions (p=0·5634 and p=0·3321 after first and second injection, respectively). The most frequent reactions were pain, headache, and myalgia. With respect to the CHMP endpoints, within 3 days of vaccination: there was no induration of more than 5 cm lasting more than 3 days; one participant in each of the adjuvanted 7·5 μg and the non-adjuvanted 7·5 μg and 30 μg groups had a fever for at least 24 h with a peak oral temperature of more than 37·5°C; and, after each injection, 0–8% of each group (up to four people per group) had injection site ecchymosis, 2–18% malaise, and 0–10% shivering.
   
   Only seven measurable injection-site reactions were greater than 5 cm, six of which arose in the adjuvanted or non-adjuvanted 30 μg groups (three per group). Five solicited systemic reactions met the definition of severe on at least 1 day: one headache in each of the adjuvanted formulation groups, one headache in the 7·5 μg non-adjuvanted group, and one instance of myalgia in the adjuvanted 15 μg group. We judged most of the spontaneously reported adverse events occurring up to day 21 after vaccination unrelated to vaccination (data not shown). Those judged vaccine-related were seemingly unrelated to concentration of antigen or adjuvant presence or absence: 12% (n=6), 18% (n=9), and 14% (n=7) of patients in the non-adjuvanted 7·5 μg, 15 μg, and 30 μg groups, and 10% (n=5), 12% (n=6), and 14% (n=7) in the adjuvanted 7·5 μg, 15 μg, and 30 μg groups. These adverse events were mainly gastrointestinal symptoms, asthenia, or respiratory symptoms or infections.
   Before vaccination, only two of the 300 participants (one in each of the 30 μg adjuvanted and non-adjuvanted groups) had detectable antibodies against H5N1. One person (30 μg group) had a neutralising titre of 83·6 and a haemagglutinin-inhibition titre of 181; the other (30 μg+aluminium hydroxide group) had a low microneutralising titre of 27 and no clearly detectable haemagglutinin-inhibition antibodies.
   With respect to haemagglutinin inhibition, between 6% and 34% of each group had titres of 32 or more on day 21 (after the first vaccination), the proportion increasing to 28–67% on day 42 (after the second vaccination; table 3). The highest responses were seen after the second vaccination with adjuvanted 30 μg haemagglutinin (figure). Adjuvant did not increase response to lower doses. The 15 μg formulations and the non-adjuvanted 7·5 μg formulation induced similar responses (on day 42: 43–44% per group had titres >32; GMT 17·3–19·6). However, responses were much lower with the adjuvanted 7·5 μg formulation (28%; 10·4). After two doses, all six formulations elicited a GMT ratio of more than 2·5, and all except the adjuvanted 7·5 μg formulation elicited seroconversion in more than 40% of participants (table 3). Only the adjuvanted 30 μg formulation, however, induced a seroconversion rate in excess of 60% after two vaccinations. Participants with detectable titres—ie, 8 or more—tended to have titres of 32 or more (figure): of the 144 individuals (all groups combined) with titres of 8 or more on day 42, 139 had titres of 32 or more, the number dropping to 108 at 64 or more and 78 at 128 or more. Although we did not test the one in 40 dilution, we did calculate the proportion of participants with titres of 40 or more for each group in respect of the CHMP criterion for interpandemic vaccines; the numbers were comparable to the proportion with titres of 32 or more, though slightly lower in some cases—eg, this proportion was 63% in the adjuvanted 30 μg group and 39% in the non-adjuvanted 7·5 μg group.
   
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   Neutralising antibody responses followed a similar pattern to those of haemagglutinin inhibition, and the proportion of individuals with a two-fold rise or greater in microneutralisation titres between days 0 and 42 was comparable with the haemagglutinin-inhibition seroconversion rate described above in each group (table 4). We calculated the correlation between titres by haemagglutinin inhibition and microneutralisation with the Spearman rank correlation co-efficient for all groups combined for day 21 data (R=70%) and for day 42 data (R=77%).
   
