اخر الابحاث عن انفلونزا الطيور
Shape Of Sugar Molecule Could Be All That Is Stopping Bird Flu Pandemic
US scientists have found that the shape of sugar molecules on cell surfaces in the upper respiratory tract determine how easy it is for influenza viruses to infect humans, and suggest that if the deadly strain of H5N1 bird flu were to adapt a way to bind to this shape of sugar molecule it would spread easily from human to human and provoke a world pandemic.
The study, which is funded by the US National Institutes of Health (NIH) is published in the 6th of January early online issue of <em>Nature Biotechnology</em>. The research team that conducted the study was led by Dr Ram Sasisekharan, of the Massachusetts Institute of Technology in Cambridge.
The deadly strain of H5N1 can only pass from bird to human, because it does not have the ability to spread via coughing and sneezing since the virus does not yet have a way of gaining entry to cells in the human upper respiratory tract.
In this study Sasisekharan and colleagues have discovered what makes it possible for some flu viruses to gain a foothold in the cells lining our noses and throats and why other strains find it more difficult.
Dr Jeremy M. Berg, director of the National Institute of General Medical Sciences (the part of NIH that sponsored the research) said:
"Using an approach that combines experimentation and database analysis, Sasisekharan's team has changed our view of flu viruses and how they must adapt to infect us."
"The work may improve our ability to monitor the evolution of the H5N1 virus and thwart potential outbreaks," he added.
The researchers were interested in a group of sugars called glycans. These are long chain molecules of different shapes that sit on the surfaces of cells and control entry into them. They are like gatekeepers of the cells and only let in agents that have the correct protein (rather like a "pass key"). Some viruses can get in because they have the correct protein to bind with the appropriate glycan.
The flu virus has a pass key called hemagglutinin, a protein that is slightly different for each strain of flu, and latches onto glycans for different cell types. The hemagglutinin of flu viruses that transmit easily between humans are able to bind to the glycans of the cells in the upper respiratory tract (the ones that line the nose and throat).
But the bird flu virus does not have the right type of hemagglutinin to gain access to the upper respiratory tract, it can only bind with glycans on the surfaces of lower respiratory tract cells.
However, Sasisekharan had seen some studies that found bird flu hemagglutinin had sometimes been able to bind to glycans on cells in the upper respiratory tract, and was puzzled as to why the virus didn't spread very well. So he and his team decided to investigate this.
They consulted a database maintained by the Consortium for Functional Glycomics (CFG) which holds information on the interactions between proteins and different types of glycan sugars.
They used the CFG glycan preference array which allowed them to see the different protein-glycan preferences and started to look at the shapes and structures of the glycan chains to see if there was a consistent pattern for the upper respiratory tract sugars.
Sasisekharan said they were surprised by the diversity of shapes:
"Even though these glycans are all linked the same way chemically, they have very different shapes."
There was however a consistent pattern. Upper respiratory tract glycans tend to be either short and cone-like, or long and umbrella-like.
The hemagglutinin from human-adapted flu viruses attached mainly to the long umbrella glycans that dominate the upper respiratory tract and the bird flu hemagglutinin attached mainly to the short cone glycans that dominate the lower respiratory tract.
The researchers concluded that H5N1 would have to change its hemagglutinin structure so it could latch onto the long umbrella glycans in order to get a foothold in the upper respiratory tract of humans and thereby spread more easily and provoke a pandemic.
Hopefully this new information will alert scientists to keep an eye on how the H5N1 virus evolves, especially in the way it attaches to long glycans.
It will also help to develop new types of therapies for seasonal and pandemic flu, said the researchers.
<em>"Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin."</em>
Aarthi Chandrasekaran, Aravind Srinivasan, Rahul Raman, Karthik Viswanathan, S Raguram, Terrence M Tumpey, V Sasisekharan & Ram Sasisekharan.
<em>Nature Biotechnology</em>, Published online: 06 January 2008.
doi:10.1038/nbt1375
Sources: Journal Abstract, NIH/National Institute of General Medical Sciences press release, Essentials of Glycobiology (1999, Varki, Cummings et al eds).
Written by: Catharine Paddock
Copyright: Medical News Today
Medical News Today
The Flu Vaccine In Powder Form The Answer To A Pandemic?
In recent years, the bird flu virus has caught the attention of all of Western Europe. In 2006 in particular, there was a lot of speculation about a wide-scale flu outbreak, in other words a pandemic. The Dutch government was worried about running short of vaccine, mainly because it has a very short shelf-life. All that could change, says PhD student Jean-Pierre Amorij of the University of Groningen. In his thesis he describes a way of storing flu vaccine in powder form. It can then be stored for at least a year more than enough time to build up national stocks.
