Re: EU-funded flu-research
sorry, the correct link is:
http://ec.europa.eu/research/health/influenza/projects_en.html
see also:
http://en.wikipedia.org/wiki/Flu_research
Flu research
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Flu
Flu
Flu season
Flu vaccine
Flu treatment
Avian flu
H5N1 flu
Flu research
Genome project
Flu research includes molecular virology, pathogenesis, host immune responses, genomics, and epidemiology. These help in developing influenza countermeasures such as vaccines, therapies and diagnostic tools.
The potential H5N1 pandemic has motivated a huge increase in flu research. At least 12 companies and 17 governments are developing pre-pandemic influenza vaccines in 28 different clinical trials that, if successful, could turn a deadly pandemic infection into a nondeadly pandemic infection. A vaccine that could prevent any illness at all from the not-yet-existing pandemic influenza strain will take at least three months from the virus's emergence until full-scale vaccine production could begin; with vaccine production hoped to increase until one billion doses are produced by one year after the virus is first identified.[1]
Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. Solutions to limitations in current vaccine methods are being researched.
The Influenza Genome Sequencing Project is creating a library of influenza sequences that will help us understand what makes one strain more lethal than another, what genetic determinants most affect immunogenicity, and how the virus evolves over time.
Contents [hide]
1 Current major flu research contracts
2 Vaccines
2.1 Live Attenuated Influenza Vaccine
2.2 Reverse genetics
2.3 Cell culture
2.4 Pandemic flu vaccine planning
2.5 H5N1 vaccine research
2.6 H5N1 vaccine approval and stockpiling
3 Anti-viral drugs
4 Spanish flu research
4.1 Blood plasma as an effective treatment
5 Sources and notes
6 See also
7 References
8 Further reading
[edit] Current major flu research contracts
The US federal government on May 4, 2006 awarded five-year contracts for "more than $1 billion to five drug manufacturers developing technology for speedier mass production of vaccines in the event of a pandemic" from the $3.8 billion pandemic preparedness bill passed in 2005. "The federal government says its goal is to be able to distribute a vaccine to every American within six months of a pandemic. Currently, flu vaccines are produced in specialized chicken eggs, but that technique does not allow for speedy mass vaccinations." The companies receiving the contracts were:
GlaxoSmithKline $274.8 million
MedImmune Inc $169.5 million
Novartis Vaccines and Diagnostics $220.5 million
DynPort Vaccine Company,LLC $41 million
Solvay Pharmaceuticals $298.6 million[2]
The US government has purchased from Sanofi Pasteur and Chiron Corporation several million doses of vaccine meant to be use in case of an influenza pandemic from H5N1 and is conducting clinical trials on them. [3] ABC News reported on April 1, 2006 that "Beginning in late 1997, the human trials have tested 30 different vaccines, all pegged to the H5N1 virus." [4]
"To address the H9N2 threat, NIAID contracted with Chiron Corporation to produce investigational batches of an inactivated vaccine, which will be evaluated clinically by NIAID early next year. For H5N1, Aventis-Pasteur, Inc. and Chiron are both producing investigational lots of inactivated H5N1 vaccine preparations; additionally, DHHS has contracted with Aventis to produce up to 2 million doses to be stockpiled for emergency use, if needed, to vaccinate health workers, researchers, and, if indicated, the public in affected areas. Development and evaluation of a combination antiviral regimen against these potential pandemic influenza strains are also now under way." [5]
[edit] Vaccines
A vaccine probably would not be available in the initial stages of population infection [6]. Once a potential virus is identified, it normally takes at least several months before a vaccine becomes widely available, as it must be developed, tested and authorized. The capability to produce vaccines varies widely from country to country; in fact, only 15 countries are listed as "Influenza vaccine manufacturers" according to the World Health Organization [7]. It is estimated that, in a best scenario situation, 750 million doses could be produced each year, whereas it is likely that each individual would need two doses of the vaccine in order to become inmuno-competent. Distribution to and inside countries would probably be problematic [8]. Several countries, however, have well-developed plans for producing large quantities of vaccine. For example, Canadian health authorities say that they are developing the capacity to produce 32 million doses within four months, enough vaccine to inoculate every person in the country. [9]
There are two serious technical problems associated with the development of a vaccine against H5N1. The first problem is this: seasonal influenza vaccines require a single injection of 15 μg haemagluttinin in order to give protection; H5 seems to evoke only a weak immune response and a large multicentre trial found that two injections of 90 µg H5 given 28 days apart provided protection in only 54% of people (Treanor 2006). Even if it is considered that 54% is an acceptable level of protection, the world is currently capable of producing only 900 million doses at a strength of 15 μg (assuming that all production were immediately converted to manufacturing H5 vaccine); if two injections of 90 μg are needed then this capacity drops to only 70 million (Poland 2006). Trials using adjuvants such as alum or MF59 to try and lower the dose of vaccine are urgently needed. The second problem is this: there are two circulating clades of virus, clade 1 is the virus originally isolated in Vietnam, clade 2 is the virus isolated in Indonesia. Current vaccine research is focussed on clade 1 viruses, but the clade 2 virus is antigenically distinct and a clade 1 vaccine will probably not protect against a pandemic caused by clade 2 virus.