   On day 21, between 6% (n=3) and 26% (n=13) of people in each group had detectable antibody titres (≥20). On day 42, the proportion was 22–61%. The highest responses were again noted in the two 30 μg groups, and were higher with adjuvant than without (figure). On day 42, the number of people in the non-adjuvanted 7·5 μg, 15 μg, and 30 μg groups with microneutralisation titres of 40 or more were, respectively, ten of 49, 11 of 50, and 13 of 50; the corresponding numbers in the adjuvanted groups were, eight of 50, nine of 50, and 21 of 51. As with haemagglutinin inhibition, the neutralising response elicited by the non-adjuvanted 7·5 μg formulation was similar to that elicited by the two 15 μg formulations and was higher than that elicited by the adjuvanted 7·5 μg candidate.
   Although the Kruskal-Wallis test of the individual titres over the six groups (figure) confirmed a significant formulation effect on both haemagglutinin inhibition and microneutralisation results, the trends between the individual groups were not significant. The trends and differences noted between dose groups is coherent with a lack of power.
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   Discussion
   The two-dose regimen of the H5N1 influenza vaccine tested was well tolerated and elicited neutralising and haemagglutination-inhibiting antibody responses. Although most participants reported at least one reaction to vaccination, they mainly comprised mild-to-moderate injection-site reactions or headache; there were no febrile episodes with an oral temperature or more than 38°C. Adjuvant did not adversely affect the general safety profile.
   Before vaccination, all but two volunteers were H5N1 naive. This result is comparable to that of Treanor and colleagues,20 who noted that about 97% of individuals were H5N1 naive. Why two people in our study had antibodies against H5N1 is unknown. The individual we were able to contact had no relevant travel history and no contact with poultry, but reported that, over a 6-week period in the summer of 2004, he had been in daily contact with a wild crow and had fed it out of his hand. We reran our analyses, excluding these two individuals, and noted no difference in our interpretation of the overall group response (data not shown).
   After two vaccinations, all six formulations met the CHMP immunogenicity requirements for interpandemic vaccines.19 The non-adjuvanted 7·5 μg formulation and the two 30 μg formulations met one of these requirements after a single dose (GMT ratio >2·5). These results should be interpreted with caution, however, since almost all individuals had undetectable titres at baseline and we thus based the GMT ratio on the use of an arbitrary value of half the detection limit at baseline. The CHMP criteria are defined for the standard haemagglutinin-inhibition method on turkey erythrocytes with a detection limit of one in ten and a seroprotection threshold of one in 40, which is an accepted correlate of protection against human influenza virus. We used a modified haemagglutinin-inhibition method on horse erythrocytes with a detection limit of one in eight and considered a seropositivity threshold of one in 32 to analyse the immune response against an avian influenza strain against which there is no correlate of protection. We obtained comparable results when we considered the number of responders at one in 32 or one in 40 dilutions, although in the case of one in 40 the results are indicative only, since we did not test this dilution.
   A two-dose regimen of 30 μg of haemagglutinin induced the highest response, with adjuvanted vaccine being more immunogenic than the non-adjuvanted vaccine. These findings are in line with previous observations that lend support to the use of an adjuvant and a two-dose regimen.6 Results are less clear with lower antigen-content formulations; no adjuvant effect was seen with 15 μg haemagglutinin, and 7·5 μg haemagglutinin seemed more immunogenic without adjuvant than with. It is noteworthy that the adjuvant content was constant for each formulation, meaning that the adjuvant-to-antigen ratio varied. Furthermore, the injected volume of the adjuvanted 30 μg formulation (1 mL) differed from that of the other formulations (0·5 mL), although whether, how, and to what extent this discrepancy affected the immune response is unknown. The noted dose effect between the 30 μg dose and the lower doses was not apparent between the 15 μg and 7·5 μg formulations. We noted similar trends with both the haemagglutinin-inhibition and the microneutralisation methods of analysis, with good correlation between results of the two assays.
   The immune response to the non-adjuvanted 7·5 μg formulation was comparable to that of the two 15 μg formulations on day 42 (after two vaccinations). The geometric mean haemagglutinin-inhibition and microneutralisation titres elicited by the non-adjuvanted 7·5 μg, 15 μg, and 30 μg formulations in our trial are consistent with the US results with 7·5 μg, 15 μg, and 45 μg haemagglutinin, although the assays were done in different laboratories with different strains. The proportions of haemagglutinin-inhibition antibody response (four-fold increase) are not readily comparable between the two trials because of different initial dilutions and cut-off titres.
   The seroconversion rates in excess of 40% seen by the haemagglutinin-inhibition test after two doses of either of the 15 μg formulations, or of the non-adjuvanted 7·5 μg formulation, are encouraging, although neutralising antibody responses were lower. From a public-health perspective, the challenge of pandemic influenza will be different to that of yearly influenza. Annual influenza vaccination aims primarily to induce an optimum immune response—ie, a seroprotective haemagglutinin-inhibition titre of at least 40—to protect the individual against infection. In a pandemic situation, the aim will be to immunise a maximum number of people to protect them against mortality and severe disease. The level of post-vaccination antibodies needed to achieve this protection is not known. Limited manufacturing capacity implies the need to adopt dose-sparing strategies. The challenge, therefore, is to find the appropriate compromise between individual protection and protection from a population perspective.
   Our two-dose adjuvanted 30 μg inactivated H5N1 pandemic vaccine is safe and immunogenic. We also noted encouraging responses with lower doses of antigen.
   www.thelancet.com/journals/lancet/art...
7. [verwijderd] 11 mei 2006 08:15

