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Encyclopedia > Influenza research
Flu

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. Image File history File links Flu_und_legende_color_c. ... Influenza, commonly known as flu, is an infectious disease of birds and mammals caused by an RNA virus of the family Orthomyxoviridae (the influenza viruses). ... Genera Influenzavirus A Influenzavirus B Influenzavirus C Isavirus Thogotovirus The Orthomyxoviridae are a family of RNA viruses which infect vertebrates. ... Avian influenza (also known as bird flu, avian flu, influenzavirus A flu, type A flu, or genus A flu) is a flu (influenza) due to a type of influenza virus that is hosted by birds, but may infect several species of mammals. ... Flu season is mostly a colloquial term used to describe the regular outbreak in flu cases, or even cases of the common cold during the late fall or winter. ... Model of Influenza Virus from NIH The flu vaccine is a vaccine to protect against the highly variable influenza virus. ... This article is about flu treatment in humans for mild human flu, which includes both efforts to reduce symptoms and to battle the flu virus itself. ... The Influenza Genome Sequencing Project is funded by the National Institute of Allergy and Infectious Diseases (NIAID) which is a component of the National Institutes of Health (NIH), which is an agency of the United States Department of Health and Human Services. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... Molecular Virology is the study of viruses at the molecular level. ... Pathogenesis is the mechanism by which a certain etiological factor causes disease (pathos = disease, genesis = development). ... A request has been made on Wikipedia for this article to be deleted in accordance with the deletion policy. ... Genomics is the study of an organisms entire genome; Rathore et al, . Investigation of single genes, their functions and roles is something very common in todays medical and biological research, and cannot be said to be genomics but rather the most typical feature of molecular biology. ... Epidemiology is the study of factors affecting the health and illness of populations, and serves as the foundation and logic of interventions made in the interest of public health and preventive medicine. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ...


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] Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... Model of Influenza Virus from NIH The flu vaccine is a vaccine to protect against the highly variable influenza virus. ...


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. The Influenza Genome Sequencing Project is funded by the National Institute of Allergy and Infectious Diseases (NIAID) which is a component of the National Institutes of Health (NIH), which is an agency of the United States Department of Health and Human Services. ... This page is a candidate to be copied to Wiktionary using the Transwiki process. ...

Contents

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: is the 124th day of the year (125th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... This article or section does not adequately cite its references or sources. ... In most birds and reptiles, an egg (Latin ovum) is the zygote, resulting from fertilization of the ovum. ...

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] GlaxoSmithKline plc (LSE: GSK NYSE: GSK) is a British based pharmaceutical, biological, and healthcare company. ... This article deals with the company named Solvay. ... ... Sanofi pasteur is the vaccines business of sanofi-aventis Group. ... Chiron Corporation (NASDAQ: NVS) was a multinational biotechnology firm based in Emeryville, California that was acquired by Novartis International AG on April 30, 2006. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ... An influenza pandemic is a large scale epidemic of the influenza virus, such as the 1918 Spanish flu. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... is the 91st day of the year (92nd in leap years) in the Gregorian calendar. ...


"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] H9N2 is a subtype of the species avian influenza virus (bird flu virus). ... National Institute of Allergy and Infectious Diseases (NIAID) is a component of the National Institutes of Health (NIH), which is an agency of the United States Department of Health and Human Services. ... Chiron Corporation (NASDAQ: NVS) was a multinational biotechnology firm based in Emeryville, California that was acquired by Novartis International AG on April 30, 2006. ... National Institute of Allergy and Infectious Diseases (NIAID) is a component of the National Institutes of Health (NIH), which is an agency of the United States Department of Health and Human Services. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... The United States Department of Health and Human Services, often abbreviated HHS, is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential human services. ...


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] A vaccine is an antigenic preparation used to establish immunity to a disease. ...


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. In medicine, adjuvants are agents which modify the effect of other agents while having few if any direct effects when given by themselves. ... A crystal of alum Alum, (IPA: ) (aluminium potassium sulfate,) in chemistry, is a term given to the crystallized double sulfates of the typical formula M+2SO4·M3+2(SO4)3·24H2O, where M+ is the sign of an alkali metal (lithium, sodium, potassium, rubidium, or caesium), and M3+ denotes one... A clade is a term belonging to the discipline of cladistics. ...