[edit] Live Attenuated Influenza Vaccine
In June 2007, the National Institutes of Health (NIH) began enrolling participants in a Phase 1 H5N1 study of an intranasal influenza vaccine candidate based on MedImmune's live, attenuated vaccine technology.[10]
[edit] Reverse genetics
Avian Flu vaccine development by Reverse genetics techniques. Courtesy: National Institute of Allergy and Infectious DiseasesA technique called reverse genetics allows scientists to manipulate the genomes of influenza viruses and to transfer genes between viral strains. The technique allows the rapid generation of seed viruses for vaccine candidates that exactly match the anticipated epidemic strain. By removing or modifying certain virulence genes, reverse genetics also can be used to convert highly pathogenic influenza viruses into vaccine candidates that are safer for vaccine manufacturers to handle.
[edit] Cell culture
Another technique is use of cell cultures to grow vaccine strains; such as genetically engineering baculovirus to express a gene that encodes an influenza coat protein such as hemagglutinin or neuraminidase. "A recent NIAID-supported Phase II clinical trial of a vaccine produced by Protein Sciences Corporation using this strategy showed that it is well tolerated and immunogenic; the company is conducting further clinical evaluation of this product. Other new pathways for producing influenza vaccines include DNA-based approaches and the development of broadly protective vaccines based on influenza virus proteins that are shared by multiple strains." [5]
AVI Bio Pharma Inc. has evidence of inhibition of multiple subtypes of influenza A virus in cell culture with Morpholino oligomers from the results of their labs and four independent research laboratories. "The key finding here is that our NEUGENE(R) therapeutics continue to show efficacy against all strains of influenza A, including H5N1." [11][12]
"Several companies are focusing on new vehicles for growing antigens, which are the bits of a virus or bacterium needed to spur a person's immune system to fight an infection. VaxInnate, a New Jersey-based biotechnology company, has reported success using E. coli bacteria, which can cause a sometimes-fatal infection but also can be used to grow vaccine ingredients when the harmful part of the bacterium is removed. Dowpharma, a unit of Dow Chemical Co, has been using different bacteria found in soil and water, P. fluorescens, which may make a higher volume of antigens more quickly than E. coli." [13] A recent study has shown promise by a vaccine called FluBlOk, which is made in insect cells. This experimental vaccine, which focuses on hemagglutinin, would cut the production process by one to two months, as well as avoiding other pitfalls of chicken eggs.[14]
"The Committee for Medicinal Products for Human Use (CHMP), which reviews applications for 27 EU countries, found that Novartis's Optaflu vaccine, given to more than 3,400 people during clinical studies, met the CHMP's immunogenicity criteria [...] Novartis has said that Optaflu is a subunit vaccine, meaning it contains individual viral proteins rather than whole virus particles. [...] Novartis said it anticipates applying for US licensing of its cell-based flu vaccine in 2008. The company has conducted phase 1 and 2 clinical trials of the vaccine in the United States and in July 2006 announced it would build a $600 million plant in Holly Springs, N.C., to make cell-culture flu vaccines. In May 2006 the US Department of Health and Human Services awarded Novartis a $220 million contract to develop cell-based flu vaccines, and Novartis has said the money would go toward the cost of the new facility. Depending on when its vaccine is approved by the Food and Drug Administration, the plant could begin production as early as 2011 and be ready for full production as early as 2012, with an annual output of 50 million doses of a trivalent vaccine, the company has said. In the event of a flu pandemic, the facility is designed to have the capacity to make up to 150 million monovalent (single strain) doses each year within 6 months of a pandemic declaration, Novartis said. Novartis' other cell-based vaccine production facility is in Marburg, Germany."[15]
[edit] Pandemic flu vaccine planning
According to the US HHS (United States Department of Health & Human Services) Pandemic Influenza Plan Appendix F: Current HHS Activities last revised on November 8, 2005 [16]:
Currently, influenza vaccine for the annual, seasonal influenza program comes from four manufacturers. However, only a single manufacturer produces the annual vaccine entirely within the U.S. Thus, if a pandemic occurred and existing U.S.-based influenza vaccine manufacturing capacity was completely diverted to producing a pandemic vaccine, supply would be severely limited. Moreover, because the annual influenza manufacturing process takes place during most of the year, the time and capacity to produce vaccine against potential pandemic viruses for a stockpile, while continuing annual influenza vaccine production, is limited. Since supply will be limited, it is critical for HHS to be able to direct vaccine distribution in accordance with predefined groups (see Appendix D); HHS will ensure the building of capacity and will engage states in a discussion about the purchase and distribution of pandemic influenza vaccine.