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   The Lancet Early Online Publication, 11 May 2006
   
   The Lancet DOI:10.1016/S0140-6736(06)68657-1
   Avian influenza vaccines: what's all the flap?
   Suryaprakash Sambhara Gregory A Poland b
   
   During the 20th century three influenza pandemics took place, including the worst pandemic known in 1918–19 when about 40–50 million people died. We now face a risk of the first pandemic of the 21st century because of the emergence of highly pathogenic avian A/H5N1 influenza viruses. These H5N1 viruses have expanded their geographical distribution across countries in Asia, the Middle East, Africa, and Europe, causing widespread illness and death in domestic and migratory birds, and have diverged into two genetically distinct clades. Furthermore, as of May 5, 2006, 206 laboratory-confirmed cases of human infection have been reported to WHO, with 55% ensuing mortality.1 Most of these human fatalities are because of direct virus transmission from infected birds to human beings, although probable human-to-human transmission has also been reported.2 Vaccines developed in response to this pandemic threat, including vaccines against inactivated split virus or baculovirus-expressed viral haemagglutinin, have so far performed below expectations.3,4 Recently a clinical trial was reported of a vaccine created with a reverse genetics approach to generate a virus that expressed the haemagglutinin and neuraminidase genes from an H5N1 virus, inserted into an egg-adapted vaccine virus strain (A/PR/8/34).5 This non-adjuvanted split-virus vaccine (A/Vietnam/1203/04) resulted in a vaccinee seroconversion rate of 54% after a two-dose regimen at 90 μg per dose—a low level of effectiveness which would severely limit the number of vaccine doses that could be manufactured with existing facilities.6
   In today's Lancet, Jean-Louis Bresson and colleagues7 report the results of a randomised, open-label, non-controlled phase I trial, in which 300 healthy participants aged 18–40 years old received one of six inactivated split H5N1 (A/Vietnam/1194/2004) vaccine formulations (7·5, 15, or 30 μg haemagglutinin, with or without aluminium hydroxide adjuvant). Participants were vaccinated on days 0 and 21, and provided blood samples on days 0, 21, and 42 for assessment by haemagglutination inhibition and microneutralisation assays. Although the analyses were descriptive, the findings suggest the vaccines were well tolerated with few severe reactions. The alum-adjuvanted 30 μg formulation induced the highest response (66·7% haemagglutination inhibition seroconversion rate after two vaccinations). However, it is counterintuitive that the adjuvant was not found to improve the immunogenicity or percentage of seroconversion at lower vaccine doses, and only slightly improved immunogenicity at the 30 μg dose. Further study is thus warranted.
   The results of these two early clinical trials clearly indicate that we still do not have a highly immunogenic vaccine to use against H5N1 influenza. Moreover, we do not know if the antibodies induced by these vaccines would be sufficient to protect individuals in the event of an influenza pandemic. Furthermore a so-called dose-sparing effect, which would allow less vaccine antigen (30 μg per dose as reported by Bresson and colleagues) to be used with an adjuvant, seems to be only a part solution—one that would still limit the number of vaccine doses available, given the existing global manufacturing capacity. There are no published reports so far indicating if the antibodies induced by these clade 1 vaccines cross-react with variant clade 1 viruses. In view of the genetic and antigenic differences in the clade 1 viruses, it is more than likely that the antibodies induced by clade 1 vaccines cross-react poorly, which could further limit options for vaccine stockpiling. The available data from the Centers for Disease Control and Prevention indicate that the clade 1 vaccines may not cross-protect against clade 2 viruses. Hence it seems that an optimum vaccine strategy may need to include immunogenic antigens from both clade 1 and clade 2 viruses. Finally, although the seroconversion rates in immunocompetent vaccinees are available, there are no data from immunocompromised populations, such as infants, young children, and elderly people.
   Consistent with the scientific method, the currently available data suggest that we test additional strategies that use egg or cell-culture-based antigen production, viral-vector delivery systems,8,9 and new adjuvants and formulations that have shown potential in animal models, in human beings, or both,10,11 and consider passive immunisation with human or humanised neutralising antibodies against clades 1 and 2 A/H5N1 viruses, especially for immunocompromised individuals (figure). Important considerations for pandemic vaccine development include optimising prime-boost strategies, cost-effectiveness, ease and speed of manufacture, cross-protection against variant strains by the induction of cross-reactive antibodies and/or T cells, universal vaccines that induce protective antibodies and/or cytotoxic T cells against highly conserved proteins, stockpiling, cold-storage considerations, and the ability to confer protection in populations of all ages. The recently issued guidelines from the US Food and Drug Administration for fast-tracking promising candidates through licensing are very timely.12 Will we be ready in time? History will judge our global efforts.
   
