Influenza and Pandemic Influenza: Are New Vaccines and Therapeuticals coming as current defense waning?

[Giuseppe]

Bird flu vaccine production still lags-study | Reuters

Bird flu vaccine production still lags-study

Tue Feb 24, 2009 10:02am EST
(recasts with quotes from WHO briefing)
By Stephanie Nebehay
GENEVA, Feb 24 (Reuters) -

Drug companies would need four years to meet global demand for bird flu vaccines if a pandemic broke out today, but new technology could significantly boost production by 2014, a study said on Tuesday.


Doses of vaccine tailored to the actual strain of pandemic influenza that emerges would not be available until four months after it is identified, it said.

Consulting firm Oliver Wyman gathered confidential data from drugmakers for the study which projected at least a doubling of production by 2014 mainly due to vaccines being made in cells in a lab dish instead of chicken eggs.

The study was carried out with the World Health Organisation (WHO) and International Federation of Pharmaceutical Manufacturers and Associations (IFPMA).

"The bottom line is that the capacity to make pandemic vaccines has tripled over the last two years ... this is mainly driven by improvements in production yields and also in dose-sparing technologies," Marie-Paule Kieny, director of the WHO initiative for vaccine research, told a news conference.

"We still don't have enough to cover the whole world in the early months of a pandemic, even though the situation has improved."

Currently, drug makers could make up to 2.5 billion doses of pandemic vaccines in one year, meaning it would take four years to meet global demand, the study said. In a best-case scenario, they could make 7.7 billion doses in 1.5 years.

RACE AGAINST THE CLOCK
Manufacturers hunting for the best vaccines to stop the deadly disease face a race against the clock if the H5N1 strain of influenza now circulating in birds mutates and starts spreading easily among humans, as many researchers fear.

At least 20 firms are working on pandemic vaccines, Kieny said. Western makers including Europe's biggest drugmaker GlaxoSmithKline (GSK.L), France's Sanofi-Aventis (SASY.PA), Switzerland's Novartis (NOVN.VX) and Baxter International (BAX.N) of the United States accounted for most of the expanded capacity.

Production capacity was expected to increase to 5.1-14.7 billion doses by 2014, taking 12-28 months to meet global demand, the study said.

"The big increase between now and 2014 is due to the coming on to the market of vaccines made on cell cultures," Kieny said. "But this is still a projection."

Even by 2014, not all countries would have access to pandemic vaccine in the first six to nine months after the pandemic erupted, she added. There was concern that "developing countries will have little or no vaccines at the beginning".

The WHO, a United Nations agency, was making available a total of $12 million in grants to 11 developing countries to help them develop vaccine manufacturing capacity, she said.

Current demand for seasonal influenza vaccine is about 500 million doses a year, whereas drug makers currently have the capacity to make about 800 million doses, Kieny said.

Bird flu has killed 255 people out of 408 infected worldwide since 2003, according to the WHO. The toll includes a 23-year-old woman in Vietnam who died on Saturday.

(Editing by Jonathan Lynn)
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<cite cite="http://www.reuters.com/article/latestCrisis/idUSLO565851">Bird flu vaccine production still lags-study | Reuters</cite>

 

[Giuseppe]

Re: Bird flu vaccine production still lags-study | Reuters

Re: Bird flu vaccine production still lags-study | Reuters

WHO to give poor countries flu vaccine technology

WHO to give poor countries flu vaccine technology

By FRANK JORDANS, Associated Press Writer
GENEVA ?

The World Health Organization said Tuesday that a deal with U.S. drug maker Schering-Plough Corp. will allow it to provide poor countries with improved vaccine-making technology to prepare for a possible flu pandemic.


WHO will license the technology free of charge to vaccine manufacturers in developing countries who take part in a U.N. action plan to stop a global outbreak of the deadly H5N1 flu strain.

Schering-Plough, based in Kenilworth, New Jersey, said in a statement that the new technology allows vaccines to be delivered more efficiently using a single-dose intranasal spray.

A recent study released by the pharmaceutical industry group IFPMA found that if an H5N1 pandemic outbreak occurred today, manufacturers would likely need four years to meet global demand for a vaccine.

Vaccine makers have increased their capacity threefold in the last two years thanks to improved production yields and new dose-saving technologies, the study found.