Amorij will be awarded his PhD on 4 January 2008. During the past four years he has examined all kinds of methods for long-term storage of the flu vaccine. The answer lay in what is known as freeze drying a protein molecule, such as a vaccine, is extremely quickly frozen between millions of sugar molecules. These molecules bunch together like miniscule balls around the vaccine, so that it can be stored stably in a dried form.
Sugars
Amorij did not use ordinary sugars for the freeze-drying process but special types like inulin and trehalose. It took Amorij eighteen months to find a freeze-drying process that was exactly right. That is painstaking but important work because the vaccine still has to work even after freeze drying. 'The biggest problem was choosing the right freezing speed and the right sugar', says Amorij. But he managed it. The result looks like icing sugar.
No need for a flu jab
Freeze-dried flu vaccine not only has a longer shelf-life, it's also easier to use. You don't need injection needles any more as the powdered vaccine can be swallowed or inhaled. That will save a lot of time if the government has to vaccinate a lot of people very fast during a pandemic. You don't need medical personnel to be present when swallowing or inhaling. Amorij also conducted tests on mice to see whether inhaling or swallowing worked best. 'Inhaling was by far the most effective with the mice,' he says. 'The immune reaction was even more powerful than with an injection.' According to Amorij, the powder is particularly suited to inhalation. It is very light and stays suspended so it can penetrate deep into the lungs. That makes absorption even more efficient.
Application
When the time comes, it thus looks as if all of the Netherlands will be immunised during a pandemic via inhalers. However, according to Amorij the application will take some time yet. 'So far we've only tested it on mice. The tests on people still have to take place. If everything goes well, then that could happen within five years. If there are a few setbacks it could take ten years. One thing is certain, though, it's on its way.'
Curriculum Vitae
Jean-Pierre Amorij (Zaanstad, 1978) studied Pharmacy and Pharmaceutical Engineering at the University of Groningen and was awarded his Pharmacist's diploma in 2003. His PhD thesis at the Faculty of Mathematics and Natural Sciences of the University of Groningen was supervised by Prof. H.W. Frijlink. He conducted his research at the Department of Pharmaceutical Engineering and Biopharmaceutics of the University of Groningen in close cooperation with the Department of Medical Microbiology, Molecular Virology section (Prof. J.C. Wilschut) of the University Medical Center Groningen and the University of Groningen. His thesis is entitled The Development Of Stable Influenza Vaccine Powder Formulations For New Needle Free Dosage Forms.
UNIVERSITY OF GRONINGEN
Po Box 72
http://www.rug.nl
Scientists discover how bird flu jumps to humans
// 07 Jan 2008
A breakthrough has been uncovered by scientists as to how influenza viruses that are carried by birds cross over to humans. This may not only pave the way for a vaccine against avian flu, but also all flu types.
Strains of the flu virus, known as H1 and H3 are the most common to have crossed from animals to humans. These strains are especially efficient in attacking cells in the upper reaches of the respiratory system.
Lethal infections
When they do infect humans it is often with fatal results, as immune systems are unable to recognise and counter the novel pathogen. According to the World Health Organisation (WHO) - of 348 confirmed cases of H5N1 avian flu in the last five years, 216 have died as a result.
There is fear among health officials of an emergence of a new H5 strain that can easily "jump" from birds to humans, potentially unleashing a pandemic on a massive scale.
Scientists’ discoveries
Published in the British journal Nature, findings clarify scientific understanding of how viruses attach themselves to cells inside human lungs.
It has long been known among scientists that whether an influenza strain infects humans depends on the ability of a protein on the surface of the virus, called hemagglutinin, to bind to a sugar receptor in the respiratory tract.
Species jump possible
In humans, these receptors are known as alpha 2-6, and in birds are known as alpha 2-3.
Until recently, scientists believed it was a genetic switch in the virus that allowed it to bind to human rather than bird receptors, making the much-feared "species jump" possible.
But the study, which was led by professor Ram Sasisekharan of Massachusetts Institute of Technology (MIT), says that the big factor is the shape of the sugar receptors in human lung cells.
The human alpha 2-6 receptors have two shapes, one resembling an umbrella, and the other a cone. Researchers have discovered, that to infect humans, flu viruses must bind to the umbrella-shaped receptors.