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] National Institutes of Health Building 50 at NIH Clinical Center - Building 10 The National Institutes of Health (NIH) is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical research. ... H5N1 clinical trials are clinical trials concerning H5N1 vaccine; which is to say they are investigations concerning H5N1 vaccine in humans intended to discover pharmacological effects and identify any adverse reactions. ... Model of Influenza Virus from NIH The flu vaccine is a vaccine to protect against the highly variable influenza virus. ... MedImmune is a Maryland-based biotechnology company. ... FluMist is the product name of a nasal spray vaccine against the flu virus. ...


Reverse genetics

A 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. Image File history File linksMetadata Download high-resolution version (2145x2620, 1177 KB) This image is a work of the National Institutes of Health, part of the United States Department of Health and Human Services. ... Image File history File linksMetadata Download high-resolution version (2145x2620, 1177 KB) This image is a work of the National Institutes of Health, part of the United States Department of Health and Human Services. ... For the current concern about the transmission of an avian flu to humans see Transmission and infection of H5N1. ... Reverse genetics is an approach to discovering the function of a gene that proceeds in the opposite direction of so called forward genetic screens that are more usual in classical genetics. ... National Institute of Allergy and Infectious Diseases (NIAID) is a component of the National Institutes of Health (NIH), which is an agency of the United States Department of Health and Human Services. ... Reverse genetics is an approach to discovering the function of a gene that proceeds in the opposite direction of so called forward genetic screens that are more usual in classical genetics. ... In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... For a non-technical introduction to the topic, see Introduction to Genetics. ...


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] Epithelial cells in culture, stained for keratin (red) and DNA (green) Cell culture is the process by which either prokaryotic or eukaryotic cells are grown under controlled conditions. ... The baculoviruses are a family of large rod-shaped viruses that can be divided to two genera: nucleopolyhedroviruses (NPV) and granuloviruses (GV). ... Hemagglutinin, as depicted in a simplified molecular model. ... Neuraminidase is a glycoside hydrolase enzyme (EC 3. ...


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] Influenza A virus, the virus that causes Avian flu. ... Epithelial cells in culture, stained for keratin (red) and DNA (green) Cell culture is the process by which either prokaryotic or eukaryotic cells are grown under controlled conditions. ... Segment of a Morpholino-RNA heteroduplex, 8-mer shown In molecular biology, a Morpholino is a kind of molecule used to modify gene expression. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ...


"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] For the server security software, see Microsoft Forefront. ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... The structure of insulin Biological technology is technology based on biology, especially when used in agriculture, food science, and medicine. ... Binomial name Escherichia coli T. Escherich, 1885 Escherichia coli (usually abbreviated to E. coli) is one of the main species of bacteria that live in the lower intestines of warm-blooded animals (including birds and mammals) and are necessary for the proper digestion of food. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ... Hemagglutinin, as depicted in a simplified molecular model. ...


"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]


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]: The United States Department of Health and Human Services, often abbreviated HHS, is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential human services. ...

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.

A vaccine is an antigenic preparation used to establish immunity to a disease. ... Hemagglutinin, as depicted in a simplified molecular model. ... Neuraminidase is a glycoside hydrolase enzyme (EC 3. ... For the server security software, see Microsoft Forefront. ... In most birds and reptiles, an egg (Latin ovum) is the zygote, resulting from fertilization of the ovum. ... Avian influenza (also known as bird flu, avian flu, influenzavirus A flu, type A flu, or genus A flu) is a flu (influenza) due to a type of influenza virus that is hosted by birds, but may infect several species of mammals. ... This article or section does not adequately cite its references or sources. ... Epithelial cells in culture, stained for keratin (red) and DNA (green) Cell culture is the process by which either prokaryotic or eukaryotic cells are grown under controlled conditions. ... By the mid 20th century humans had achieved a mastery of technology sufficient to leave the surface of the Earth for the first time and explore space. ... Poliomyelitis (polio), or infantile paralysis, is a viral paralytic disease. ... Rubella, commonly known as German measles, is a disease caused by the rubella virus. ... South Park episode, see Chickenpox (South Park episode). ... A bioreactor may refer to any device or system that supports a biologically active environment. ... A request has been made on Wikipedia for this article to be deleted in accordance with the deletion policy. ... Hemagglutinin, as depicted in a simplified molecular model. ... For the server security software, see Microsoft Forefront. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... For the current concern about the transmission of an avian flu to humans see Transmission and infection of H5N1. ... Manufacturing is the transformation of raw materials into finished goods for sale, or intermediate processes involving the production or finishing of semi-manufactures. ... In medicine, adjuvants are agents which modify the effect of other agents while having few if any direct effects when given by themselves. ... // COUNCIL DIRECTIVE 93/42/EEC of 14 June 1993 concerning medical devices defines a ‘medical device’ as: any instrument, apparatus, appliance, material or other article, whether used alone or in combination, including the software necessary for its proper application intended by the manufacturer to be used for human beings for...