Even in a "best case scenario" where vaccines are produced in the most efficient possible way, it would currently take one-and-a-half years to meet global demand.

With efforts under way to ramp up global vaccine production capacity, the time it would take to make enough vaccines for everybody can be reduced to between one and two-and-half years by 2014, according to the study, which was funded by the Bill and Melinda Gates Foundation.

Marie-Paule Keany, the head of WHO's vaccine research initiative, welcomed the increased production rate, but noted that manufacturers were seeing a growing gap between capacity and demand.

Until a deadly pandemic occurs, drug makers are using their factories to produce seasonal influenza vaccines, which are recommended in many countries for elderly and weak people most at risk from common flu.

"To keep operating plants which are not producing anything is costly," Keany said. "If they close them down, they de facto also close down capacity to produce pandemic vaccine."
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<cite cite="http://news.yahoo.com/s/ap/20090224/ap_on_he_me/un_un_bird_flu_schering">WHO to give poor countries flu vaccine technology</cite>

 

[Giuseppe]

Re: Bird flu vaccine production still lags-study | Reuters

Re: Bird flu vaccine production still lags-study | Reuters

Authoritative New Study Reveals Global Pandemic Influenza Vaccine Capacity

Authoritative New Study Reveals Global Pandemic Influenza Vaccine Capacity

Article Date: 24 Feb 2009 - 6:00 PST

Vaccine manufacturers have substantially increased their capacity to produce pandemic influenza vaccines during the past two years, according to a new study by Oliver Wyman, an international strategy consulting firm.


Importantly, this study arrived at capacity estimate numbers that the global health community agrees upon, after considerable prior debate.

Conducted in collaboration with the World Health Organization (WHO) and The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA)1, the new study finds that while capacity is increasing, it would not be sufficient to meet the global need for emergency production of pandemic influenza vaccines at the time of a pandemic.

However, the study notes that current and future surplus capacity could support the production of billions of doses of H5N1 influenza vaccine prior to a pandemic for stockpiling efforts and other utilization.

"We found that considerable progress has been made to enhance the production capacity of pandemic influenza vaccine," said Adam Sabow, partner at Oliver Wyman who led the study. "While capacity still falls short of global need during a pandemic, the surplus capacity during the inter-pandemic period creates opportunities for preparedness efforts. For example, we are working with the WHO to design a global H5N1 vaccine stockpile. If demand does not exist to utilize this excess capacity, however, manufacturers are likely to rationalize some of it, creating further shortages at the time of a pandemic."

IFPMA Director General Alicia D. Greenidge said, "This study advances our understanding of the world's ability to address pandemic influenza, and demonstrates the progress made by our member companies in developing new vaccine technologies and expanding production facilities. Our member companies are committed to working with the WHO and countries to ensure that we make the best use of the surplus capacity to prepare for a pandemic. The findings suggest that the early use of stockpiled H5N1-based vaccines, followed by pandemic vaccines as soon as these become available, offers a realistic strategy to address this significant threat."

The new Oliver Wyman study provides a number of further insights:

- Pandemic influenza vaccine production capacity has increased by 300 percent over the last two years, largely driven by improvements in production yields and dosage-sparing technologies.

- With current technology, doses of vaccine tailored to the actual pandemic influenza strain will not be available until four months after identification of that strain by the WHO due to the technical lead time required to adapt the strain for vaccine production, manufacture vaccine, and distribute product.

- In the base (most likely) case2, manufacturers could produce 2.5 billion doses of pandemic vaccine in the 12 months following receipt of the production strain, requiring 4 years to satisfy global demand. In the best case, 7.7 billion doses could be produced in the first 12 months, requiring 1 ? years to satisfy global demand.

- This capacity is expected to rise to 5 - 14.5 billion doses over the next five years. The resulting time to meet global demand would be reduced to between 2? years (in the base case) and 1 year (in the best case).

- Surplus capacity (above current seasonal influenza and stockpile demand) currently exists to produce 2.5 billion annual doses of H5N1 vaccine prior to a pandemic. This surplus capacity is expected to rise to between 2.6 and 5.4 billion doses per year over the next 5 years.

Oliver Wyman initiated this study in 2008 in cooperation with the WHO and the IFPMA, with funding from the Bill & Melinda Gates Foundation.