Improved interventions for seasonal and avian flu
"Now that we know what we are looking for, this could help us not only monitor the bird flu virus, but it can aid in the development of potentially improved therapeutic interventions for both avian and seasonal flu," said Sasisekharan.
world poultry magazine
Shape Of Sugar Molecule Could Be All That Is Stopping Bird Flu Pandemic
US scientists have found that the shape of sugar molecules on cell surfaces in the upper respiratory tract determine how easy it is for influenza viruses to infect humans, and suggest that if the deadly strain of H5N1 bird flu were to adapt a way to bind to this shape of sugar molecule it would spread easily from human to human and provoke a world pandemic.
The study, which is funded by the US National Institutes of Health (NIH) is published in the 6th of January early online issue of <em>Nature Biotechnology</em>. The research team that conducted the study was led by Dr Ram Sasisekharan, of the Massachusetts Institute of Technology in Cambridge.
The deadly strain of H5N1 can only pass from bird to human, because it does not have the ability to spread via coughing and sneezing since the virus does not yet have a way of gaining entry to cells in the human upper respiratory tract.
In this study Sasisekharan and colleagues have discovered what makes it possible for some flu viruses to gain a foothold in the cells lining our noses and throats and why other strains find it more difficult.
Dr Jeremy M. Berg, director of the National Institute of General Medical Sciences (the part of NIH that sponsored the research) said:
"Using an approach that combines experimentation and database analysis, Sasisekharan's team has changed our view of flu viruses and how they must adapt to infect us."
"The work may improve our ability to monitor the evolution of the H5N1 virus and thwart potential outbreaks," he added.
The researchers were interested in a group of sugars called glycans. These are long chain molecules of different shapes that sit on the surfaces of cells and control entry into them. They are like gatekeepers of the cells and only let in agents that have the correct protein (rather like a "pass key"). Some viruses can get in because they have the correct protein to bind with the appropriate glycan.
The flu virus has a pass key called hemagglutinin, a protein that is slightly different for each strain of flu, and latches onto glycans for different cell types. The hemagglutinin of flu viruses that transmit easily between humans are able to bind to the glycans of the cells in the upper respiratory tract (the ones that line the nose and throat).
But the bird flu virus does not have the right type of hemagglutinin to gain access to the upper respiratory tract, it can only bind with glycans on the surfaces of lower respiratory tract cells.
However, Sasisekharan had seen some studies that found bird flu hemagglutinin had sometimes been able to bind to glycans on cells in the upper respiratory tract, and was puzzled as to why the virus didn't spread very well. So he and his team decided to investigate this.
They consulted a database maintained by the Consortium for Functional Glycomics (CFG) which holds information on the interactions between proteins and different types of glycan sugars.
They used the CFG glycan preference array which allowed them to see the different protein-glycan preferences and started to look at the shapes and structures of the glycan chains to see if there was a consistent pattern for the upper respiratory tract sugars.
Sasisekharan said they were surprised by the diversity of shapes:
"Even though these glycans are all linked the same way chemically, they have very different shapes."
There was however a consistent pattern. Upper respiratory tract glycans tend to be either short and cone-like, or long and umbrella-like.
The hemagglutinin from human-adapted flu viruses attached mainly to the long umbrella glycans that dominate the upper respiratory tract and the bird flu hemagglutinin attached mainly to the short cone glycans that dominate the lower respiratory tract.
The researchers concluded that H5N1 would have to change its hemagglutinin structure so it could latch onto the long umbrella glycans in order to get a foothold in the upper respiratory tract of humans and thereby spread more easily and provoke a pandemic.
Hopefully this new information will alert scientists to keep an eye on how the H5N1 virus evolves, especially in the way it attaches to long glycans.
It will also help to develop new types of therapies for seasonal and pandemic flu, said the researchers.
<em>"Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin."</em>
Aarthi Chandrasekaran, Aravind Srinivasan, Rahul Raman, Karthik Viswanathan, S Raguram, Terrence M Tumpey, V Sasisekharan & Ram Sasisekharan.
<em>Nature Biotechnology</em>, Published online: 06 January 2008.
doi:10.1038/nbt1375
Sources: Journal Abstract, NIH/National Institute of General Medical Sciences press release, Essentials of Glycobiology (1999, Varki, Cummings et al eds).
Written by: Catharine Paddock
Copyright: Medical News Today
Medical News Today
The Flu Vaccine In Powder Form The Answer To A Pandemic?