Vaccine production capacity: The protective immune response generated by current influenza vaccines is largely based on viral hemagglutinin (HA) and neuraminidase (NA) antigens in the vaccine. As a consequence, the basis of influenza vaccine manufacturing is growing massive quantities of virus in order to have sufficient amounts of these protein antigens to stimulate immune responses. Influenza vaccines used in the United States and around world are manufactured by growing virus in fertilized hens’ eggs, a commercial process that has been in place for decades. To achieve current vaccine production targets millions of 11-day old fertilized eggs must be available every day of production.
In the near term, further expansion of these systems will provide additional capacity for the U.S.-based production of both seasonal and pandemic vaccines, however, the surge capacity that will be needed for a pandemic response cannot be met by egg-based vaccine production alone, as it is impractical to develop a system that depends on hundreds of millions of 11-day old specialized eggs on a standby basis. In addition, because a pandemic could result from an avian influenza strain that is lethal to chickens, it is impossible to ensure that eggs will be available to produce vaccine when needed.
In contrast, cell culture manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines (e.g., polio vaccine, measles-mumps-rubella vaccine, chickenpox vaccine). In this system, viruses are grown in closed systems such as bioreactors containing large numbers of cells in growth media rather than eggs. The surge capacity afforded by cell-based technology is insensitive to seasons and can be adjusted to vaccine demand, as capacity can be increased or decreased by the number of bioreactors or the volume used within a bioreactor. In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States.
Dose-sparing technologies. Current U.S.-licensed vaccines stimulate an immune response based on the quantity of HA (hemagglutinin) antigen included in the dose. Methods to stimulate a strong immune response using less HA antigen are being studied in H5N1 and H9N2 vaccine trials. These include changing the mode of delivery from intramuscular to intradermal and the addition of immune-enhancing adjuvant to the vaccine formulation. Additionally, HHS is soliciting contract proposals from manufacturers of vaccines, adjuvants, and medical devices for the development and licensure of influenza vaccines that will provide dose-sparing alternative strategies.
[edit] H5N1 vaccine research
See also: H5N1 clinical trials
H5N1
Influenza A virus subtype H5N1
Genetic structure
Infection
Human mortality
Global spread
in 2006
Social impact
Pandemic
WHO pandemic phases
Low risk
New virus
Self limiting
Person to person
Epidemic exists
Pandemic exists
Model of H5N1 virusThere are several H5N1 vaccines for several of the avian H5N1 varieties. H5N1 continually mutates rendering them, so far for humans, of little use. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Dr. Daniel Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine." However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.
Problems with H5N1 vaccine production include:
lack of overall production capacity
lack of surge production capacity (it is impractical to develop a system that depends on hundreds of millions of 11-day old specialized eggs on a standby basis)
the pandemic H5N1 might be lethal to chickens
Cell culture (cell-based) manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines and thereby solve the problems associated with creating flu vaccines using chicken eggs as is currently done. Researchers at the University of Pittsburgh have had success with a genetically engineered vaccine that took only a month to make and completely protected chickens from the highly pathogenic H5N1 virus. [17]
According to the United States Department of Health & Human Services:
In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. Dose-sparing technologies. Current U.S.-licensed vaccines stimulate an immune response based on the quantity of HA (hemagglutinin) antigen included in the dose. Methods to stimulate a strong immune response using less HA antigen are being studied in H5N1 and H9N2 vaccine trials. These include changing the mode of delivery from intramuscular to intradermal and the addition of immune-enhancing adjuvant to the vaccine formulation. Additionally, HHS is soliciting contract proposals from manufacturers of vaccines, adjuvants, and medical devices for the development and licensure of influenza vaccines that will provide dose-sparing alternative strategies. [18]