1 Oliver Wyman also consulted with 11 other current or potential influenza vaccine manufacturers in developing countries which are not members of the IFPMA.
2 The "base" and "best" cases are based on different assumptions relating to a number of factors, including the level of demand for seasonal influenza and H5N1 vaccine in the inter-pandemic period, the yields that can be attained, the level of antigen-sparing achievable and the degree of rationalization of traditional egg-based vaccine production capacity as new cell-based capacity comes on line. In both cases, effective coverage is calculated based on 2 doses per person, for a global population of 6.7 billion.

About the IFPMA
The International Federation of Pharmaceutical Manufacturers & Associations is the global non-profit NGO representing the research-based pharmaceutical, biotech and vaccine sectors. Its members comprise leading international companies and national and regional industry associations covering developed and developing countries.
International Federation of Pharmaceutical Manufacturers & Associations
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<cite cite="http://www.medicalnewstoday.com/articles/140106.php">Authoritative New Study Reveals Global Pandemic Influenza Vaccine Capacity</cite>

 

[Giuseppe]

Re: Bird flu vaccine production still lags-study | Reuters

Re: Bird flu vaccine production still lags-study | Reuters

CIDRAP >> Pandemic vaccine?making capacity rising, but still short

Pandemic vaccine?making capacity rising, but still short

Robert Roos * News Editor
Feb 24, 2009 (CIDRAP News) ?

The world's capacity to produce vaccines for an influenza pandemic has risen sharply in the past 2 years, but it would still take an estimated 4 years to meet the global demand if a pandemic emerged now, according to a report from an international strategy consulting firm.


The report was prepared by the New York City?based firm Oliver Wyman in collaboration with the World Health Organization (WHO) and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA).

"Pandemic vaccine production capacity has increased by 300 percent over the last two years, largely driven by improvements in production yields and dosage-sparing technologies," Oliver Wyman stated in a news release. The company did not release the full report.

If a pandemic emerged this year, the most likely case is that manufacturers could produce 2.5 billion doses in the first 12 months after they received the production strain, the firm said. It would take 4 years to produce enough to meet total global demand, meaning two doses for each of the world's 6.7 billion people.

In the best case, the industry could produce 7.7 billion doses in the first 12 months of a pandemic and could meet global demand in 1? years, the firm said.

The company predicts that annual pandemic vaccine production capacity will rise to somewhere between 5 billion and 14.5 billion doses over the next 5 years. That means the time needed to meet global demand could drop to 2? years in the most likely case or 1 year in the best case.

The firm also expects that surplus vaccine production capacity?above and beyond the demand for seasonal flu vaccine and prepandemic vaccine stockpiling?will increase over the next 5 years, to between 2.6 billion and 5.4 billion annual doses. How much the capacity actually rises is likely to depend on the demand for both seasonal and prepandemic vaccines, officials said.

"I think this is a mixed story," Adam Sabow, the Wyman partner who led the preparation of the report, told CIDRAP News. "This is good if there's new seasonal [flu vaccine] demand or if there's demand for H5N1 vaccine during the interpandemic period for efforts such as stockpiling.

"However, if there isn't demand, there's a possibility that some of that capacity could be rationalized. By that we mean that capacity may either be shut down or may be redeployed for other purposes," which would reduce the ability to respond quickly to a pandemic.

He noted that there is some demand for H5N1 prepandemic vaccines, as some countries are stockpiling them, while the WHO is working on designing a global H5N1 vaccine stockpile. He said his firm is working with the WHO on that project.

Alicia D. Greenidge, director-general of the IFPMA, said member companies are committed to working with the WHO and governments to ensure the best use of surplus vaccine capacity to prepare for a pandemic. "The findings suggest that the use of stockpiled H5N1-based vaccines, followed by pandemic vaccine as soon as these become available, offers a realistic strategy to address this significant threat," she commented in the Wyman news release.

Agreement on numbers
Sabow said that to estimate vaccine production capacity, his firm included 44 existing and planned vaccine production facilities, representing "the vast majority" of such facilities.

He said the report marks a first: "This study is the first time that all the major actors have come together to agree on the capacity numbers for pandemic influenza. There's historically been a debate about the numbers that has taken away from the policy discussion. We're excited about this because the global health community has come together and agreed on the numbers and now can move on to the policy implications."