In recent years, the bird flu virus has caught the attention of all of Western Europe. In 2006 in particular, there was a lot of speculation about a wide-scale flu outbreak, in other words a pandemic. The Dutch government was worried about running short of vaccine, mainly because it has a very short shelf-life. All that could change, says PhD student Jean-Pierre Amorij of the University of Groningen. In his thesis he describes a way of storing flu vaccine in powder form. It can then be stored for at least a year more than enough time to build up national stocks.
Amorij will be awarded his PhD on 4 January 2008. During the past four years he has examined all kinds of methods for long-term storage of the flu vaccine. The answer lay in what is known as freeze drying a protein molecule, such as a vaccine, is extremely quickly frozen between millions of sugar molecules. These molecules bunch together like miniscule balls around the vaccine, so that it can be stored stably in a dried form.
Sugars
Amorij did not use ordinary sugars for the freeze-drying process but special types like inulin and trehalose. It took Amorij eighteen months to find a freeze-drying process that was exactly right. That is painstaking but important work because the vaccine still has to work even after freeze drying. 'The biggest problem was choosing the right freezing speed and the right sugar', says Amorij. But he managed it. The result looks like icing sugar.
No need for a flu jab
Freeze-dried flu vaccine not only has a longer shelf-life, it's also easier to use. You don't need injection needles any more as the powdered vaccine can be swallowed or inhaled. That will save a lot of time if the government has to vaccinate a lot of people very fast during a pandemic. You don't need medical personnel to be present when swallowing or inhaling. Amorij also conducted tests on mice to see whether inhaling or swallowing worked best. 'Inhaling was by far the most effective with the mice,' he says. 'The immune reaction was even more powerful than with an injection.' According to Amorij, the powder is particularly suited to inhalation. It is very light and stays suspended so it can penetrate deep into the lungs. That makes absorption even more efficient.
Application
When the time comes, it thus looks as if all of the Netherlands will be immunised during a pandemic via inhalers. However, according to Amorij the application will take some time yet. 'So far we've only tested it on mice. The tests on people still have to take place. If everything goes well, then that could happen within five years. If there are a few setbacks it could take ten years. One thing is certain, though, it's on its way.'
Curriculum Vitae
Jean-Pierre Amorij (Zaanstad, 1978) studied Pharmacy and Pharmaceutical Engineering at the University of Groningen and was awarded his Pharmacist's diploma in 2003. His PhD thesis at the Faculty of Mathematics and Natural Sciences of the University of Groningen was supervised by Prof. H.W. Frijlink. He conducted his research at the Department of Pharmaceutical Engineering and Biopharmaceutics of the University of Groningen in close cooperation with the Department of Medical Microbiology, Molecular Virology section (Prof. J.C. Wilschut) of the University Medical Center Groningen and the University of Groningen. His thesis is entitled The Development Of Stable Influenza Vaccine Powder Formulations For New Needle Free Dosage Forms.
UNIVERSITY OF GRONINGEN
Po Box 72
http://www.rug.nl
Scientists discover how bird flu jumps to humans
// 07 Jan 2008
A breakthrough has been uncovered by scientists as to how influenza viruses that are carried by birds cross over to humans. This may not only pave the way for a vaccine against avian flu, but also all flu types.
Strains of the flu virus, known as H1 and H3 are the most common to have crossed from animals to humans. These strains are especially efficient in attacking cells in the upper reaches of the respiratory system.
Lethal infections
When they do infect humans it is often with fatal results, as immune systems are unable to recognise and counter the novel pathogen. According to the World Health Organisation (WHO) - of 348 confirmed cases of H5N1 avian flu in the last five years, 216 have died as a result.
There is fear among health officials of an emergence of a new H5 strain that can easily "jump" from birds to humans, potentially unleashing a pandemic on a massive scale.
Scientists’ discoveries
Published in the British journal Nature, findings clarify scientific understanding of how viruses attach themselves to cells inside human lungs.
It has long been known among scientists that whether an influenza strain infects humans depends on the ability of a protein on the surface of the virus, called hemagglutinin, to bind to a sugar receptor in the respiratory tract.
Species jump possible
In humans, these receptors are known as alpha 2-6, and in birds are known as alpha 2-3.
Until recently, scientists believed it was a genetic switch in the virus that allowed it to bind to human rather than bird receptors, making the much-feared "species jump" possible.
But the study, which was led by professor Ram Sasisekharan of Massachusetts Institute of Technology (MIT), says that the big factor is the shape of the sugar receptors in human lung cells.
The human alpha 2-6 receptors have two shapes, one resembling an umbrella, and the other a cone. Researchers have discovered, that to infect humans, flu viruses must bind to the umbrella-shaped receptors.
