H5N1 Avian Flu news thread

[Preciouslife1]

Crucell Discovers Human Monoclonal Antibodies for the Prevention and Treatment of the Avian Flu Virus; The Antibody Provides Immediate Protection and Neutralizes the Broadest Range of H5N1 Strains


LEIDEN, NETHERLANDS--(MARKET WIRE)--Sep 27, 2007 -- Dutch biotechnology company Crucell N.V. (Euronext, NASDAQ: CRXL, Swiss Exchange: CRX) today announced the discovery of a set of human monoclonal antibodies against H5N1. These results, demonstrating the potential of human monoclonal antibodies for pandemic preparedness, were presented today at the 5th International Bird Flu Summit held in Las Vegas, Nevada.

A total of twenty one human monoclonal antibodies were discovered. These were found to be able to neutralize the H5N1 virus of avian influenza, which currently presents a global threat. The most potent of the antibodies was shown to neutralize the broadest range of H5N1 strains that have emerged between 1997 and 2004. This antibody may therefore provide a powerful tool in pandemic preparedness. In addition, this antibody prevents flu, in pre-clinical models, when given twenty four hours before a challenge with a lethal dose of highly pathogenic H5N1 virus. When given three days after infection, it also was shown to prevent death and cure the disease.

"Our discovery of potent human monoclonal antibodies against a number of different H5N1 pandemic flu types, provide proof of concept that antibodies are a serious alternative to vaccination or antiviral treatment", said Dr. Jaap Goudsmit, Chief Scientific Officer of Crucell. "What is most encouraging is the fact that these antibodies are not only able to prevent infection, but also open the possibility to treat infected individuals. Treatment with this antibody provides an instantaneous antiviral response, which is an advantage over the delayed immune response after (prepandemic) vaccination."

The set of monoclonal antibodies, which was produced by Crucell researchers using phage display and Crucell PER.C6® technology, showed the potential to neutralize distinct H5N1 viruses, A/Vietnam/11994/04, A/Hong Kong/213/03 and A/Hong Kong/156/97. The antibodies apparently recognize a part of the viral membrane protein that is present among all H5N1 viruses tested. The most potent neutralizing antibody was tested in pre-clinical models for the ability to protect against infection with the highly pathogenic A/Hong Kong/97 H5N1 virus and was also tested for its ability to stop the development of the disease caused by this virus. When the monoclonal antibody was given in a pre-clinical model, one day prior to infection with the H5N1 virus, it resulted in full protection against infection. Treatment with the antibody up to three days after infection, resulted in 100% survival and cure of the disease.

About Pandemic Influenza

Influenza is a highly infectious virus which spreads easily from person to person. In a pandemic, a new and more virulent virus infectious for humans arises with the potential to cause severe disease and high mortality. H5N1 Viruses isolated from wild and domestic birds and from humans since the outbreaks in Hong Kong separate in distinct genetic groups (clade and subclades) of closely related viruses. Clade 1 virus circulated in Cambodia, Thailand and Viet Nam and caused infections in humans in 2004 and 2005. Clade 2 viruses circulated in China and Indonesia in 2003 -2004 and spread to the Middle East, Africa and Europe in 2005 and 2006.

[Preciouslife1]

H5N1 Bird Flu Virus Strain Can Pass Through Placenta To Unborn Fetus



The H5N1 avian influenza virus strain can infect an unborn fetus by passing through the placenta. The virus can also infect other adult organs apart from the lungs, according to an article in The Lancet published this week.

Professor Jiang Gu, Peking University, Beijing, China and team examined post-mortem tissue samples of two adults, one male and one pregnant female. They also examined the dead fetus of the pregnant female. Their aim was to find out how H5N1 affects the organs of the human body.

"A pandemic outbreak of human infection with avian H5N1 currently poses a potentially serious health threat worldwide - little is known about the specific effects in organs and cells targeted by the virus," explain the authors.

The scientists found viral genetic material and antigens in some trachea cells, the lungs, the T cells of the lymph node, brain neurons, and cells of the placenta. They detected viral genetic material in the intestinal mucosa, but ho H5N1 antigens.