Chiron Corporation is now recertified and under contract with the National Institutes of Health to produce 8,000-10,000 investigational doses of Avian Flu (H5N1) vaccine. Aventis Pasteur is under similar contract.[3] The United States government hopes to obtain enough vaccine in 2006 to treat 4 million people. However, it is unclear whether this vaccine would be effective against a hypothetical mutated strain that would be easily transmitted through human populations, and the shelflife of stockpiled doses has yet to be determined. [19]
The New England Journal of Medicine reported on March 30, 2006 on one of dozens of vaccine studies currently being conducted. The Treanor et al. study was on vaccine produced from the human isolate (A/Vietnam/1203/2004 H5N1) of a virulent clade 1 influenza A (H5N1) virus with the use of a plasmid rescue system, with only the hemagglutinin and neuraminidase genes expressed and administered without adjuvant. "The rest of the genes were derived from an avirulent egg-adapted influenza A/PR/8/34 strain. The hemagglutinin gene was further modified to replace six basic amino acids associated with high pathogenicity in birds at the cleavage site between hemagglutinin 1 and hemagglutinin 2. Immunogenicity was assessed by microneutralization and hemagglutination-inhibition assays with the use of the vaccine virus, although a subgroup of samples were tested with the use of the wild-type influenza A/Vietnam/1203/2004 (H5N1) virus." The results of this study combined with others scheduled to be completed by Spring 2007 is hoped will provide a highly immunogenic vaccine that is cross-protective against heterologous influenza strains. [20]
[edit] H5N1 vaccine approval and stockpiling
On April 17, 2007, the first US approval for H5N1 flu vaccine for humans was given. This vaccine made by Sanofi-Aventis at a plant in Swiftwater, Pennsylvania is not to be sold commercially; instead the US is stockpiling it as an interim measure while better vaccines are being researched. Two injections given 28 days apart gave evidence of providing protection for 45 percent of the people who got the vaccine in a study. "The U.S. Department of Health and Human Services said it had already purchased 13 million doses of the Sanofi vaccine, enough to inoculate 6.5 million people. The vaccine was approved for people age 18 to 64. Studies in other age groups are ongoing. The most common side effects reported were pain at the injection site, headache, general ill feeling and muscle pain, the FDA said."[21]
This April 17, 2007 "approval by the Food and Drug Administration means the vaccine is no longer considered experimental and therefore could be dispensed during a pandemic without requiring each recipient to sign a form giving informed consent. [...] The two injections combined contain 180 micrograms of antigen, the piece of the H5N1 virus designed to spur immunity. By contrast, a conventional flu shot contains 45 micrograms of antigen: 15 micrograms for each of the three strains it protects against."[22]
The vaccine approved on April 17, 2007 "is based on an H5N1 virus isolated from a Vietnamese patient in 2004. Today's approval by the FDA follows a Feb 27 recommendation by an FDA advisory panel, which found that the vaccine was safe and effective. However, some of the panel members had reservations about the immunogenicity of the vaccine, which in data submitted to the panel was somewhat lower than previously reported in a 2006 article in the New England Journal of Medicine. In a clinical trial, two 90-microgram (mcg) doses of the vaccine, administered to 103 healthy adults 28 days apart, generated a protective immune response in 45% of recipients, the FDA noted. (The researchers used a neutralizing antibody titer of 1:40, a fourfold or more increase in antibody titer, to define adequate immune response.) [...] The national stockpile currently contains 13 million doses of the H5N1 vaccine, enough to vaccinate 6.5 million people [...] HHS has said it is moving forward with the development of a "clade 2" H5N1 vaccine, based on viruses that circulated in birds in China and Indonesia in 2003-04 and spread to the Middle East, Europe, and Africa in 2005 and 2006."[23]
[edit] Anti-viral drugs
Many nations, as well as the World Health Organization, are working to stockpile anti-viral drugs in preparation for a possible pandemic. Oseltamivir (trade name Tamiflu) is the most commonly sought drug, since it is available in pill form. Zanamivir (trade name Relenza) is also considered for use, but it must be inhaled. Other anti-viral drugs are less likely to be effective against pandemic influenza.
Both Tamiflu and Relenza are in short supply, and production capabilities are limited in the medium term. Some doctors say that co-administration of Tamiflu with probenecid could double supplies. [24]
There also is the potential of viruses to evolve drug resistance. Some H5N1-infected persons treated with oseltamivir have developed resistant strains of that virus.