H5N1 vaccine research

See also: H5N1 clinical trials
H5N1
WHO pandemic phases
  1. Low risk
  2. New virus
  3. Self limiting
  4. Person to person
  5. Epidemic exists
  6. Pandemic exists
Model of H5N1 virus
Model of H5N1 virus

There 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. H5N1 clinical trials are clinical trials concerning H5N1 vaccine; which is to say they are investigations concerning H5N1 vaccine in humans intended to discover pharmacological effects and identify any adverse reactions. ... Image File history File links Colorized_transmission_electron_micrograph_of_Avian_influenza_A_H5N1_viruses. ... Genera Influenzavirus A Influenzavirus B Influenzavirus C Isavirus Thogotovirus Influenzavirus A is a genus of the family of viruses called Orthomyxoviridae in virus classification. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... H5N1 genetic structure refers to the molecular structure of the H5N1 viruss RNA. H5N1 is an Influenza A virus subtype. ... See Epidemiology of WHO-confirmed human cases of avian influenza A(H5N1) infection. ... The thin line represents average mortality of recent cases. ... The global spread of H5N1 in birds is considered a significant pandemic threat. ... Main article: Global spread of H5N1 Notes: Source WHO Confirmed Human Cases of H5N1 [T]he incidence of human cases peaked, in each of the three years in which cases have occurred, during the period roughly corresponding to winter and spring in the northern hemisphere. ... See Influenza pandemic for government preparation for an H5N1 pandemic H5N1 impact is the effect or influence of H5N1 in human society; especially the financial, political, social and personal responses to both actual and predicted deaths in birds, humans, and other animals. ... An influenza pandemic is a large scale epidemic of the influenza virus, such as the 1918 Spanish flu. ... An influenza pandemic is a large scale epidemic of the influenza virus, such as the 1918 Spanish flu. ... Image File history File links Flu_und_legende_color_c. ... Image File history File links Flu_und_legende_color_c. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... This article is about large epidemics. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ...


Problems with H5N1 vaccine production include: Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ...

  • 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] Epithelial cells in culture, stained for keratin (red) and DNA (green) Cell culture is the process by which either prokaryotic or eukaryotic cells are grown under controlled conditions. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ...


According to the United States Department of Health & Human Services: The United States Department of Health and Human Services, often abbreviated HHS, is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential 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] A vaccine is an antigenic preparation used to establish immunity to a disease. ... Hemagglutinin, as depicted in a simplified molecular model. ... For the server security software, see Microsoft Forefront. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... In medicine, adjuvants are agents which modify the effect of other agents while having few if any direct effects when given by themselves. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ... In medicine, adjuvants are agents which modify the effect of other agents while having few if any direct effects when given by themselves. ... Chiron Corporation (NASDAQ: NVS) was a multinational biotechnology firm based in Emeryville, California that was acquired by Novartis International AG on April 30, 2006. ... National Institutes of Health Building 50 at NIH Clinical Center - Building 10 The National Institutes of Health (NIH) is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical research. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ...


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] The New England Journal of Medicine (New Engl J Med or NEJM) is a peer-reviewed medical journal published by the Massachusetts Medical Society. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ...


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] Model of Influenza Virus from NIH The flu vaccine is a vaccine to protect against the highly variable influenza virus. ... Sanofi-aventis (Euronext: SAN, NYSE: SNY), headquartered in Paris, France, is one of the 3 largest pharmaceutical companies in the world, along with Pfizer,GlaxoSmithKline. ... Swiftwater is a city in Monroe County, Pennsylvania. ...