The report estimates that once a pandemic is recognized, it will take 4 months to develop, produce, and begin distributing a specific vaccine for it. Sabow said the estimate assumes the use of conventional egg-based production.

"We worked very closely with the WHO and the manufacturers to break down the individual parameters of that lead time, and a lot of work has been done to make that lead time as short as possible," he said. "This is currently the best information that our group has analyzed with regard to a realistic time at the point of a pandemic."

Egg-based and cell-based production
Although cell culture technology has been described as a faster and more flexible method for making flu vaccine, Sabow said the time needed to start making a pandemic vaccine would probably be about the same with cell culture production.

"We did model this for both egg-based and cell-based production, and the expectation is that cell-based production would have a relatively similar time frame," he said.

While most flu vaccine production remains egg-based, the amount of cell-based production capacity is expected to increase considerably in the next 5 years, Sabow noted.

One of the uncertainties is what will happen to egg-base production capacity as cell-based capacity comes on line, particularly if demand for seasonal and prepandemic vaccines is lacking. "If there isn't demand, some of that egg-based capacity may be rationalized," he said.

A chart released by Wyman gives more specific estimates of how much vaccine could be produced in the first few months of a pandemic. It indicates that once a pandemic is declared, it will take 3 to 4 weeks to create a reference strain for vaccine production.

In the most likely case, production would reach 340 million doses at 4 months after vaccine makers receive the reference strain, according to the chart. Production would reach 580 million doses at 5 months, 860 million doses at 6 months, and 2.45 billion doses at 12 months.

Possible constraints
Sabow said the Wyman analysis did not consider potential economic constraints on vaccine production and distribution or the possible effects of supply-chain disruptions, which many experts regard as likely during a pandemic.

"The intent of our work was to say, based on the production capabilities of those facilities, what do we think the overall production looks like at the point of a pandemic," he said. "We did not analyze what the financial implications would be or whether there would be funding for production or who would have access to it, and did not look at the possible supply-chain issues. That was not part of this analysis."

Sabow said the projections related to production of prepandemic vaccine stockpiling refer to H5N1 vaccines, but the estimates of production of actual pandemic vaccines do not assume that the next pandemic virus will be an H5N1 strain. "This is based on the history of producing a range of different influenza vaccine strains," he said.

See also:
IFPMA news release about Wyman report http://www.ifpma.org/pdf/2009_02_24_Release_IVS_Wyman_Capacity_24Feb09.pdf
IFPMA influenza site http://www.ifpma.org/influenza/
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<cite cite="http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/feb2409vaccine-jw.html">CIDRAP >> Pandemic vaccine?making capacity rising, but still short</cite>

 

[Giuseppe]

Second team finds natural super flu fighter - Reuters

Second team finds natural super flu fighter - Reuters

Second team finds natural super flu fighter - Reuters

Second team finds natural super flu fighter

Thu Feb 26, 2009 7:37pm GMT
WASHINGTON, Feb 26 (Reuters) -

An antibody being developed by a Dutch drug company chokes off both seasonal flu and the H5N1 avian flu virus and might offer a way to develop better treatments and vaccines, researchers reported on Thursday.


Crucell NV's (CRCL.AS) antibody, a naturally occurring immune system protein, grabs onto a hidden part of flu viruses, stopping them from infecting cells, they reported in the journal Science.

It is the second report in a week to find antibodies that can interfere with a range of strains of flu -- one of the hardest viruses to fight because it mutates so much.

"This is very exciting because it marks the first step toward the Holy Grail of influenza vaccinology -- the development of a durable and cross-protective universal influenza virus vaccine," Ian Wilson, a researcher at he Scripps Research Institute in La Jolla, California, who helped lead the research, said in a statement.

"Such a flu vaccine could be given to a person just once and act as a universal protectant for most subtypes of influenza, even against pandemic viruses."

On Sunday, another research team said they had found a batch of antibodies that do something similar.

Flu vaccines and drugs focus on proteins found on the surface of the flu virus called hemagglutinin and neuraminidase, which give influenza A viruses their names, as in H5N1 or H1N1.

Hemagglutinin is a lollipop-shaped structure with a big, round head. This head is so large that it attracts most of the immune system antibodies -- which then slip off when it mutates.