In the fetus they detected antigens and genetic material in the lungs, circulating cells of the immune system, and liver cells.

"This study has shown the capacity for human vertical transmission of the H5N1 virus..(this) warrants careful investigation, since maternal infections with common human influenza virus are generally thought not to infect the fetus. We have shown that H5N1 virus spreads beyond the lungs..these newly obtained data are important in the clinical, pathological and epidemiological investigation of human H5N1 infection, and have implications for public-health and health care providers," the authors wrote.

"Speculation about the fate of the fetus if the mother survived is interesting. With the development of antibodies in the mother and their transplacental crossing into the fetus, pathological lesions in the fetus may result," Dr Wai Fu Ng, Department of Pathology, Yan Chai Hospital, Hong Kong, China and Dr Ka Fai To, Ki ka Shing Institute of Health Science, Hong Kong, China, wrote in an accompanying Comment.

http://www.thelancet.com

[Preciouslife1]

New Avian Influenza Biosensor Detects Virus In Minutes And Is Field-Deployable



Quick identification of avian influenza infection in poultry is critical to controlling outbreaks, but current detection methods can require several days to produce results.

A new biosensor developed at the Georgia Tech Research Institute (GTRI) can detect avian influenza in just minutes. In addition to being a rapid test, the biosensor is economical, field-deployable, sensitive to different viral strains and requires no labels or reagents.

"We can do real-time monitoring of avian influenza infections on the farm, in live-bird markets or in poultry processing facilities," said Jie Xu, a research scientist in GTRI's Electro-Optical Systems Laboratory (EOSL).

Worldwide, there are many strains of avian influenza virus that cause varying degrees of clinical symptoms and illness. In the United States, outbreaks of the disease -- primarily spread by migratory aquatic birds -- have plagued the poultry industry for decades with millions of dollars in losses. The only way to stop the spread of the disease is to destroy all poultry that may have been exposed to the virus.

A virulent strain of avian influenza (H5N1) has begun to threaten not only birds but humans, with more than 300 infections and 200 deaths reported to the World Health Organization since 2003. Looming is the threat of a pandemic, such as the 1918 Spanish flu that killed about 40 million people, health officials say.

"With so many different virus subtypes, our biosensor's ability to detect multiple strains of avian influenza at the same time is critical," noted Xu.

To test the biosensor, the researchers assessed its ability to detect two avian influenza strains that previously infected poultry. The results showed that a solution containing very few virus particles could be detected by the sensor.

Xu tested a third strain of the virus as a control. When the sensor coating was modified to collect only the other two strains, the control strain was not detected even at high concentrations. Results of this study were published online in August in the journal Analytical and Bioanalytical Chemistry and will be included in journal's print edition on October 16. The work was funded by the U.S. Department of Agriculture's (USDA) Agricultural Research Service (ARS) and the Georgia Research Alliance.

"The technology that Georgia Tech developed with our help has many advantages over commercially available tests -- improved sensitivity, rapid testing and the ability to identify different strains of the influenza virus simultaneously," said David Suarez, a collaborator on the project and research leader of exotic and emerging avian viral diseases in ARS' Southeast Poultry Research Laboratory in Athens, Ga. Suarez is providing antibodies and test samples for GTRI's research.

The biosensor is coated with antibodies specifically designed to capture a protein located on the surface of the viral particle. For this study, the researchers evaluated the sensitivity of three unique antibodies to detect avian influenza virus.

The sensor utilizes the interference of light waves, a concept called interferometry, to precisely determine how many virus particles attach to the sensor's surface. More specifically, light from a laser diode is coupled into an optical waveguide through a grating and travels under one sensing channel and one reference channel.

Researchers coat the sensing channel with the specific antibodies and coat the reference channel with non-specific antibodies. Having the reference channel minimizes the impact of non-specific interactions, as well as changes in temperature, pH and mechanical motion. Non-specific binding should occur equally to both the test and reference channels and thus not affect the test results.