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]


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. Antiviral drugs are a class of medication used specifically for treating viral infections. ... Oseltamivir (INN) (IPA: ) is an antiviral drug that is used in the treatment and prophylaxis of both Influenzavirus A and Influenzavirus B. Like zanamivir, oseltamivir is a neuraminidase inhibitor. ... Zanamivir is a neuraminidase inhibitor used in the treatment of and prophylaxis of both influenza A and influenza B. Zanamivir was the first neuraminidase inhibitor commercially developed. ...


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] Probenecid is a uricosuric drug, primarily used in treating gout or hyperuricemia, that increases uric acid removal in the urine. ...


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] Peramivir is a pharmaceutical drug used to viral infections. ... Zanamivir is a neuraminidase inhibitor used in the treatment of and prophylaxis of both influenza A and influenza B. Zanamivir was the first neuraminidase inhibitor commercially developed. ... Oseltamivir (INN) (IPA: ) is an antiviral drug that is used in the treatment and prophylaxis of both Influenzavirus A and Influenzavirus B. Like zanamivir, oseltamivir is a neuraminidase inhibitor. ... Neuraminidase inhibitors are a class of antiviral drugs, whose mode of action relies on blocking the function of viral neuraminidase protein, thus preventing the virus from budding from the host cell. ... The transition state of a chemical reaction is a particular configuration along the reaction coordinate. ... Neuraminidase is a glycoside hydrolase enzyme (EC 3. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ... Hepatitis B is an inflammation of the liver and is caused by the Hepatitis B virus (HBV), a member of the Hepadnavirus family[1] and one of hundreds of unrelated viral species which cause viral hepatitis. ... Poliomyelitis (polio), or infantile paralysis, is a viral paralytic disease. ... Smallpox (also known by the Latin names Variola or Variola vera) is a contagious disease unique to humans. ...


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] Fort Riley is a census-designated place and United States Army post, in Northeast Kansas, on the Kansas River. ... Official language(s) English[2] Capital Topeka Largest city Wichita Area  Ranked 15th  - Total 82,277 sq mi (213,096 km²)  - Width 211 miles (340 km)  - Length 417 miles (645 km)  - % water 0. ... This article is about the general scientific term. ... In population genetics, genetic drift is the statistical effect that results from the influence that chance has on the success of alleles (variants of a gene). ... Antigenic shift is the process by which two different strains of influenza combine to form a new subtype having a mixture of the surface antigens of the two original strains. ... Avian influenza (also known as bird flu) is a type of influenza virulent in birds. ...


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] Year 1998 (MCMXCVIII) was a common year starting on Thursday (link will display full 1998 Gregorian calendar). ... To meet Wikipedias quality standards, this article or section may require cleanup. ... In geology, permafrost or permafrost soil is soil at or below the freezing point of water (0°C or 32°F) for two or more years. ... Brevig Mission is a city located in Nome Census Area, Alaska. ... Guanidinium thiocyanate is a chemical compound that can be used to deactivate a virus, such as the influenza virus that caused the 1918 Spanish flu so that it can be studied safely. ... For a non-technical introduction to the topic, see Introduction to Genetics. ... Genetic material is used to store the genetic information of an organic life form. ...

Negative stained transmission electron micrograph (TEM) of recreated 1918 influenza virus.
Negative stained transmission electron micrograph (TEM) of recreated 1918 influenza virus.

The 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. Image File history File links Reconstructed_Spanish_Flu_Virus. ... Image File history File links Reconstructed_Spanish_Flu_Virus. ... A section of a cell of Bacillus subtilis, taken with a Tecnai T-12 TEM. The scale bar is 200nm. ... This article is about biological infectious particles. ... Image File history File links WikiNews-Logo. ... Wikinews is a free-content news source and a project of the Wikimedia Foundation. ... is the 37th day of the year in the Gregorian calendar. ... Year 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ... Science is the journal of the American Association for the Advancement of Science (AAAS). ... The National Institute For Medical Research, commonly abbreviated to NIMR, is a large medical research facility situated in rural Mill Hill, England, on the outskirts of London. ... This article is about the capital of England and the United Kingdom. ... Ian Wilson is a professor at the Scripps Research Institute in San Diego, California, United States. ... TSRIs Beckman Center for Chemical Sciences The Scripps Research Institute (TSRI) is a medical research facility that focuses on research in the basic biomedical sciences. ... Flag Seal Nickname: Americas Finest City Location Location of San Diego within San Diego County Coordinates , Government County San Diego Mayor City Attorney         City Council District One District Two District Three District Four District Five District Six District Seven District Eight Jerry Sanders (R) Michael Aguirre Scott Peters Kevin... Hemagglutinin, as depicted in a simplified molecular model. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... For other uses, see Inuit (disambiguation). ... For other uses, see Tundra (disambiguation). ...