   www.thelancet.com/journals/lancet/art...
8. gogogoo 11 mei 2006 09:13

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   Kan iemand aangeven wat de impact van dit stuk is? Ik kom telkens meer te weten over Boitech maar ben nog steeds een leek.
9. ved 11 mei 2006 11:57

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   quote:

   gogogoo schreef:

   Kan iemand aangeven wat de impact van dit stuk is? Ik kom telkens meer te weten over Boitech maar ben nog steeds een leek.
   

   De uitkomsten van beschreven onderzoek onderstrepen
   dat bij Sanofi hard en succesvol gewerkt wordt aan ontwikkeling en verbetering van influenzavaccins
   
   Over de perspectieven en voortgang op dit gebied bij Sanofi (partner v. Crucell) viel onlangs nogal
   wat onzekerheid en twijfel te bespeuren. Bovendien
   werd enige onvrede over het PR beleid van Sanofi, resp. Crucell in omloop gebracht.
   
   Het lijkt erop dat Sanofi zijn leidende positie nog
   eens versterkt en bevestigt.
   
   
10. gogogoo 11 mei 2006 12:15

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    Bedankt ved!
12. [verwijderd] 11 mei 2006 12:38

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    Aanbevolen ved,dat was even nodig zo'n morele ondersteuning!
    
    RB
13. [verwijderd] 11 mei 2006 19:26

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    quote:

    ved schreef:

    [quote=gogogoo]
    Kan iemand aangeven wat de impact van dit stuk is? Ik kom telkens meer te weten over Boitech maar ben nog steeds een leek.
    [/quote]
    
    De uitkomsten van beschreven onderzoek onderstrepen
    dat bij Sanofi hard en succesvol gewerkt wordt aan ontwikkeling en verbetering van influenzavaccins
    
    Over de perspectieven en voortgang op dit gebied bij Sanofi (partner v. Crucell) viel onlangs nogal
    wat onzekerheid en twijfel te bespeuren. Bovendien
    werd enige onvrede over het PR beleid van Sanofi, resp. Crucell in omloop gebracht.
    
    Het lijkt erop dat Sanofi zijn leidende positie nog
    eens versterkt en bevestigt.
    
    

    Die onzekerheid en onvrede golden het CELL-BASED vaccin van Sanofi/Crucell. Deze nieuwe studies betreffen EGG-BASED vaccins en hebben als zodanig weinig met Crucell vandoen, en nemen dus ook niets van de (lichte) onvrede weg. Sterker nog, ze bevestigen het beeld:
    
    Ik heb nog steeds het gevoel (meer is het niet) dat Sanofi hun egg-based vaccins als prioriteit heeft, daar ze daar nu absolute marktleider in zijn, en heel veel winst mee kunnen maken. Dat willen ze zo lang mogelijk doen. Als de cell-based producten eenmaal op de markt zijn, is het waarschijnlijk over voor de eieren en de kipjes, en voor Sanofi's grootschalige faciliteiten hiervoor.
    