Improved interventions for seasonal and avian flu
"Now that we know what we are looking for, this could help us not only monitor the bird flu virus, but it can aid in the development of potentially improved therapeutic interventions for both avian and seasonal flu," said Sasisekharan.
world poultry magazine
Shape Of Sugar Molecule Could Be All That Is Stopping Bird Flu Pandemic
US scientists have found that the shape of sugar molecules on cell surfaces in the upper respiratory tract determine how easy it is for influenza viruses to infect humans, and suggest that if the deadly strain of H5N1 bird flu were to adapt a way to bind to this shape of sugar molecule it would spread easily from human to human and provoke a world pandemic.
The study, which is funded by the US National Institutes of Health (NIH) is published in the 6th of January early online issue of <em>Nature Biotechnology</em>. The research team that conducted the study was led by Dr Ram Sasisekharan, of the Massachusetts Institute of Technology in Cambridge.
The deadly strain of H5N1 can only pass from bird to human, because it does not have the ability to spread via coughing and sneezing since the virus does not yet have a way of gaining entry to cells in the human upper respiratory tract.
In this study Sasisekharan and colleagues have discovered what makes it possible for some flu viruses to gain a foothold in the cells lining our noses and throats and why other strains find it more difficult.
Dr Jeremy M. Berg, director of the National Institute of General Medical Sciences (the part of NIH that sponsored the research) said:
"Using an approach that combines experimentation and database analysis, Sasisekharan's team has changed our view of flu viruses and how they must adapt to infect us."
"The work may improve our ability to monitor the evolution of the H5N1 virus and thwart potential outbreaks," he added.
The researchers were interested in a group of sugars called glycans. These are long chain molecules of different shapes that sit on the surfaces of cells and control entry into them. They are like gatekeepers of the cells and only let in agents that have the correct protein (rather like a "pass key"). Some viruses can get in because they have the correct protein to bind with the appropriate glycan.
The flu virus has a pass key called hemagglutinin, a protein that is slightly different for each strain of flu, and latches onto glycans for different cell types. The hemagglutinin of flu viruses that transmit easily between humans are able to bind to the glycans of the cells in the upper respiratory tract (the ones that line the nose and throat).
But the bird flu virus does not have the right type of hemagglutinin to gain access to the upper respiratory tract, it can only bind with glycans on the surfaces of lower respiratory tract cells.
However, Sasisekharan had seen some studies that found bird flu hemagglutinin had sometimes been able to bind to glycans on cells in the upper respiratory tract, and was puzzled as to why the virus didn't spread very well. So he and his team decided to investigate this.
They consulted a database maintained by the Consortium for Functional Glycomics (CFG) which holds information on the interactions between proteins and different types of glycan sugars.
They used the CFG glycan preference array which allowed them to see the different protein-glycan preferences and started to look at the shapes and structures of the glycan chains to see if there was a consistent pattern for the upper respiratory tract sugars.
Sasisekharan said they were surprised by the diversity of shapes:
"Even though these glycans are all linked the same way chemically, they have very different shapes."
There was however a consistent pattern. Upper respiratory tract glycans tend to be either short and cone-like, or long and umbrella-like.
The hemagglutinin from human-adapted flu viruses attached mainly to the long umbrella glycans that dominate the upper respiratory tract and the bird flu hemagglutinin attached mainly to the short cone glycans that dominate the lower respiratory tract.
The researchers concluded that H5N1 would have to change its hemagglutinin structure so it could latch onto the long umbrella glycans in order to get a foothold in the upper respiratory tract of humans and thereby spread more easily and provoke a pandemic.
Hopefully this new information will alert scientists to keep an eye on how the H5N1 virus evolves, especially in the way it attaches to long glycans.
It will also help to develop new types of therapies for seasonal and pandemic flu, said the researchers.
<em>"Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin."</em>
Aarthi Chandrasekaran, Aravind Srinivasan, Rahul Raman, Karthik Viswanathan, S Raguram, Terrence M Tumpey, V Sasisekharan & Ram Sasisekharan.
<em>Nature Biotechnology</em>, Published online: 06 January 2008.
doi:10.1038/nbt1375
Sources: Journal Abstract, NIH/National Institute of General Medical Sciences press release, Essentials of Glycobiology (1999, Varki, Cummings et al eds).
Written by: Catharine Paddock
Copyright: Medical News Today
Medical News Today
The Flu Vaccine In Powder Form The Answer To A Pandemic?