Peramivir is a pharmaceutical drug used to viral infections. Like zanamivir and oseltamivir, peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells. Experimental data indicate that peramivir may have useful activity against many viruses of interest, including H5N1 (avian bird flu) ,hepatitis B, polio, measles and smallpox. HHS Secretary Mike Leavitt announced on January 4, 2007 that the Department has awarded a $102.6 million, four-year contract to BioCryst Pharmaceuticals, Inc. for advanced development of their influenza antiviral drug, peramivir.[4]
[edit] Spanish flu research
One theory is that the virus strain originated at Fort Riley, Kansas, by two genetic mechanisms — genetic drift and antigenic shift — in viruses in poultry and swine which the fort bred for local consumption. But evidence from a recent reconstruction of the virus suggests that it jumped directly from birds to humans, without traveling through swine.[25]
In February 1998, a team led by Jeffery Taubenberger of the US Armed Forces Institute of Pathology (AFIP) recovered samples of the 1918 influenza from the frozen corpse of a Native Alaskan woman buried for nearly eight decades in permafrost near Brevig Mission, Alaska. Brevig Mission lost approximately 85% of its population to the Spanish flu in November 1918. One of the four recovered samples contained viable genetic material of the virus. This sample provided scientists a first-hand opportunity to study the virus, which was inactivated with guanidinium thiocyanate before transport. This sample and others found in AFIP archives allowed researchers to completely analyze the critical gene structures of the 1918 virus. "We have now identified three cases: the Brevig Mission case and two archival cases that represent the only known sources of genetic material of the 1918 influenza virus", said Taubenberger, chief of AFIP's molecular pathology division and principal investigator on the project.[26][27]
Negative stained transmission electron micrograph (TEM) of recreated 1918 influenza virus.Wikinews has related news:
Scientists recreating the 1918 flu virus suggest that it may have come from birdsThe February 6, 2004 edition of Science magazine reported that two research teams, one led by Sir John Skehel, director of the National Institute for Medical Research in London, another by Professor Ian Wilson of The Scripps Research Institute in San Diego, had managed to synthesize the hemagglutinin protein responsible for the 1918 outbreak of Spanish Flu. They did this by piecing together DNA from a lung sample from an Inuit woman buried in the Alaskan tundra and a number of preserved samples from American soldiers of the First World War. The teams had analyzed the structure of the gene and discovered how subtle alterations to the shape of a protein molecule had allowed it to move from birds to humans with such devastating effects.
On October 5, 2005, researchers announced that the genetic sequence of the 1918 flu strain, a subtype of avian strain H1N1, had been reconstructed using historic tissue samples. [28]
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The H5N1 virus has mutated into a variety of types with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species. [29] The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types. [30] This doesn't mean one amino acid substitution can cause a pandemic but it does mean one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans.
In July 2004, researchers led by H. Deng of the Harbin Veterinary Research Institute, Harbin, China and Robert Webster of the St Jude Children's Research Hospital, Memphis, Tennessee, reported results of experiments in which mice had been exposed to 21 isolates of confirmed H5N1 strains obtained from ducks in China between 1999 and 2002. They found "a clear temporal pattern of progressively increasing pathogenicity". [31] Results reported by Webster in July 2005 reveal further progression toward pathogenicity in mice and longer virus shedding by ducks.
Recent research of Taubenberger et al has suggested that the 1918 virus, like H5N1, could have arisen directly from an avian influenza virus. [32] However, researchers at University of Virginia and Australian National University have suggested that there may be an alternative interpretation of the data used in the Taubenberger et al. paper.[33][34] Taubenberger et al responded to these letters and defended their original interpretation. [35]
Other research by Tumpey and colleagues who reconstructed the H1N1 virus of 1918 came to the conclusion that it is was most notably the polymerase genes and the HA and NA genes that caused the extreme virulence of this virus. [36] The sequences of the polymerase proteins (PA, PB1, and PB2) of the 1918 virus and subsequent human viruses differ by only 10 amino acids from the avian influenza viruses. Viruses with seven of the ten amino acids in the human influenza locations have already been identified in currently circulating H5N1. This has led some researchers to suggest that other mutations may surface and make the H5N1 virus capable of human-to-human transmission. Another important factor is the change of the HA protein to a binding preference for alpha 2,6 sialic acid (the major form in the human respiratory tract). In avian virus the HA protein preferentially binds to alpha 2,3 sialic acid, which is the major form in the avian enteric tract. It has been shown that only a single amino acid change can result in the change of this binding preference. Altogether, only a handful of mutations may need to take place in order for H5N1 avian flu to become a pandemic virus like the one of 1918. However it is important to note that likelihood of mutation does not indicate the likelihood for the evolution of such a strain; since some of the necessary mutations may be constrained by stabilizing selection.