An electromagnetic field associated with the light beams extends above the waveguides and is very sensitive to the changes caused by antibody-antigen interactions on the waveguide surface. When a liquid sample passes over the waveguides, any binding that occurs on the top of a waveguide because of viral particle attachment causes water molecules to be displaced. This causes a change in the velocity of the light traveling through the waveguide.

At the end of the waveguide, the light beams from the sensing and reference channels are combined to create an interference pattern. The pattern of alternating dark and light vertical stripes, or fringes, is imaged on a simple detector. By doing a mathematical Fourier transform, the researchers determine the degree to which the fringe patterns are in or out of step with each other, known as phase shift. This phase shift tells the amount of virus bound to the surface.

"The fringe pattern doesn't look like it changes in the image, but with math we find out the speed of the light in the test channel changed creating this phase change," explained Xu.

Current methods of identifying infected birds include virus isolation, real-time reverse transcriptase polymerase chain reaction (RRT-PCR) and antigen capture immunoassays. Virus isolation is a sensitive technique, but typically requires five to seven days for testing. RRT-PCR is commonly available in veterinary diagnostic laboratories, but requires expensive equipment and appropriate laboratory facilities. RT-PCR can take as little as three hours to get test results, but routine surveillance samples are more often processed in 24 hours. The antigen capture immunoassays can provide rapid test results, but suffer from low sensitivity and high cost.

Beyond the waveguide sensor, the only additional external components required for field-testing with GTRI's biosensor include a sample-delivery device (peristaltic pump), a data collection laptop computer and a swab taken from a potentially infected bird. Power is supplied by a nine volt battery and USB connection. The waveguides can be cleaned and reused dozens of times, decreasing the per-test cost of the chip fabrication.

Xu and Suarez are currently working together to test new unique antibodies with the biosensor and to test different strains. In addition, Xu is reducing the size of the prototype device to be about the size of a lunchbox and making the computer analysis software more user-friendly so that it can be field-tested in two years.

"We are continuing our collaboration and have provided additional money to Georgia Tech to move the project along faster," added Suarez. "Since this technology is already set up so that you can use multiple antibodies to detect different influenza subtypes, we are going to extend the work to include the H5 subtype."

----------------------------

[Preciouslife1]

Avian Influenza Detected In Saskatchewan, Canada


pathogenic H7N3 avian influenza has been detected in a commercial poultry operation in Saskatchewan, the Canadian Food Inspection Agency (CFIA) announced recently. This virus is not the same as the strain circulating in Asia, Africa and Europe, which has been associated with human illness. H7N3 is not normally associated with serious human illness.

Avian influenza viruses do not pose risks to food safety when poultry and poultry products are properly handled and cooked. In this case, the affected birds were not destined for immediate slaughter and were not producing eggs for human consumption.

All birds on the infected premises will be humanely euthanized and disposed of in accordance with provincial regulations and internationally accepted disease control guidelines. Normally, birds on any commercial operations within one kilometre of an infected premises would also be destroyed, but early information indicates that no such operations are present in the immediate area.

Once all birds have been removed, the CFIA will oversee the cleaning and disinfection of the barns, vehicles, equipment and tools to eliminate any infectious material that may remain.

To limit any potential virus spread, the CFIA will apply restrictions on the movement of poultry and poultry products within three kilometres of the infected premises. As an additional safeguard, any poultry operations within ten kilometres of the infected premises will be closely and regularly monitored for signs of illness.

The CFIA is investigating the recent movement of birds, bird products and equipment onto and off of the property. Through this activity, additional cases of infection may be detected.

The CFIA's actions are consistent with internationally recognized animal health guidelines and the CFIA's established avian influenza response protocols.

It may be difficult to identify the source of the virus, but the possibility of exposure to wild waterfowl-which are the natural hosts for the virus-cannot be discounted. Poultry owners are urged to take an active role in protecting their flocks by keeping them away from wild birds and areas frequented by wild birds.