Because of the mutations, vaccines have to be reformulated every year and the viruses can develop resistance to antiviral drugs.

The antibodies found by Wilson's group and the U.S. team earlier this week attach to the "stick" of the hemagglutinin lollipop. This mutates less than the head, and so provides less of a moving target.

In both studies, the antibody suppressed a range of flu viruses, including H5N1 avian flu and the currently circulating H1N1 seasonal flu virus, although they did not work well against another seasonal flu virus called H3N2.

Wilson's team and Crucell Holland found their antibody, called CR6261, in the blood of people who had been vaccinated with the ordinary seasonal flu vaccine.

Similar antibodies have now also been found in other people, but it is not clear how well they protect people from flu or whether some people's bodies use them more efficiently than others.

Both groups said their antibodies provide a way to treat people infected with flu, as well as a route to designing better drugs and vaccines.

(Reporting by Maggie Fox; Additional reporting by Julie Steenhuysen in Chicago; Editing by Eric Walsh)
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<cite cite="http://uk.reuters.com/article/governmentFilingsNews/idUKN2641112820090226?sp=true">Second team finds natural super flu fighter | Deals | Regulatory News | Reuters</cite>

 

[Gert van der Hoek]

Re: Second team finds natural super flu fighter - Reuters

Re: Second team finds natural super flu fighter - Reuters


- snip -

The results of this study will be presented by Dr Robert Friesen, Crucell's Vice President Antibody Discovery, at the 8th Asia Pacific Congress of Medical Virology, on the 27th of February 2009 in Hong Kong.

http://cws.huginonline.com/C/132631/PR/200902/1293663_5_5.html

 

[Gert van der Hoek]

Re: Second team finds natural super flu fighter - Reuters

Re: Second team finds natural super flu fighter - Reuters

Presentation by Dr Robert Friesen at the Hong Kong Congress:

http://www.crucell.com/page/downloads/090227_APCMV_Struct.pdf

 

[Giuseppe]

Re: Second team finds natural super flu fighter - Reuters

Re: Second team finds natural super flu fighter - Reuters

New drugs needed to fight flu pandemic | Health | Reuters

New drugs needed to fight flu pandemic

Fri Feb 27, 2009 6:14am EST
By Tan Ee Lyn
HONG KONG (Reuters) -

Experts on Friday urged governments on Friday to diversify their stockpiles of drugs and called for more new medicines to fight what could be the world's next flu pandemic caused by the H5N1 bird flu virus.


Many advanced countries stock up on oseltamivir and zanamivir, two varieties of the same class of drugs that stops the H5N1 virus from multiplying.

But oseltamivir has proven to be largely useless in fighting the H1N1 seasonal human influenza virus and experts are questioning how well, and how long, the drug would stand up against the H5N1 virus, should it unleash a pandemic.

"We have been extremely foolish on our policies of stockpiling drugs. We have been stockpiling two varieties of the same drug," virologist Robert Webster at the St Jude Children's Hospital in the United States said at a medical conference in Hong Kong.

He said the resistance of the H1N1 virus to oseltamivir was as high as 98 percent worldwide.

"The likely scenario is that the (H5N1) virus will become resistant when you start using more and more (of one) drug, you get resistant (H5N1) mutants," he told Reuters later.

The U.S. Centers for Disease Control and Prevention said in December 2008 that 49 out of 50 H1N1 virus samples tested were no longer sensitive to oseltamivir, which is made by Roche AG and Gilead Sciences Inc..

Relenza, known generically as zanamivir, is made by GlaxoSmithKline under license from Australia's Biota Inc..

Viruses and bacteria are sturdy organisms that fight hard to survive and adapt swiftly to drugs that are used to kill them, quickly becoming resistant to them.

Experts at the conference said most H1N1 viruses were sensitive to oseltamivir just a few years ago but learnt to adapt to the drug very quickly.

They warned that H5N1 could learn to adapt quickly to oseltamivir, just as H1N1 has done, because both viruses share a similar "N1" protein component.

Scientists in Vietnam reported in the past how certain strains of H5N1 were no longer sensitive to oseltamivir, resulting in the deaths of several infected patients.

Experience with viruses similar to H5N1 suggests that it would best be tackled with a combination of drugs, Webster said.