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] is the 278th day of the year (279th in leap years) in the Gregorian calendar. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ...


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. Influenza, commonly known as flu, is an infectious disease of birds and mammals caused by an RNA virus of the family Orthomyxoviridae (the influenza viruses). ... An RNA virus is a virus that either uses RNA as its genetic material, or whose genetic material passes through an RNA intermediate during replication. ... It has been suggested that mutant be merged into this article or section. ... Phenylalanine is one of the standard amino acids. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ...


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. 2004 : January - February - March - April - May - June - July - August - September - October - November - December See also: July 2004 in sports Deaths in July • 31 David B. Haight • 29 Francis Crick • 29 Nafisa Joseph • 23 Joe Cahill • 23 Mehmood • 23 Illinois Jacquet • 23 Carlos Paredes... Harbin on a map of China For other meanings of Harbin, see Harbin (disambiguation). ... Robert G. (Rob) Webster (born May 7, 1932), in Balclutha New Zealand, is the virologist who in 1957 was the first to announce a link between human flu and bird flu. ... From the stjude. ... For other uses, see Memphis (disambiguation). ... Feral mouse A mouse (plural mice) is a rodent that belongs to one of numerous species of small mammals. ... Ongoing events • 2005 Atlantic and Pacific hurricanes • 2005 Maharashtra floods • 2005 Gujarat Flood • Expo 2005 in Aichi, Japan • Fuel prices • Gomery Comm. ...


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. Stabilizing selection, also known as purifying selection or negative selection, is a type of natural selection in which genetic diversity decreases as the population stabilizes on a particular trait value. ...


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] is the 18th day of the year in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... Binomial name Macaca fascicularis Raffles, 1821 The Crab-eating Macaque (Macaca fascicularis) is an arboreal macaque native to South-East Asia. ... A cytokine storm is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells. ...


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] Blood plasma is the liquid component of blood, in which the blood cells are suspended. ... Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. ...


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] The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1. ... Binomial name Haemophilus influenzae Lehmann & Neumann, 1896 Haemophilus influenzae, formerly called Pfeiffers bacillus, is a non-motile Gram-negative coccobacillus first described in 1892 by Dr. Robert Pfeiffer during the influenza pandemic. ...


Sources and notes

  1. ^ Science and Development Network article Pandemic flu: fighting an enemy that is yet to exist published May 3, 2006.
  2. ^ Yahoo News AP article Bird Flu Vaccine Funding Awarded published May 4, 2006 (link expired).
  3. ^ New York Times article ""Doubt Cast on Stockpile of a Vaccine for Bird Flu""
  4. ^ ABC News
  5. ^ a b The NIH Biomedical Research Response to Influenza
  6. ^ CDC
  7. ^ WHO
  8. ^ phacilitate.co.uk
  9. ^ Canada TV News
  10. ^ 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
  11. ^ AVI BioPharma Reports Successful Inhibition of Multiple Subtypes of Influenza A Using NEUGENE Antisense Therapeutic
  12. ^ 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. 
  13. ^ ABC News article Scientists mull faster vaccine production published on April 12, 2006
  14. ^ [1]Bypassing eggs, flu vaccine grown in insect cells shows promise
  15. ^ CIDRAP article Panel supports EU approval of cell-based flu vaccine published April 27, 2007
  16. ^ US HHS (United States Department of Health & Human Services) Pandemic Influenza Plan Appendix F: Current HHS Activities last revised on November 8, 2005
  17. ^ Wired News JVI
  18. ^ Department of Health & Human Services
  19. ^ NPR
  20. ^ New England Journal of MedicineVolume 354:1411-1413 - March 30, 2006 - Number 13 - Vaccines against Avian Influenza — A Race against Time
  21. ^ Scientific American article U.S. approves first bird flu vaccine for people published April 17, 2007
  22. ^ The New York Times article First Vaccine Against Avian Flu Is Approved as Interim Measure published April 18, 2007
  23. ^ CIDRAP article FDA approves first H5N1 vaccine published April 17, 2007
  24. ^ Nature
  25. ^ 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.)
  26. ^ Lethal secrets of 1918 flu virus; BBC
  27. ^ 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.
  28. ^ 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. 
  29. ^ 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. 
  30. ^ 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.
  31. ^ 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.
  32. ^ 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
  33. ^ Was the 1918 pandemic caused by a bird flu? - Gibbs and Gibbs Nature. April 27, 2006;440:E8
  34. ^ Was the 1918 flu avian in origin? - Antonovics et al. Nature. April 27, 2006;440:E9
  35. ^ Molecular virology: Was the 1918 pandemic caused by a bird flu? Was the 1918 flu avian in origin? (Reply)
  36. ^ 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
  37. ^ Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus Nature. 18 January 2007;445:319
  38. ^ npr.org history.navy.mil
  39. ^ The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) (free online book) page 62