Under the Health of Animals Act, the CFIA has authority to compensate producers for animals ordered destroyed during disease responses. The producer might also be eligible for assistance under other Government of Canada or provincial programs.

The Province of Saskatchewan and industry are actively collaborating in this response effort. The CFIA wishes to acknowledge the responsible actions of the owner, who reported signs of illness at the earliest possible moment. This commitment to animal health protection has maximized the Agency's ability to contain and eliminate this situation as quickly as possible.

New information emerging from the CFIA's activities will be provided to the public as it becomes available.

Canadian Food Inspection Agency

[Preciouslife1]

Mechanisms By Which H5N1 Causes Disease Shown By New Research



H5N1 influenza, also known as avian influenza, is considered a major global threat to human health, with high fatality rates. While little had been known about the specific effects of H5N1 on organs and cells targeted by the virus, researchers at Beijing University, Columbia University Mailman School of Public Health, and SUNY Downstate report in the September 29, 2007 issue of the Lancet detailed studies of human H5N1 victims that shed light on the anatomic distribution of the virus and its pathogenesis. Using a combination of molecular and protein labeling techniques, the authors found that H5N1 is present in the gastrointestinal tract and immune and central nervous systems, as well as the respiratory tract. In one patient, virus was transmitted across the placenta to the fetus.

The newly obtained data are important in the clinical, pathological, and epidemiological investigations of human H5N1 infection, and have widespread implications for public-health and healthcare providers. Although there has been considerable progress in studying the virus itself, and in developing surveillance networks, diagnostic tests, drugs and vaccines, only limited information has been obtained concerning the mechanisms by which H5N1 causes disease.

H5N1 infections initially seemed to be restricted to the lungs, but later reports have suggested that influenza A H5N1 could disseminate beyond the lungs. Lung damage is severe and disproportionate to the number of cells that are infected, with macrophages and T-cells targeted for infection. These latest findings indicate that lung damage is not due to virus replication alone and support the hypothesis that indirect effects, such as soluble factors known as cytokine and chemokines, are important.

According to the paper's senior author W. Ian Lipkin, MD, director of the Center for Infection and Immunity at Columbia University Mailman School of Public Health and professor of Epidemiology, Neurology, and Pathology at Columbia, "This is the first major paper from the Beijing Infectious Disease Center, established in the aftermath of SARS by Beijing University, the Chinese Ministry of Science and Technology (the CDC of China), and the Mailman School of Public Health. The work helps us to understand H5N1's high fatality rate, as well as serving as model for global collaboration in the field of emerging infectious diseases."

[Preciouslife1]

New bird flu strain dangerous to humans

LONDON, Oct. 7 (UPI) -- A new strain of the bird flu virus spreading around the world is more infectious to humans, a study lead by a U.S. researcher has found.
Led by Yoshihiro Kawaoka of the University of Wisconsin-Madison, the new study found the H5N1 virus has apparently mutated into a new strain that increases the risk of a human pandemic due to its increased level of communicability, The Independent said Saturday.
Kawaoka said the new strain does not represent a fully pandemic strain of the virus, but warned the mutated virus has been found in both Europe and Africa.
"The viruses circulating in Europe and Africa all have this mutation," the doctor said. "So they are the ones that are closer to human-like flu."
Since the virus was first reported in 2003, 329 people worldwide have been infected according to World Health Organization figures.
Those figures also show that of those infected during that time period, 201 have died as a result.
The British newspaper said health groups worldwide have prepared for a possible pandemic by collecting anti-flu drugs and preparing emergency treatment plans.

[Preciouslife1]

Researchers Identify Key Step Bird Flu Virus Takes To Spread Readily In Humans

Since it first appeared in Hong Kong in 1997, the H5N1 avian flu virus has been slowly evolving into a pathogen better equipped to infect humans. The final form of the virus, biomedical researchers fear, will be a highly pathogenic strain of influenza that spreads easily among humans. In a new study a team of researchers from the University of Wisconsin-Madison report the identification of a key step the virus must take to facilitate the easy transmission of the virus from person to person. The study, published today in the journal PLoS Pathogens, details how a team of researchers led by virologist Yoshihiro Kawaoka of the UW-Madison School of Veterinary Medicine has identified a single change in a viral protein that facilitates the virus' ability to infect the cells of the upper respiratory system in mammals. This adaptation could allow the virus to infect a wider range of cell types and spread more easily, potentially setting the stage for a flu pandemic.