In recent years, the bird flu virus has caught the attention of all of Western Europe. In 2006 in particular, there was a lot of speculation about a wide-scale flu outbreak, in other words a pandemic. The Dutch government was worried about running short of vaccine, mainly because it has a very short shelf-life. All that could change, says PhD student Jean-Pierre Amorij of the University of Groningen. In his thesis he describes a way of storing flu vaccine in powder form. It can then be stored for at least a year more than enough time to build up national stocks.
Amorij will be awarded his PhD on 4 January 2008. During the past four years he has examined all kinds of methods for long-term storage of the flu vaccine. The answer lay in what is known as freeze drying a protein molecule, such as a vaccine, is extremely quickly frozen between millions of sugar molecules. These molecules bunch together like miniscule balls around the vaccine, so that it can be stored stably in a dried form.
Sugars
Amorij did not use ordinary sugars for the freeze-drying process but special types like inulin and trehalose. It took Amorij eighteen months to find a freeze-drying process that was exactly right. That is painstaking but important work because the vaccine still has to work even after freeze drying. 'The biggest problem was choosing the right freezing speed and the right sugar', says Amorij. But he managed it. The result looks like icing sugar.
No need for a flu jab
Freeze-dried flu vaccine not only has a longer shelf-life, it's also easier to use. You don't need injection needles any more as the powdered vaccine can be swallowed or inhaled. That will save a lot of time if the government has to vaccinate a lot of people very fast during a pandemic. You don't need medical personnel to be present when swallowing or inhaling. Amorij also conducted tests on mice to see whether inhaling or swallowing worked best. 'Inhaling was by far the most effective with the mice,' he says. 'The immune reaction was even more powerful than with an injection.' According to Amorij, the powder is particularly suited to inhalation. It is very light and stays suspended so it can penetrate deep into the lungs. That makes absorption even more efficient.
Application
When the time comes, it thus looks as if all of the Netherlands will be immunised during a pandemic via inhalers. However, according to Amorij the application will take some time yet. 'So far we've only tested it on mice. The tests on people still have to take place. If everything goes well, then that could happen within five years. If there are a few setbacks it could take ten years. One thing is certain, though, it's on its way.'
Curriculum Vitae
Jean-Pierre Amorij (Zaanstad, 1978) studied Pharmacy and Pharmaceutical Engineering at the University of Groningen and was awarded his Pharmacist's diploma in 2003. His PhD thesis at the Faculty of Mathematics and Natural Sciences of the University of Groningen was supervised by Prof. H.W. Frijlink. He conducted his research at the Department of Pharmaceutical Engineering and Biopharmaceutics of the University of Groningen in close cooperation with the Department of Medical Microbiology, Molecular Virology section (Prof. J.C. Wilschut) of the University Medical Center Groningen and the University of Groningen. His thesis is entitled The Development Of Stable Influenza Vaccine Powder Formulations For New Needle Free Dosage Forms.
UNIVERSITY OF GRONINGEN
Po Box 72
http://www.rug.nl
Scientists discover how bird flu jumps to humans
// 07 Jan 2008
A breakthrough has been uncovered by scientists as to how influenza viruses that are carried by birds cross over to humans. This may not only pave the way for a vaccine against avian flu, but also all flu types.
Strains of the flu virus, known as H1 and H3 are the most common to have crossed from animals to humans. These strains are especially efficient in attacking cells in the upper reaches of the respiratory system.
Lethal infections
When they do infect humans it is often with fatal results, as immune systems are unable to recognise and counter the novel pathogen. According to the World Health Organisation (WHO) - of 348 confirmed cases of H5N1 avian flu in the last five years, 216 have died as a result.
There is fear among health officials of an emergence of a new H5 strain that can easily "jump" from birds to humans, potentially unleashing a pandemic on a massive scale.
Scientists’ discoveries
Published in the British journal Nature, findings clarify scientific understanding of how viruses attach themselves to cells inside human lungs.
It has long been known among scientists that whether an influenza strain infects humans depends on the ability of a protein on the surface of the virus, called hemagglutinin, to bind to a sugar receptor in the respiratory tract.
Species jump possible
In humans, these receptors are known as alpha 2-6, and in birds are known as alpha 2-3.
Until recently, scientists believed it was a genetic switch in the virus that allowed it to bind to human rather than bird receptors, making the much-feared "species jump" possible.
But the study, which was led by professor Ram Sasisekharan of Massachusetts Institute of Technology (MIT), says that the big factor is the shape of the sugar receptors in human lung cells.