On 18 January 2007, Kobasa et al reported that infected monkeys (Macaca fascicularis) exhibited classic symptoms of the 1918 pandemic and died from a cytokine storm.[37]
[edit] Blood plasma as an effective treatment
In the event of another pandemic, US military researchers have proposed reusing a treatment from the deadly pandemic of 1918 in order to blunt the effects of the flu. Some military doctors injected severely afflicted patients with blood or blood plasma from people who had recovered from the flu. Data collected during that time indicates that the blood-injection treatment reduced mortality rates by as much as 50 percent. Navy researchers have launched a test to see if the 1918 treatment will work against deadly Asian bird flu. Results thus far have been inconclusive. Human H5N1 plasma may be an effective, timely, and widely available treatment for the next flu pandemic. A new international study using modern data collection methods, would be a difficult, slow process. But many flu experts, citing the months-long wait for a vaccine for the next pandemic, are of the opinion that the 1918 method is something to consider.[38]
In the world wide Spanish flu pandemic of 1918, "physicians tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen, to developing new vaccines and sera (chiefly against what we now call Hemophilus influenzae—a name derived from the fact that it was originally considered the etiological agent—and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success."[39]
[edit] Sources and notes
^ Science and Development Network article Pandemic flu: fighting an enemy that is yet to exist published May 3, 2006.
^ Yahoo News AP article Bird Flu Vaccine Funding Awarded published May 4, 2006 (link expired).
^ New York Times article ""Doubt Cast on Stockpile of a Vaccine for Bird Flu""
^ ABC News
^ a b The NIH Biomedical Research Response to Influenza
^ CDC
^ WHO
^ phacilitate.co.uk
^ Canada TV News
^ MedImmune Press release MedImmune and National Institutes of Health Begin Clinical Testing of a Live, Attenuated Intranasal Vaccine Against an H5N1 Avian Influenza Virus published June 15, 2007
^ AVI BioPharma Reports Successful Inhibition of Multiple Subtypes of Influenza A Using NEUGENE Antisense Therapeutic
^ Ge, Q; Pastey, M, Kobasa, D, Puthavathana, P, Lupfer, C, Bestwick, RK, Iversen, PL, Chen, J, Stein, DA (2006). "Inhibition of Multiple Subtypes of Influenza A Virus in Cell Cultures with Morpholino Oligomers." (Pubmed). Antimicrob Agents Chemother. 50 (11): 3724-33.
^ ABC News article Scientists mull faster vaccine production published on April 12, 2006
^ [1]Bypassing eggs, flu vaccine grown in insect cells shows promise
^ CIDRAP article Panel supports EU approval of cell-based flu vaccine published April 27, 2007
^ US HHS (United States Department of Health & Human Services) Pandemic Influenza Plan Appendix F: Current HHS Activities last revised on November 8, 2005
^ Wired News JVI
^ Department of Health & Human Services
^ NPR
^ New England Journal of MedicineVolume 354:1411-1413 - March 30, 2006 - Number 13 - Vaccines against Avian Influenza — A Race against Time
^ Scientific American article U.S. approves first bird flu vaccine for people published April 17, 2007
^ The New York Times article First Vaccine Against Avian Flu Is Approved as Interim Measure published April 18, 2007
^ CIDRAP article FDA approves first H5N1 vaccine published April 17, 2007
^ Nature
^ Sometimes a virus contains both avian adapted genes and human adapted genes. Both the H2N2 and H3N2 pandemic strains contained avian flu virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source (Belshe 2005)." (from Chapter Two : Avian Influenza by Timm C. Harder and Ortrud Werner, an excellent free on-line Book called Influenza Report 2006 which is a medical textbook that provides a comprehensive overview of epidemic and pandemic influenza.)
^ Lethal secrets of 1918 flu virus; BBC
^ According to Gina Kolata's 1999 account of the pandemic, 'Flu', pp. 255-65 : Johan Hultin first attempted to recover samples from Brevig in 1951, but he was unsuccessful. In 1997, by then a seventy-two year old retired pathologist, he decided that science had advanced enough to make another attempt worthwhile. Taubenberger had already recovered RNA of limited quality from samples of two servicemen who had died in the pandemic, and Hultin wrote offering offering his services to try to get better quality samples from Brevig permafrost. Taubenberger accepted, and Hultin went alone to Brevig in August 1997, and recovered the sample from the Alaskan woman, which Taubenberger and his team then analysed.
^ Special report at Nature News: The 1918 flu virus is resurrected, Published online: 5 October 2005; doi:10.1038/437794a. See: Taubenberger, Jeffery K.; Ann H. Reid, Raina M. Lourens, Ruixue Wang, Guozhong Jin and Thomas G. Fanning (2005). "Characterization of the 1918 influenza virus polymerase genes". Nature 437: 889-893. DOI:10.1038/nature04230. . Also: Tumpey, Terrence M.; Christopher F. Basler, Patricia V. Aguilar, Hui Zeng, Alicia Solórzano, David E. Swayne, Nancy J. Cox, Jacqueline M. Katz, Jeffery K. Taubenberger, Peter Palese and Adolfo García-Sastre (2005). "Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus". Science 310: 77-80. DOI:10.1126/science.1119392.