"The viruses that are in circulation now are much more mammalian-like than the ones circulating in 1997," says Kawaoka, an internationally recognized authority on influenza. "The viruses that are circulating in Africa and Europe are the ones closest to becoming a human virus." There are other yet-to-be-determined changes required for the virus to become a human pathogen of pandemic proportions, Kawaoka explains, but establishing itself in the upper respiratory system is necessary as that enables easy transmission of the virus through coughing and sneezing. As its name implies, bird flu first arises in chickens and other birds. Humans and other animals in close contact with the birds may become infected as the virus begins to adapt to new host animals, a process that may take years as small changes accumulate. Over time, an avian virus may gather enough genetic change to spread easily, as experts believe was the case with the 1918 Spanish flu, an event that killed at least 30 million people worldwide.

To date, more than 250 H5N1 human infections worldwide have been reported. Of those, more than 150 have been fatal, but so far efficient human-to-human transmission has not occurred. Most infections have occurred as a result of humans being in close contact with birds that have the virus, such as chickens.

According to Kawaoka, the avian virus can reside in the lungs of humans and other mammals as the cells of the lower respiratory system have receptors that enable the virus to establish itself. Temperatures in the lungs are also higher and thus more amenable to the efficient growth of the virus.

The new study involved two different viruses isolated from a single patient -- one from the lungs, the other from the upper respiratory system. The virus from the upper respiratory system exhibited a single amino acid change in one of the key proteins for amplification of influenza virus genes.

The single change identified by the Wisconsin study, Kawaoka says, promotes better virus replication at lower temperatures, such as those found in the upper respiratory system, and in a wider range of cell types.

"This change is needed, but not sufficient," Kawaoka explains. "There are other viral factors needed to cause a viral pandemic" strain of bird flu. However, Kawaoka and other flu researchers are convinced it is only a matter of time, as more humans and other animals are exposed to the virus, before H5N1 virus takes those steps and evolves into a virus capable of causing a pandemic.

In addition to Kawaoka, authors of the new PLoS Pathogens study include Masato Hatta, Yasuko Hatta, Jin Hyun Kim, Shinji Watanabe of the UW-Madison School of Veterinary Medicine; Kyoko Shinya of Japan's Tottori University; Tung Nguyen of the Vietnamese National Centre for Veterinary Diagnostics; Phuong Song Lien of the Vietnam Veterinary Association; and Quynh Mai Le of the Vietnamese National Institute of Hygiene and Epidemiology. The work was funded by grants from the U.S. National Institutes of Health and the Japan Science and Technology Agency.

CITATION: Noda T, Ebihara H, Muramoto Y, Fujii K, Takada A, et al. (2006) Assembly and budding of Ebolavirus. PLoS Pathog 2(9): e99. DOI: 10.1371/journal.ppat.0020099

[Preciouslife1]

Grid Computing Offers New Hope In Race Against Bird Flu



Last month a collaboration of European and Asian researchers launched a new attack against the deadly bird flu virus, harnessing the combined power of more than 40,000 computers across 45 countries to boost the pace of anti viral drug discovery.

Called Enabling Grids for E-sciencE, the computing grid connects ordinary PCs to form a super sized supercomputer that is being used during this challenge to analyse the potential of more than 500,000 drug like molecules over the next few weeks.

This effort comes as new data released last week by Peking University in Beijing, China, shows that the H5N1 bird flu virus can pass through the placenta of pregnant women to the unborn fetus, and can infect organs other than the lungs in adults. A rapid response to any pandemic outbreak of the virus would be essential to its control.

Dr Ying-Ta Wu, biologist at the Genomics Research Center of the Academia Sinica, says computing grids like EGEE are the fastest and cheapest way to discover new drug leads.