Medline is a comprehensive literature database of life sciences and biomedical information. ... The United States Department of Health and Human Services, often abbreviated HHS, is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential human services. ... The Asian Flu was a pandemic outbreak of influenza that originated in China in 1957 and spread worldwide that same year. ... H3N2 is a subtype of the species Influenza A virus (sometimes called bird flu virus). ... Ribonucleic acid or RNA is a nucleic acid polymer consisting of nucleotide monomers that plays several important roles in the processes that translate genetic information from deoxyribonucleic acid (DNA) into protein products; RNA acts as a messenger between DNA and the protein synthesis complexes known as ribosomes, forms vital portions... The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1. ... The British Broadcasting Corporation, which is usually known as the BBC, is the largest broadcasting corporation in the world in terms of audience numbers, employing 26,000 staff in the United Kingdom alone and with a budget of more than GB£4 billion. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Science is the journal of the American Association for the Advancement of Science (AAAS). ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences. ... is the 279th day of the year (280th in leap years) in the Gregorian calendar. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... April 27 is the 117th day of the year (118th in leap years) in the Gregorian calendar, with 248 days remaining. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... April 27 is the 117th day of the year (118th in leap years) in the Gregorian calendar, with 248 days remaining. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... 1918 (MCMXVIII) was a common year starting on Tuesday of the Gregorian calendar (see link for calendar) or a common year starting on Wednesday of the Julian calendar. ... is the 280th day of the year (281st in leap years) in the Gregorian calendar. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... is the 18th day of the year in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ...

See also

The Global Alliance for Vaccines and Immunization is an alliance between various UN organizations, national governments, private foundations, NGOs and the pharmaceutical industry. ... The IFPMA is the International Federation of Pharmaceutical Manufacturers and Associations. ... Reporting disease cases refers to modern international human infectious disease surveillance. ... Original antigenic sin (first described in 1960 by Thomas Francis, Jr. ... The Center for Biologics Evaluation and Research (CBER) is one of five main centers for the United Statess Food and Drug Administration (US FDA). ... The ICEID or International Conference on Emerging Infectious Diseases was first convened in 1998; ICEID 2006 marks its fifth occurence. ... The Influenza Genome Sequencing Project is funded by the National Institute of Allergy and Infectious Diseases (NIAID) which is a component of the National Institutes of Health (NIH), which is an agency of the United States Department of Health and Human Services. ... A cytokine storm is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells. ... President George W. Bush announced the International Partnership on Avian and Pandemic Influenza in his remarks to the High-Level Plenary Meeting of the United Nations General Assembly on September 14, 2005, in New York. ... National Influenza Centers (also called National Influenza Centres) are institutions which are formally recognized as such by WHO. Among the more than 110 National Influenza Centers are the WHO collaborating centres and reference laboratories that are involved in annual influenza vaccine composition recommendations. ... The Pandemic Preparedness and Response Act is a bill introduced on October 5, 2005 by Democratic Senators Harry Reid, Evan Bayh, Dick Durbin, Ted Kennedy, Barack Obama, and Tom Harkin in response to the growing threat of an outbreak of the Avian Flu. ...