^ Kou, Z.; F. M. Lei, J. Yu, Z. J. Fan, Z. H. Yin, C. X. Jia, K. J. Xiong, Y. H. Sun, X. W. Zhang, X. M. Wu, X. B. Gao and T. X. Li (2005). "New genotype of avian influenza H5N1 viruses isolated from tree sparrows in China". Journal of Virology 79: 15460-15466. PMID 16306617.
^ Evolution of the receptor binding phenotype of influenza A (H5) viruses by A. Gambaryan, A. Tuzikov, G. Pazynina, N. Bovin, A. Balish and A. Klimov in Virology (2005) electronic release on October 11 ahead of print publication.
^ The evolution of H5N1 influenza viruses in ducks in southern China by H. Chen, G. Deng, Z. Li, G. Tian, Y. Li, P. Jiao, L. Zhang, Z. Liu, R. G. Webster and K. Yu in Proceedings of the National Academy of Sciences of the United States of America (2004) volume 101, pages 10452-10457.
^ Recent research of Taubenberger et al has suggested that the 1918 virus, like H5N1, could have arisen directly from an avian influenza virus in:
Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature. October 6, 2005;437(7060):889-893
^ Was the 1918 pandemic caused by a bird flu? - Gibbs and Gibbs Nature. April 27, 2006;440:E8
^ Was the 1918 flu avian in origin? - Antonovics et al. Nature. April 27, 2006;440:E9
^ Molecular virology: Was the 1918 pandemic caused by a bird flu? Was the 1918 flu avian in origin? (Reply)
^ Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, Garcia-Sastre A. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science. October 7, 2005;310(5745):77-80
^ Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus Nature. 18 January 2007;445:319
^ npr.org history.navy.mil
^ The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) (free online book) page 62
[edit] See also
Global Alliance for Vaccines and Immunization
IFPMA International Federation of Pharmaceutical Manufacturers Associations
Reporting disease cases
Original antigenic sin
Center for Biologics Evaluation and Research
ICEID
Influenza Genome Sequencing Project
Cytokine storm
International Partnership on Avian and Pandemic Influenza
National Influenza Centers
Pandemic Preparedness and Response Act
[edit] References
^ Science and Development Network article Pandemic flu: fighting an enemy that is yet to exist published May 3, 2006.
^ Yahoo News AP article Bird Flu Vaccine Funding Awarded published May 4, 2006 (link expired).
^ New York Times article ""Doubt Cast on Stockpile of a Vaccine for Bird Flu""
^ ABC News
^ a b The NIH Biomedical Research Response to Influenza
^ CDC
^ WHO
^ phacilitate.co.uk
^ Canada TV News
^ MedImmune Press release MedImmune and National Institutes of Health Begin Clinical Testing of a Live, Attenuated Intranasal Vaccine Against an H5N1 Avian Influenza Virus published June 15, 2007
^ AVI BioPharma Reports Successful Inhibition of Multiple Subtypes of Influenza A Using NEUGENE Antisense Therapeutic
^ Ge, Q; Pastey, M, Kobasa, D, Puthavathana, P, Lupfer, C, Bestwick, RK, Iversen, PL, Chen, J, Stein, DA (2006). "Inhibition of Multiple Subtypes of Influenza A Virus in Cell Cultures with Morpholino Oligomers." (Pubmed). Antimicrob Agents Chemother. 50 (11): 3724-33.
^ ABC News article Scientists mull faster vaccine production published on April 12, 2006
^ [2]Bypassing eggs, flu vaccine grown in insect cells shows promise
^ CIDRAP article Panel supports EU approval of cell-based flu vaccine published April 27, 2007
^ US HHS (United States Department of Health & Human Services) Pandemic Influenza Plan Appendix F: Current HHS Activities last revised on November 8, 2005
^ Wired News JVI
^ Department of Health & Human Services
^ NPR
^ New England Journal of MedicineVolume 354:1411-1413 - March 30, 2006 - Number 13 - Vaccines against Avian Influenza — A Race against Time
^ Scientific American article U.S. approves first bird flu vaccine for people published April 17, 2007
^ The New York Times article First Vaccine Against Avian Flu Is Approved as Interim Measure published April 18, 2007
^ CIDRAP article FDA approves first H5N1 vaccine published April 17, 2007
^ Nature
^ Sometimes a virus contains both avian adapted genes and human adapted genes. Both the H2N2 and H3N2 pandemic strains contained avian flu virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source (Belshe 2005)." (from Chapter Two : Avian Influenza by Timm C. Harder and Ortrud Werner, an excellent free on-line Book called Influenza Report 2006 which is a medical textbook that provides a comprehensive overview of epidemic and pandemic influenza.)