"We are using EGEE to find new molecules that can inhibit the activities of the influenza virus," Dr Ying-Ta Wu explains "During previous challenges using the EGEE grid we discovered about 200 molecules with the potential to become drugs against bird flu."

The EGEE computing grid powers drug discovery software that allows researchers to compute the probability that a drug-like molecule will dock with active sites on the virus and thus inhibit its action. Using the results of such in silico screening, researchers can predict which compounds are most effective at blocking the virus. This accelerates the discovery of novel potent inhibitors by minimising the non-productive trial-and-error approach in a laboratory.

"Asian flu remains a threat to world health and we are well aware that any pandemic could quickly spread throughout Europe" said Viviane Reding, European Commissioner for Information Society and Media. "I am pleased that the European project EGEE has found such an important application for computer grid technology as speeding-up drug discovery against neglected and emerging diseases. Collaboration between Europe and Asia is essential if we are to address world wide threats to public health".

At the EGEE'07 conference in Budapest, Ulf Dahlsten, Director of "Emerging Technologies and Infrastructures" in the Information Society and Media Directorate General of the European Commission, used the example of EGEE's success with bird flu to illustrate the potential contributions of e-Infrastructures to science. "Computer Grids have achieved a productivity increase of more than 6000% in the identification of potential new drugs" he said. "300,000 molecules have already been screened using the EGEE grid. Of these, 123 potential inhibitors were identified, of which seven have now been shown to act as inhibitors in in-vitro laboratory tests. This is a six percent success rate compared to typical values of around 0.1 percent using classical drug discovery methods."

EGEE-ENABLING GRIDS FOR E-SCIENCE
CERN
1211 Geneva 23
http://www.eu-egee.org

[Preciouslife1]

Avian flu: Beyond respiration

Felix Cheung
Abstract

The avian flu virus H5N1 infects the respiratory tract and spreads to other organs in the human body

Original article citation

Gu, J. et al. H5N1 infection of the respiratory tract and beyond: A molecular pathology study. Lancet 370, 1137–1145 (2007).
Introduction

© (2007) Elsevier

Avian flu H5N1 is an emerging infectious disease that can cause respiratory failure and death in humans. Although the H5N1 virus infects the lungs initially, studies have suggested that it could also spread to other organs in the body. Research by Jiang Gu at Peking University in Beijing1 and co-workers supports this suggestion.
Using newly developed molecular techniques, the researchers studied post-mortem tissues of two adults infected with H5N1 (a man and a pregnant woman) and a fetus carried by the woman. In the adults, they detected genomic sequences and antigens of the virus in cells of the lungs, the trachea (windpipe), lymph nodes, brain and, in the woman, also in the placenta. In addition, they detected genomic sequences but no antigen of the virus in intestinal tissues. Therefore, H5N1 not only infects the respiratory tract, but also spreads to other non-respiratory organs.
In the fetus, the researchers detected genomic sequences and antigens of the virus in cells of the lungs and the liver (see image), indicating that H5N1 could also be transmitted from the mother to the fetus across the placenta.
The findings are important for the investigation of human H5N1 infection, and have implications for public-health and health-care providers.
The authors of this work are from:
Infectious Disease Centre, Department of Pathology, School of Basic Medical Sciences, People's Hospital, Neuroscience Research Institute, Peking University, Beijing, China; College of Veterinary Medicine, China Agricultural University, Beijing, China; Department of Pathology, State University of New York, Health Science Center at Brooklyn, New York City, New York, USA; Mailman School of Public Health, Columbia University, New York City, New York, USA.

Reference

1. Gu, J. et al. H5N1 infection of the respiratory tract and beyond: A molecular pathology study. Lancet 370, 1137–1145 (2007).