References

  1. ^ Science and Development Network article Pandemic flu: fighting an enemy that is yet to exist published May 3, 2006.
  2. ^ Yahoo News AP article Bird Flu Vaccine Funding Awarded published May 4, 2006 (link expired).
  3. ^ New York Times article ""Doubt Cast on Stockpile of a Vaccine for Bird Flu""
  4. ^ ABC News
  5. ^ a b The NIH Biomedical Research Response to Influenza
  6. ^ CDC
  7. ^ WHO
  8. ^ phacilitate.co.uk
  9. ^ Canada TV News
  10. ^ 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
  11. ^ AVI BioPharma Reports Successful Inhibition of Multiple Subtypes of Influenza A Using NEUGENE Antisense Therapeutic
  12. ^ 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. 
  13. ^ ABC News article Scientists mull faster vaccine production published on April 12, 2006
  14. ^ [2]Bypassing eggs, flu vaccine grown in insect cells shows promise
  15. ^ CIDRAP article Panel supports EU approval of cell-based flu vaccine published April 27, 2007
  16. ^ US HHS (United States Department of Health & Human Services) Pandemic Influenza Plan Appendix F: Current HHS Activities last revised on November 8, 2005
  17. ^ Wired News JVI
  18. ^ Department of Health & Human Services
  19. ^ NPR
  20. ^ New England Journal of MedicineVolume 354:1411-1413 - March 30, 2006 - Number 13 - Vaccines against Avian Influenza — A Race against Time
  21. ^ Scientific American article U.S. approves first bird flu vaccine for people published April 17, 2007
  22. ^ The New York Times article First Vaccine Against Avian Flu Is Approved as Interim Measure published April 18, 2007
  23. ^ CIDRAP article FDA approves first H5N1 vaccine published April 17, 2007
  24. ^ Nature
  25. ^ 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.)
  26. ^ Lethal secrets of 1918 flu virus; BBC
  27. ^ 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.
  28. ^ 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. 
  29. ^ 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. 
  30. ^ 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.
  31. ^ 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.
  32. ^ 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
  33. ^ Was the 1918 pandemic caused by a bird flu? - Gibbs and Gibbs Nature. April 27, 2006;440:E8
  34. ^ Was the 1918 flu avian in origin? - Antonovics et al. Nature. April 27, 2006;440:E9
  35. ^ Molecular virology: Was the 1918 pandemic caused by a bird flu? Was the 1918 flu avian in origin? (Reply)
  36. ^ 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
  37. ^ Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus Nature. 18 January 2007;445:319
  38. ^ npr.org history.navy.mil
  39. ^ The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) (free online book) page 62

Medline is a comprehensive literature database of life sciences and biomedical information. ... The United States Department of Health and Human Services, often abbreviated HHS, is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential human services. ... The Asian Flu was a pandemic outbreak of influenza that originated in China in 1957 and spread worldwide that same year. ... H3N2 is a subtype of the species Influenza A virus (sometimes called bird flu virus). ... Ribonucleic acid or RNA is a nucleic acid polymer consisting of nucleotide monomers that plays several important roles in the processes that translate genetic information from deoxyribonucleic acid (DNA) into protein products; RNA acts as a messenger between DNA and the protein synthesis complexes known as ribosomes, forms vital portions... The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1. ... The British Broadcasting Corporation, which is usually known as the BBC, is the largest broadcasting corporation in the world in terms of audience numbers, employing 26,000 staff in the United Kingdom alone and with a budget of more than GB£4 billion. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Science is the journal of the American Association for the Advancement of Science (AAAS). ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences. ... is the 279th day of the year (280th in leap years) in the Gregorian calendar. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... April 27 is the 117th day of the year (118th in leap years) in the Gregorian calendar, with 248 days remaining. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... April 27 is the 117th day of the year (118th in leap years) in the Gregorian calendar, with 248 days remaining. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... 1918 (MCMXVIII) was a common year starting on Tuesday of the Gregorian calendar (see link for calendar) or a common year starting on Wednesday of the Julian calendar. ... is the 280th day of the year (281st in leap years) in the Gregorian calendar. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... is the 18th day of the year in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ...

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