The human alpha 2-6 receptors have two shapes, one resembling an umbrella, and the other a cone. Researchers have discovered, that to infect humans, flu viruses must bind to the umbrella-shaped receptors.
Improved interventions for seasonal and avian flu
"Now that we know what we are looking for, this could help us not only monitor the bird flu virus, but it can aid in the development of potentially improved therapeutic interventions for both avian and seasonal flu," said Sasisekharan.
world poultry magazine
Shape Of Sugar Molecule Could Be All That Is Stopping Bird Flu Pandemic
US scientists have found that the shape of sugar molecules on cell surfaces in the upper respiratory tract determine how easy it is for influenza viruses to infect humans, and suggest that if the deadly strain of H5N1 bird flu were to adapt a way to bind to this shape of sugar molecule it would spread easily from human to human and provoke a world pandemic.
The study, which is funded by the US National Institutes of Health (NIH) is published in the 6th of January early online issue of <em>Nature Biotechnology</em>. The research team that conducted the study was led by Dr Ram Sasisekharan, of the Massachusetts Institute of Technology in Cambridge.
The deadly strain of H5N1 can only pass from bird to human, because it does not have the ability to spread via coughing and sneezing since the virus does not yet have a way of gaining entry to cells in the human upper respiratory tract.
In this study Sasisekharan and colleagues have discovered what makes it possible for some flu viruses to gain a foothold in the cells lining our noses and throats and why other strains find it more difficult.
Dr Jeremy M. Berg, director of the National Institute of General Medical Sciences (the part of NIH that sponsored the research) said:
"Using an approach that combines experimentation and database analysis, Sasisekharan's team has changed our view of flu viruses and how they must adapt to infect us."
"The work may improve our ability to monitor the evolution of the H5N1 virus and thwart potential outbreaks," he added.
The researchers were interested in a group of sugars called glycans. These are long chain molecules of different shapes that sit on the surfaces of cells and control entry into them. They are like gatekeepers of the cells and only let in agents that have the correct protein (rather like a "pass key"). Some viruses can get in because they have the correct protein to bind with the appropriate glycan.
The flu virus has a pass key called hemagglutinin, a protein that is slightly different for each strain of flu, and latches onto glycans for different cell types. The hemagglutinin of flu viruses that transmit easily between humans are able to bind to the glycans of the cells in the upper respiratory tract (the ones that line the nose and throat).
But the bird flu virus does not have the right type of hemagglutinin to gain access to the upper respiratory tract, it can only bind with glycans on the surfaces of lower respiratory tract cells.
However, Sasisekharan had seen some studies that found bird flu hemagglutinin had sometimes been able to bind to glycans on cells in the upper respiratory tract, and was puzzled as to why the virus didn't spread very well. So he and his team decided to investigate this.
They consulted a database maintained by the Consortium for Functional Glycomics (CFG) which holds information on the interactions between proteins and different types of glycan sugars.
They used the CFG glycan preference array which allowed them to see the different protein-glycan preferences and started to look at the shapes and structures of the glycan chains to see if there was a consistent pattern for the upper respiratory tract sugars.
Sasisekharan said they were surprised by the diversity of shapes:
"Even though these glycans are all linked the same way chemically, they have very different shapes."
There was however a consistent pattern. Upper respiratory tract glycans tend to be either short and cone-like, or long and umbrella-like.
The hemagglutinin from human-adapted flu viruses attached mainly to the long umbrella glycans that dominate the upper respiratory tract and the bird flu hemagglutinin attached mainly to the short cone glycans that dominate the lower respiratory tract.
The researchers concluded that H5N1 would have to change its hemagglutinin structure so it could latch onto the long umbrella glycans in order to get a foothold in the upper respiratory tract of humans and thereby spread more easily and provoke a pandemic.
Hopefully this new information will alert scientists to keep an eye on how the H5N1 virus evolves, especially in the way it attaches to long glycans.
It will also help to develop new types of therapies for seasonal and pandemic flu, said the researchers.
<em>"Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin."</em>
Aarthi Chandrasekaran, Aravind Srinivasan, Rahul Raman, Karthik Viswanathan, S Raguram, Terrence M Tumpey, V Sasisekharan & Ram Sasisekharan.
<em>Nature Biotechnology</em>, Published online: 06 January 2008.
doi:10.1038/nbt1375
Sources: Journal Abstract, NIH/National Institute of General Medical Sciences press release, Essentials of Glycobiology (1999, Varki, Cummings et al eds).