[Preciouslife1]

Vical Demonstrates Dose-sparing Of Protein-based H5N1 Influenza Vaccine With Vaxfectin(TM) Adjuvant

http://www.medicalnewstoday.com/articles/85081.php

Vical Incorporated (Nasdaq: VICL) announced that data from a study in mice demonstrated the potential of its patented Vaxfectin(TM) adjuvant to be used as a dose-sparing agent with a protein-based H5N1 pandemic influenza vaccine currently stockpiled by the U.S. government. Dose-sparing ability could be critical in extending limited vaccine supplies to protect the greatest number of people in the event of a pandemic influenza outbreak. Alain Rolland, Pharm.D., Ph.D., Vical's Senior Vice President of Product Development, presented the data at the World Vaccine Congress (Lyon, France, October 8 - 10).

Vaxfectin(TM)-formulated Measles DNA Vaccine

The company also announced that a measles DNA vaccine formulated with the company's Vaxfectin(TM) adjuvant elicited sustained protective levels of neutralizing antibodies in infant (6 - 10 week old) nonhuman primates confirmed by complete protection following challenge one year after intradermal vaccination, with no clinical signs of disease and no culturable virus after challenge.
In May, the company announced similar results in juvenile (1 - 2 year old) nonhuman primates. Both measles studies were conducted in collaboration with Diane E. Griffin, M.D., Ph.D., Alfred and Jill Sommer Professor and Chair of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, under a grant from the Bill and Melinda Gates Foundation.

"We continue to expand the database demonstrating the dose-sparing and immunogenicity-enhancing capabilities of our Vaxfectin(TM) adjuvant," said Dr. Rolland, "as well as its potential safety and tolerability advantages. Our lead DNA vaccine candidate against H5N1 influenza, formulated with Vaxfectin(TM), provided 100% protection in mice and ferrets against lethal challenges, and is currently in Phase 1 human testing. We are encouraged by the recent influenza and measles data, and look forward to further evaluation of Vaxfectin(TM)."

Study Details

In the recent influenza study, mice were vaccinated with U.S. government-supplied H5N1 vaccine (rgA/Vietnam/1203/2004 - BEI Resources, Catalog No. NR-4143), with or without the Vaxfectin(TM) adjuvant, and evaluated for antibody responses by Enzyme-Linked ImmunoSorbent Assay (ELISA). After a single injection, the Vaxfectin(TM)-formulated vaccine yielded five-fold higher antibody responses at the same dose as the unformulated vaccine, and comparable or better antibody responses at one-third the dose of unformulated vaccine. After a second injection, the Vaxfectin(TM)-formulated vaccine yielded nine-fold higher antibody responses at the same dose as the unformulated vaccine, and five-fold better antibody responses at one-third the dose of the unformulated vaccine.

In an earlier influenza study, the company demonstrated that the Vaxfectin(TM) adjuvant significantly boosted the immune response to a protein-based seasonal influenza vaccine. Mice were vaccinated with trivalent inactivated influenza vaccine (Sanofi-Pasteur Fluzone(R) 2005-2006 Formula commercial product), with or without the Vaxfectin(TM) adjuvant, and evaluated for antibody responses through hemagglutination inhibition (HI) titers. The Vaxfectin(TM)-formulated vaccine yielded significantly higher antibody responses than the unformulated vaccine at the same dose as well as a dose-sparing effect.

In the recently completed measles study in infant nonhuman primates, neutralizing antibody levels exceeded the accepted protection threshold prior to the second injection at Week 4, peaked at Week 8, and remained above the threshold at least through the 20-week follow-up period. Animals were challenged by intratracheal inoculation after one year, resulting in complete protection of all vaccinated animals. None of the vaccinated animals had disease symptoms or culturable levels of measles virus, in contrast to negative control animals which all had rashes and positive virus cultures. No adverse events related to the vaccination were observed.

About Vical

Vical researches and develops biopharmaceutical products based on its patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases. Potential applications of the company's DNA delivery technology include DNA vaccines for infectious diseases or cancer, in which the expressed protein is an immunogen; cancer immunotherapeutics, in which the expressed protein is an immune system stimulant; and cardiovascular therapies, in which the expressed protein is an angiogenic growth factor. The company is developing certain infectious disease vaccines and cancer therapeutics internally. In addition, the company collaborates with major pharmaceutical companies and biotechnology companies that give it access to complementary technologies or greater resources. These strategic partnerships provide the company with mutually beneficial opportunities to expand its product pipeline and address significant unmet medical needs. Additional information on Vical is available at http://www.vical.com.