"Studies with HIV, leukemia have shown that we have to use multiple drugs," he said. He suggested that oseltamivir and zanamivir be trialled alongside other drugs like ribavirin and the adamantane class of drugs, like amantadine and rimantadine.

Malik Peiris a microbiologist with the University of Hong Kong said: "There is a need for developing new antivirals (drugs). Some are in very early clinical trials but development should be stepped up so there is a diversification of options."

(Editing by Valerie Lee)
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<cite cite="http://www.reuters.com/article/healthNews/idUSTRE51Q1VI20090227">New drugs needed to fight flu pandemic | Health | Reuters</cite>

 

[Giuseppe]

Re: Second team finds natural super flu fighter - Reuters

Re: Second team finds natural super flu fighter - Reuters

CIDRAP >> Another antibody against diverse flu strains found

Another antibody against diverse flu strains found

Robert Roos * News Editor
Feb 27, 2009 (CIDRAP News) ?

For the second time this week, scientists have reported the discovery of a human antibody that, at least in theory, could lead to development of a vaccine or drug effective against most types of influenza A, including the deadly H5N1 avian flu virus.


A team from the Scripps Research Institute in La Jolla, Calif., and the Dutch company Crucell Holland BV describe the new antibody, called CR6261, in a report in Science. They write that the antibody recognizes a stable, or nonmutating, region of the hemagglutinin (HA) protein in the 1918 pandemic flu virus and a 2004 strain of the H5N1 virus.

As it is described, the antibody targets the same general region of the HA protein as do the monoclonal antibodies described in the report published Feb 22: the stem or neck of the molecule, which sits on the surface of the virus and helps it bind to host cells. And like the earlier report, the new one says the antibody neutralizes the virus by blocking it from fusing with cells.

"The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion," the Science report states. "Identification of the CR6261 epitope [the HA site the antibody targets] provides a lead for the design of antivirals and takes a significant step towards the development of a durable and cross-protective 'universal' vaccine against influenza A," it concludes.

The National Institute of Allergy and Infectious Diseases, which provided funding for both studies released this week, said in a statement yesterday, "Taken together, these studies provide a blueprint for efforts to develop new antiviral drugs as well as a potential universal flu vaccine."

The scientists, with Damian C. Ekiert of Scripps as first author, write that they isolated CR6261 from a healthy, vaccinated person by mixing a serum sample with HA from an H5 virus. In a previously reported study, they found that CR6261 neutralized several influenza A subtypes, including H1, H2, H5, H6, H8, and H9. They also found that it protected mice from H1N1 and H5N1 viruses when administered up to 5 days after infection.

To determine which part of the HA molecule the antibody targets and how it neutralizes the virus, the team studied the crystal structures of the antibody in combination with HAs from the 1918 H1N1 virus and a 2004 Vietnam strain of the H5N1 virus. They found that the antibody attaches to the base of the proteins rather than to the mushroom-shaped head?the portion targeted by existing flu vaccines.

In further experiments, the scientists concluded that the antibody prevents HA from initiating the process of fusing the viral membrane with the host cell membrane. "CR6261 appears to neutralize the virus by stabilizing the pre-fusion state and preventing the pH-dependent fusion of viral and cellular membranes," the report says.

The researchers also analyzed more than 5,000 HA genetic sequences in a flu database in an effort to learn why certain flu subtypes, such as H3 and H7, are not neutralized by CR6261. They concluded that the masking of a certain site on the HA molecule by glycoproteins (glycosylation) is the probable reason. From this analysis, they concluded that the antibody probably can neutralize HAs from 12 of the 16 influenza A subtypes: H1, H2, H4-H6, H8, H9, H11-H14, and H16.

The presence of the CR6261 epitope in a wide range of influenza viruses "suggests a critical role in membrane fusion," indicating the possibility of using it to develop new antiviral drugs and a broadly protective vaccine, the researchers write.

Experts who were not involved in the study said the latest findings are very similar to those reported earlier this week in Nature Structural and Molecular Biology.

John Treanor, MD, a vaccine researcher and professor of microbiology and immunology at the University of Rochester in New York, called the idea of using the "fusion region" of HA to develop a vaccine interesting, though not entirely new. "It's a long way to go between knowing you have an antibody that can recognize that region and making a vaccine," he said.