    Hun ingehuurde, superieure Crucell-technologie staat een beetje op de backburner, te wachten totdat de cell-based concurrentie serieus aan de weg timmert en producten klaar heeft.
    
    M.a.w. Sanofi/Crucell (cell-based) is de grootste concurrent voor Sanofi (egg-based).
    
    Nogmaals, het is een gevoel. Sanofi werkt aan cell-based, maar niet zo hard als ze zouden kunnen. Als je kijkt naar de harde cijfers, d.w.z. de start van clinical trials, liggen ze gewoon achter wat betreft cell-based vaccins (Vergelijk dat eens met Sanofi's tig clinical trials voor egg-based, zoals die in dit draadje, die zich in een hoog tempo opvolgen!).
    Het zou best kunnen dat ze betreffende andere aspecten van cell-based vaccin ontwikkeling, bv. massa-productie in 20.000 liter vaten, voor liggen op de concurrentie, maar dat is moeilijker objectief te controleren.
14. ved 11 mei 2006 20:09

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    quote:

    maxen schreef:

    Die onzekerheid en onvrede golden het CELL-BASED vaccin van Sanofi/Crucell. Deze nieuwe studies betreffen EGG-BASED vaccins en hebben als zodanig weinig met Crucell vandoen, en nemen dus ook niets van de (lichte) onvrede weg. Sterker nog, ze bevestigen het beeld:
    
    Ik heb nog steeds het gevoel (meer is het niet) dat Sanofi hun egg-based vaccins als prioriteit heeft, daar ze daar nu absolute marktleider in zijn, en heel veel winst mee kunnen maken. Dat willen ze zo lang mogelijk doen. Als de cell-based producten eenmaal op de markt zijn, is het waarschijnlijk over voor de eieren en de kipjes, en voor Sanofi's grootschalige faciliteiten hiervoor.
    
    Hun ingehuurde, superieure Crucell-technologie staat een beetje op de backburner, te wachten totdat de cell-based concurrentie serieus aan de weg timmert en producten klaar heeft.
    
    M.a.w. Sanofi/Crucell (cell-based) is de grootste concurrent voor Sanofi (egg-based).
    
    Nogmaals, het is een gevoel. Sanofi werkt aan cell-based, maar niet zo hard als ze zouden kunnen. Als je kijkt naar de harde cijfers, d.w.z. de start van clinical trials, liggen ze gewoon achter wat betreft cell-based vaccins (Vergelijk dat eens met Sanofi's tig clinical trials voor egg-based, zoals die in dit draadje, die zich in een hoog tempo opvolgen!).
    Het zou best kunnen dat ze betreffende andere aspecten van cell-based vaccin ontwikkeling, bv. massa-productie in 20.000 liter vaten, voor liggen op de concurrentie, maar dat is moeilijker objectief te controleren.
    

    Hallo Maxen,
    
    In deze overwegingen/gevoelens kan ik me zeker verplaatsen. Wat jij beschrijft speelt zeker mee.
    Het blijft natuurlijk wat speculeren want ons zicht
    op wat zich achter de schermen afspeelt is beperkt.
    
    Sanofi, mag je aannemen, weet heel goed hoe de vlag er voorstaat. Bij de recente ronde van HHScontracts en de daaraan tengrondslag liggende beleidsplannen (http://grants.nih.gov/grants/guide/rfa-files/RFA-CI-06-009.html) is wel komen vast te staan dat van die kant vol ingezet gaat worden op overgang naar cell-based vaccines. Dat is Sanofi niet ontgaan en
    mijn inschatting is dat ze niet anders kunnen dan hun eigen strategie hierop afstemmen. Ze zullen wel moeten willen ze hun leidende positie niet verspelen en daarom denk ik dat ze de gelegenheid van de Lancetpublicatie van de succesvolle tests hebben aangegrepen om zich nadrukkelijk te presenteren en te (her)positioneren.
    
15. [verwijderd] 11 mei 2006 22:00

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    Maxen en Ved:
    
    Het hele gebeuren rond dit onderwerp heeft iets dualistisch. Ik weet dat er enkele forumleden, net als ik werkzaam zijn in research en development:
    
    Aan de ene kant wil je de concurrentie helemaal niet laten weten hoe ver je al bent in de ontwikkeling van je nieuwe producten.
    