This press release contains forward-looking statements subject to risks and uncertainties that could cause actual results to differ materially from those projected, including: whether Vical or others will continue evaluation of Vaxfectin(TM) as an adjuvant for vaccines against influenza or measles; whether Vaxfectin(TM) will be used as a dose-sparing agent with conventional influenza vaccines against seasonal or pandemic influenza strains; whether Vical or others will continue development of the pandemic influenza or measles DNA vaccine candidates; whether H5N1 or other strains of influenza will emerge as pandemic threats; whether the company's DNA vaccine candidate will be effective in protecting humans against H5N1 or other strains of influenza; whether the measles vaccine will be effective in protecting juvenile or infant humans against infection or disease; whether the influenza or measles vaccines or any other product candidates will be shown to be safe and effective; the timing, nature and cost of clinical trials; whether Vical or its collaborative partners will seek or gain approval to market the influenza vaccine or any other product candidates; whether Vical or its collaborative partners will succeed in marketing the influenza vaccine or any other product candidates; and additional risks set forth in the company's filings with the Securities and Exchange Commission. These forward-looking statements represent the company's judgment as of the date of this release. The company disclaims, however, any intent or obligation to update these forward-looking statements.

Vical Incorporated
http://www.vical.com

[Preciouslife1]

Insights Into Cell Specificity Of Human Vs. Avian Viruses



Researchers have identified which sites and cell types within the respiratory tract are targeted by human versus avian influenza viruses, providing valuable insights into the pathogenesis of these divergent diseases. The report by van Riel et al, "Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals," appears in the October issue of The American Journal of Pathology and is accompanied by a commentary and highlighted on the cover.

Differences in cellular expression of target molecules correspond to host specificity of influenza viruses. They also define which organs or tissues are infected within the host. For example, highly pathogenic H5N1 avian influenza virus targets cells deep within the lower respiratory tract whereas human influenza virus is thought to target cells of the upper respiratory tract, including the trachea.

To better elucidate the differences between low and highly pathogenic avian influenza virus versus human influenza virus, researchers led by Dr. Thijs Kuiken of Erasmus MC, Rotterdam, The Netherlands, used a technique called virus histochemistry. This method examines the attachment pattern of influenza virus to isolated respiratory tissues, thus identifying the cells targeted by the virus.

When human viruses were tested, both attached strongly to the trachea and bronchi, but virus binding to the bronchioles and alveoli (deeper within the lung) was less abundant in comparison. In contrast, viral attachment of avian viruses was rare in the trachea but more abundant in the bronchioles and alveoli. Further, the cellular targets in the alveoli also differed: human virus preferred type I pneumocytes whereas avian virus bound type II pneumocytes and alveolar macrophages. Interestingly, low and highly pathogenic avian influenza viruses attached to the same cell types, demonstrating that factors other than binding ability must contribute to the pathogenicity.

These data are consistent with the differences in human disease presentation, with human influenza causing tracheobronchitis and highly pathogenic avian influenza causing severe pneumonia. But which animal models are the best for studying the disease in humans" To answer this question, the authors next assessed the pattern of virus attachment in animal models used for influenza studies. Of several mammals tested, ferrets, cats, and pigs most closely resembled the human patterns of virus attachment for avian influenza viruses, thus demonstrating their usefulness as models of infection and disease.

These studies "improve our understanding of the pathogenesis of human respiratory tract disease from both human and avian influenza A virus infection," state the authors. Combined with the results obtained with different animal models, they may lead to a better understanding of the factors that are critical for virus binding and infection, enabling the future development and testing of feasible control strategies.

[katebright]

I came across an article on bird flu. Just have a look.

http://www.caring.com/news/new-weapo...attle-bird-flu