Written by: Catharine Paddock
Copyright: Medical News Today
Medical News Today
The Flu Vaccine In Powder Form The Answer To A Pandemic?
In recent years, the bird flu virus has caught the attention of all of Western Europe. In 2006 in particular, there was a lot of speculation about a wide-scale flu outbreak, in other words a pandemic. The Dutch government was worried about running short of vaccine, mainly because it has a very short shelf-life. All that could change, says PhD student Jean-Pierre Amorij of the University of Groningen. In his thesis he describes a way of storing flu vaccine in powder form. It can then be stored for at least a year more than enough time to build up national stocks.
Amorij will be awarded his PhD on 4 January 2008. During the past four years he has examined all kinds of methods for long-term storage of the flu vaccine. The answer lay in what is known as freeze drying a protein molecule, such as a vaccine, is extremely quickly frozen between millions of sugar molecules. These molecules bunch together like miniscule balls around the vaccine, so that it can be stored stably in a dried form.
Sugars
Amorij did not use ordinary sugars for the freeze-drying process but special types like inulin and trehalose. It took Amorij eighteen months to find a freeze-drying process that was exactly right. That is painstaking but important work because the vaccine still has to work even after freeze drying. 'The biggest problem was choosing the right freezing speed and the right sugar', says Amorij. But he managed it. The result looks like icing sugar.
No need for a flu jab
Freeze-dried flu vaccine not only has a longer shelf-life, it's also easier to use. You don't need injection needles any more as the powdered vaccine can be swallowed or inhaled. That will save a lot of time if the government has to vaccinate a lot of people very fast during a pandemic. You don't need medical personnel to be present when swallowing or inhaling. Amorij also conducted tests on mice to see whether inhaling or swallowing worked best. 'Inhaling was by far the most effective with the mice,' he says. 'The immune reaction was even more powerful than with an injection.' According to Amorij, the powder is particularly suited to inhalation. It is very light and stays suspended so it can penetrate deep into the lungs. That makes absorption even more efficient.
Application
When the time comes, it thus looks as if all of the Netherlands will be immunised during a pandemic via inhalers. However, according to Amorij the application will take some time yet. 'So far we've only tested it on mice. The tests on people still have to take place. If everything goes well, then that could happen within five years. If there are a few setbacks it could take ten years. One thing is certain, though, it's on its way.'
Curriculum Vitae
Jean-Pierre Amorij (Zaanstad, 1978) studied Pharmacy and Pharmaceutical Engineering at the University of Groningen and was awarded his Pharmacist's diploma in 2003. His PhD thesis at the Faculty of Mathematics and Natural Sciences of the University of Groningen was supervised by Prof. H.W. Frijlink. He conducted his research at the Department of Pharmaceutical Engineering and Biopharmaceutics of the University of Groningen in close cooperation with the Department of Medical Microbiology, Molecular Virology section (Prof. J.C. Wilschut) of the University Medical Center Groningen and the University of Groningen. His thesis is entitled The Development Of Stable Influenza Vaccine Powder Formulations For New Needle Free Dosage Forms.
UNIVERSITY OF GRONINGEN
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http://www.rug.nl
Scientists discover how bird flu jumps to humans
// 07 Jan 2008
A breakthrough has been uncovered by scientists as to how influenza viruses that are carried by birds cross over to humans. This may not only pave the way for a vaccine against avian flu, but also all flu types.
Strains of the flu virus, known as H1 and H3 are the most common to have crossed from animals to humans. These strains are especially efficient in attacking cells in the upper reaches of the respiratory system.
Lethal infections
When they do infect humans it is often with fatal results, as immune systems are unable to recognise and counter the novel pathogen. According to the World Health Organisation (WHO) - of 348 confirmed cases of H5N1 avian flu in the last five years, 216 have died as a result.
There is fear among health officials of an emergence of a new H5 strain that can easily "jump" from birds to humans, potentially unleashing a pandemic on a massive scale.
Scientists’ discoveries
Published in the British journal Nature, findings clarify scientific understanding of how viruses attach themselves to cells inside human lungs.
It has long been known among scientists that whether an influenza strain infects humans depends on the ability of a protein on the surface of the virus, called hemagglutinin, to bind to a sugar receptor in the respiratory tract.
Species jump possible
In humans, these receptors are known as alpha 2-6, and in birds are known as alpha 2-3.
Until recently, scientists believed it was a genetic switch in the virus that allowed it to bind to human rather than bird receptors, making the much-feared "species jump" possible.