^ Lethal secrets of 1918 flu virus; BBC
^ According to Gina Kolata's 1999 account of the pandemic, 'Flu', pp. 255-65 : Johan Hultin first attempted to recover samples from Brevig in 1951, but he was unsuccessful. In 1997, by then a seventy-two year old retired pathologist, he decided that science had advanced enough to make another attempt worthwhile. Taubenberger had already recovered RNA of limited quality from samples of two servicemen who had died in the pandemic, and Hultin wrote offering offering his services to try to get better quality samples from Brevig permafrost. Taubenberger accepted, and Hultin went alone to Brevig in August 1997, and recovered the sample from the Alaskan woman, which Taubenberger and his team then analysed.
^ Special report at Nature News: The 1918 flu virus is resurrected, Published online: 5 October 2005; doi:10.1038/437794a. See: Taubenberger, Jeffery K.; Ann H. Reid, Raina M. Lourens, Ruixue Wang, Guozhong Jin and Thomas G. Fanning (2005). "Characterization of the 1918 influenza virus polymerase genes". Nature 437: 889-893. DOI:10.1038/nature04230. . Also: Tumpey, Terrence M.; Christopher F. Basler, Patricia V. Aguilar, Hui Zeng, Alicia Solórzano, David E. Swayne, Nancy J. Cox, Jacqueline M. Katz, Jeffery K. Taubenberger, Peter Palese and Adolfo García-Sastre (2005). "Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus". Science 310: 77-80. DOI:10.1126/science.1119392.
^ Kou, Z.; F. M. Lei, J. Yu, Z. J. Fan, Z. H. Yin, C. X. Jia, K. J. Xiong, Y. H. Sun, X. W. Zhang, X. M. Wu, X. B. Gao and T. X. Li (2005). "New genotype of avian influenza H5N1 viruses isolated from tree sparrows in China". Journal of Virology 79: 15460-15466. PMID 16306617.
^ Evolution of the receptor binding phenotype of influenza A (H5) viruses by A. Gambaryan, A. Tuzikov, G. Pazynina, N. Bovin, A. Balish and A. Klimov in Virology (2005) electronic release on October 11 ahead of print publication.
^ The evolution of H5N1 influenza viruses in ducks in southern China by H. Chen, G. Deng, Z. Li, G. Tian, Y. Li, P. Jiao, L. Zhang, Z. Liu, R. G. Webster and K. Yu in Proceedings of the National Academy of Sciences of the United States of America (2004) volume 101, pages 10452-10457.
^ Recent research of Taubenberger et al has suggested that the 1918 virus, like H5N1, could have arisen directly from an avian influenza virus in:
Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature. October 6, 2005;437(7060):889-893
^ Was the 1918 pandemic caused by a bird flu? - Gibbs and Gibbs Nature. April 27, 2006;440:E8
^ Was the 1918 flu avian in origin? - Antonovics et al. Nature. April 27, 2006;440:E9
^ Molecular virology: Was the 1918 pandemic caused by a bird flu? Was the 1918 flu avian in origin? (Reply)
^ Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, Garcia-Sastre A. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science. October 7, 2005;310(5745):77-80
^ Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus Nature. 18 January 2007;445:319
^ npr.org history.navy.mil
^ The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) (free online book) page 62
[edit] Further reading
WHO's assessment of FLU RESEARCH as of November 2006
[hide]v • d • eInfluenza
Influenza Research - Vaccine - Avian influenza - Treatment - Genome sequencing
Influenza viruses Orthomyxoviridae - Influenzavirus A - Influenzavirus B - Influenzavirus C
Subtypes of type A flu H1N1 - H1N2 - H2N2 - H3N2 - H3N8 - H5N1 - H5N2 - H5N3 - H5N8 - H5N9 - H7N1 - H7N2 - H7N3 - H7N4 - H7N7 - H9N2 - H10N7
H5N1 Genetic structure - Transmission and infection - Global spread - Clinical Trials - Human mortality
Antiviral drugs Arbidol - adamantane derivatives (Amantadine, Rimantadine)- neuraminidase inhibitors (Oseltamivir, Peramivir, Zanamivir)
Experimental (Peramivir)
Flu vaccines FluMist - Fluzone
Influenza pandemics Asian Flu - Hong Kong Flu - Spanish Flu - Fujian flu - Pandemic Severity Index
Influenza in non-human mammals Dog flu - Horse flu - Swine flu
Retrieved from "http://en.wikipedia.org/wiki/Flu_research"
Categories: Influenza | Research
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