If the CR6261 target region were used to make a vaccine designed to induce the immune system to generate similar antibodies, immunogenicity could be a challenge, Treanor said. "Bear in mind that you don't really make this antibody when you're exposed [to flu viruses], or you don't make much of it. So presumably you'd have to cook up some way of presenting the epitope in such a way as to make it immunogenic."

He said the findings certainly raise the possibility making CR6261 antibodies for use as a flu treatment. "I don't have any doubt that we could do that. I will say that if the experience with palivizumab is any guide, you'd expect this type of passive antibody approach to be much more effective for prevention than for treatment."

Palivizumab is a human monoclonal antibody used to protect certain vulnerable children from serious infections with respiratory syncytial virus, he said.

Dr. Richard Webby, a virologist, flu researcher, and associate member of the Department of Infectious Diseases at St. Jude Children's Research Hospital in Memphis, called the latest findings "great stuff."

Given that monoclonal antibodies are already used to treat certain diseases, the findings certainly point to a possibility of antibody-based therapies for flu, he said.

"There are some limitations on the wider use of this approach, cost being the major one," he said. "As production techniques improve and costs come down, it becomes a little bit more viable."

Webby added that antibody-based flu therapies have been "very, very effective" in animal models, surpassing other drugs. "So I absolutely think it's an avenue that needs to be pursued aggressively."

As for the vaccine possibilities, he noted that a number of researchers are trying to make vaccines that induce immunity to more stable parts of influenza viruses, including sites on the HA, and have had mixed success. "There's no doubt that if we want to produce a more cross-reactive vaccine against influenza, we have to understand more about these cross-reactive epitopes," he said.

Ekiert DC, Bhabba G, Elsliger, MA, et al. Antibody recognition of a highly conserved influenza virus epitope. Science 2009 Feb 26 (early online publication) [Abstract]

See also:
Feb 26 NIAID statementhttp://www3.niaid.nih.gov/news/newsreleases/2009/flu_universal.htm
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<cite cite="http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/feb2709antibody.html">CIDRAP >> Another antibody against diverse flu strains found</cite>

 

[Giuseppe]

Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

[The abstract of the paper about this vaccinia virus-based H5N1 vaccine is available at: http://www.flutrackers.com/forum/showthread.php?t=95621 - IOH]

Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Experts fight H5N1 bird flu using smallpox vaccine

01 Mar 2009 08:02:47 GMT
Source: Reuters
By Tan Ee Lyn
HONG KONG, March 1 (Reuters) -

Scientists in Hong Kong and the United States have developed an experimental H5N1 bird flu vaccine for people by piggybacking it on the well-tested and highly successful smallpox vaccine.


Initial tests on mice showed the vaccine to be highly effective, they told a news conference in Hong Kong on Sunday.

"It produced a lot of (H5N1) antibodies and the speed of antibody response was far higher with this strategy than the Sanofi one," said Malik Peiris, a microbiologist and bird flu expert at the University of Hong Kong.

Peiris was referring to Sanofi-Aventis's <sasy.pa> H5N1 bird flu vaccine for humans, which has been approved for use in the United States.

In an article published in the current Journal of Immunology, the experts from Hong Kong and the U.S. National Institutes of Health described how they inserted five key components of the H5N1 virus into the smallpox vaccine.

"We put in many other proteins into that vaccine; we are using it like a carrier, if you like, a piggyback," Peiris said.

The vaccine uses a Vietnam strain of the H5N1 virus and appeared to be broadly protective. Mice which were inoculated with it successfully fought off an Indonesian strain of H5N1, according to the scientists.

Since 2003, the H5N1 avian influenza virus has infected 408 people in 15 countries and killed 254 of them. It has killed or forced the culling of more than 300 million birds as it spread to 61 countries in Asia, the Middle East, Europe and Africa.

While H5N1 rarely infects people, experts fear it could mutate into a form that people could easily pass to one another, sparking a pandemic that could kill tens of millions and topple the global economy.

Smallpox was eradicated worldwide in 1979 and the experts are hoping that their novel H5N1 vaccine can ride on the various advantages of the smallpox vaccine.

The smallpox vaccine is very cheap, has a long shelf-life of several years and does not require highly sophisticated laboratories, making it easier for poorer countries to produce.