    Aan de andere kant wil je de autoriteiten ervan overtuigen dat jouw technologie niet alleen de beste is maar ook nog eens snel beschikbaar komt.
    
    Probeer daar maar eens uit te komen.
    
    En dan zijn er nog van die lollige aandeelhouders die alles maar dan ook alles willen weten en lieft gisteren.
    
    Neemt u van mij aan dat er achter de schermen veel meer gebeurt dan waar u en ik van mogen weten !
    En dus dat het opschalingsproject in de USA van Sanofi veel verder is dan wij mogen - met de nadruk op mogen - geloven.
    
    En dan nu het dualistische voor ons als aandeelhouders: aan de ene kant willen wij dat Crucell samen met Sanofi de race wint en aan de andere kant willen we dat de concurrentie daarvan nog niet overtuigd mag zijn.
    
    Kortom: Alles sal reg kom, maar zeker niet via (te) vroege PB's van of Crucell of Sanofi.
    
    Giraf
    
    
16. gogogoo 11 mei 2006 22:22

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    Sanofi-Aventis To Submit BF Data - BW*
    by: MOZGI99 (?/M/a desert island)
    Long-Term Sentiment: Strong Buy 05/11/06 11:43 am
    Msg: 25940 of 25947
    
    The Associated Press/NEW YORK
    Businessweek.com
    
    Sanofi-Aventis to submit bird flu data
    
    MAY. 11 9:08 A.M. ET French drug maker Sanofi-Aventis SA said Thursday that its vaccine unit Sanofi Pasteur will submit study data to European regulators on the immune response to its new bird flu vaccine candidate.
    
    The company said a 30 microgram dose of its vaccine for H5N1 avian flu, combined with alum, was the most effective, with about 67 percent of participants generating an immune response to the vaccine. Sanofi Pasteur said the data will be part of a dossier it will present to the European Agency for the Evaluation of Medicinal Products to speed a product to market.
    
    Sanofi-Aventis said it is conducting a similar study in the United States with the National Institutes of Health's National Institute for Allergy and Infectious Diseases
    
    American depositary shares of Sanofi-Aventis rose 71 cents to $48.74 in premarket activity on the INET electronic exchange.
    
    it seems...
    piece by piece...
    Bush could save his legacy by preparing US citizens like he hunts oil,
    30 Billion to win this war now,
    50 Billion when it comes knocking...
    
    but,
    just a joe schmoe,
    what do i know?
    
    constant forward progression,
    mirroring constant progression of fear and truth closing in on time.
    
    truth is scarier than fiction,
    
    mozgi
17. ved 11 mei 2006 23:19

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    quote:

    giraf+4 schreef:

    ...En dan zijn er nog van die lollige aandeelhouders die alles maar dan ook alles willen weten en liefs; gisteren.....
    

    Wat U zegt Giraf,
    'k zou het niet beter kunnen zeggen; ook overigens een juiste beoordeling dunkt me.
    
    
18. [verwijderd] 12 mei 2006 22:32

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    Onderstaand commentaar op o.a. het artikel in The Lancet vond ik wel zinnig:
    
    Thursday, May 11, 2006
    
    Mixed news on vaccine front
    
    Mixed news from vaccine land. A new vaccine trial reported in today's Lancet produced potential protection in 66% of a small number of subjects using two doses of 30 mg each, 21 days apart. The lowest dose of 7.5 mg still produced what might be an adequate response in 40%.
    
    These results are not terrific, but much better than the previous vaccine trials where much higher doses were needed for comparable responses.
    
    The Sanofi-Pasteur trial in France used an alum adjuvant and whole virus, although the alum was only effective at the higher doses. This was a Phase I clinical trial designed to test the safety of the vaccine. More trials with it are needed to evaluate its effectiveness. These are preliminary data in that regard. If H5N1 develops into a pandemic strain, the amount of protection from this particular non-pandemic strain is unknown. Recent computer models suggest that protection below 50% still might have significant effects on rate of disease spread, so stockpiling even a mismatched H5N1 vaccine is under consideration.
    
    On the bad news side, Helen Branswell of Canadian Press (whose sources are the best) is reporting vaccine makers are worried that
    
    making an H5N1 vaccine is a more difficult job
    
    than they thought, and it was already a formidable job. Early trials required far more of the hemagglutinin protein than seasonal flu vaccines to achieve protection. To compound the difficulty, vaccine makers are finding the amount of hemagglutinin produced by the vaccine seed strains of H5N1 is half or less that produced by usual flu strains. Branswell quotes retired vaccine executive David Fedson to the effect that at current world capacity we could vaccinate only 75 to 100 million people in six months. Ramping up productive capacity is a separate problem from having an effective vaccine. Currently the world has only a fraction of what it would need.
    
    Vaccine makers are not sure why viral antigen yields are so low. Word is that the low yield affects all the current candidate seed strains both in egg-based production and cell culture. These strains have been engineered to grow in eggs or mammalian cells and something about this process seems to have decreased the amount of hemagglutinin they produce. The original ("wildtype") virus makes abundant hemagglutinin, so it isn't a characteristic of the subtype. But the wildtype can't be grown in eggs and growing them in cell culture under ordinary production conditions is too dangerous.
    
    So the news is of two kinds: not horrible and not good.
    
    effectmeasure.blogspot.com/
    
    
19. gogogoo 13 mei 2006 14:18

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    De conclusie "So the news is of two kinds: not horrible and not good." is nogal misleidend.
    
    Het nieuws van Sanofi vind ik 'encouraging' omdat de resultaten stukken beter zijn dan de resultaten to nu toe.
    
    Het algemene nieuws dat het maken van een vaccin wel eens moeilijker kan zijn dan gedacht en dat er capaciteitsproblemen zijn is natuurlijk niet goed....maar of het nieuws is.
    
20. [verwijderd] 13 mei 2006 18:05

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    quote:

    gogogoo schreef:

    De conclusie "So the news is of two kinds: not horrible and not good." is nogal misleidend.
    
    Het nieuws van Sanofi vind ik 'encouraging' omdat de resultaten stukken beter zijn dan de resultaten to nu toe.
    
    Het algemene nieuws dat het maken van een vaccin wel eens moeilijker kan zijn dan gedacht en dat er capaciteitsproblemen zijn is natuurlijk niet goed....maar of het nieuws is.
    
    

    gogogoo
    
    Ik vind dat laatste eigenlijk wel goed. Want als ieder zich zelfrespecterende bio tent zijn eigen variant van een h%N1 vaccin zou kunnen maken dan kan de spoeling wel eens heel erg udn worden.
    Nu kunnen we uitgaan van de kracht van de combinatie Sanofi- Crucell en dat kan wel eens erg goed uitpakken voor deze jongens.
    
    Dus goed nieuws, ik zeg altijd - in mijn vak - het kan niet moeilijk genoeg worden - des te minder concurrentie ! Commodities trading kan iedereen.
    
    Giraf
    
21. gogogoo 13 mei 2006 23:15

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    quote:

    giraf+4 schreef:

    [quote=gogogoo]
    De conclusie "So the news is of two kinds: not horrible and not good." is nogal misleidend.
    
    Het nieuws van Sanofi vind ik 'encouraging' omdat de resultaten stukken beter zijn dan de resultaten to nu toe.
    
    Het algemene nieuws dat het maken van een vaccin wel eens moeilijker kan zijn dan gedacht en dat er capaciteitsproblemen zijn is natuurlijk niet goed....maar of het nieuws is.
    
    [/quote]
    
    gogogoo
    
    Ik vind dat laatste eigenlijk wel goed. Want als ieder zich zelfrespecterende bio tent zijn eigen variant van een h%N1 vaccin zou kunnen maken dan kan de spoeling wel eens heel erg udn worden.
    Nu kunnen we uitgaan van de kracht van de combinatie Sanofi- Crucell en dat kan wel eens erg goed uitpakken voor deze jongens.
    
    Dus goed nieuws, ik zeg altijd - in mijn vak - het kan niet moeilijk genoeg worden - des te minder concurrentie ! Commodities trading kan iedereen.
    
    Giraf
    
    

    Zo kun je het ook bekijken.
    
    Ik bedoel eigenlijk niet goed voor de mensheid.
    Maar als Sanofi met Crucell het eerste is vind ik dat natuurlijk niet erg.