"It is very stable and you can pack them off to developing countries and use them. They require refrigeration but it is less critical than other vaccines," Peiris said.

"Smallpox production capacity has gone down but many countries have the technology and the expertise to do it, and if necessary, it can be very quickly scaled up."

"But for other strategies (of producing H5N1 vaccines), it is not possible to rapidly set up manufacturing plants all over the world as they require very specialised plants."

However, it will take at least a few more years before the vaccine would be ready for the market. It must be tested next in ferrets, then monkeys, before human clinical trials can be carried out.

(Editing by Kim Coghill)
-
</sasy.pa>​

<cite cite="http://www.alertnet.org/thenews/newsdesk/HKG196430.htm">Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine</cite>

 

[sharon sanders]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

"..The vaccine uses a Vietnam strain of the H5N1 virus and appeared to be broadly protective. Mice which were inoculated with it successfully fought off an Indonesian strain of H5N1, according to the scientists..."

snip


"..However, it will take at least a few more years before the vaccine would be ready for the market. It must be tested next in ferrets, then monkeys, before human clinical trials can be carried out..."

 

[SophiaZoe]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Concern over the use of the Smallpox vaccine as a "delivery system" are raised because the Smallpox vaccine is only recommended for immonocompetent recipients. The researchers inclusion of the IL-15 cytokine circumvents this according to the paper:

All of these attributes of IL-15 favoredour selection of this cytokine as an immune-enhancing molecularadjuvant in our vaccines against H5N1 Ags that are known tobe poorly immunogenic. Equally important is the observationthat the Dryvax vaccine, which can cause severe vaccinal diseasein immunodeficient hosts, loses its virulence markedly withthe incorporation of IL-15 as we have shown previously.Thus, our selection of IL-15 to be integrated into our DryvaxWyeth strain-based pentavalent H5N1 vaccine facilitated achievingboth immune enhancement as well as attenuation of the virulenceof these vaccines.

However, what concerns me more is the use of 5 genetic components of H5 in one iteration of the experiment:

With this objective, we generatedvaccinia virus-based vaccine candidates that tandemly expresseither five genes of H5N1 influenza A virus, namely the H5 hemagglutiningene, the N1 neuraminidase gene, the nucleoprotein NP gene,and genes encoding the two matrix polypeptides M1 and M2 alongwith the cytokine IL-15 on the backbone of the Wyeth strainof vaccinia, or only the two surface genes, H5 hemagglutininand N1 neuraminidase, with IL-15 on the modified vaccinia virusAnkara (MVA) backbone.

Of course, I am not a scientist, nor an expert, so perhaps my "concern" is simply more "knee jerk" than valid.

 

[sharon sanders]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Concern over the use of the Smallpox vaccine as a "delivery system" are raised because the Smallpox vaccine is only recommended for immonocompetent recipients. The researchers inclusion of the IL-15 cytokine circumvents this according to the paper:



However, what concerns me more is the use of 5 genetic components of H5 in one iteration of the experiment:



Of course, I am not a scientist, nor an expert, so perhaps my "concern" is simply more "knee jerk" than valid.

I agree. I am generally concerned about using the Smallpox vaccine as a delivery vehicle for H5N1. :magnify:

 

[AlaskaDenise]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

What are other examples of "piggybacked" vaccines?

Are there examples of nature utilizing a similar technique for either new pathogens or as part of the defense process?

As a non-scientist, it appears they're created new "hybrid" pathogen. Is that true?

The paper indicated their desire to piggyback other vaccines onto the smallpox vaccine. Can they assume they would all have the same reaction?

How can testing be 100% conclusive that this technique is free of unintended consequences?

.

 

[mixin]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

A quick search brought this up:

Piggyback Vaccines
Another area of potential significance involves the use of genetic engineering to produce subunit vaccines against viruses such as those that cause herpes and hepatitis. Genes encoding part of the protein-polysaccharide coat of the herpes simplex virus or hepatitis B virus are spliced into a fragment of the vaccinia (cowpox) virus genome (figure 18). The vaccinia virus, which British physician Edward Jenner used almost 200 years ago in his pioneering vaccinations against smallpox, is now used as a vector to carry the herpes or hepatitis viral coat gene into cultured mammalian cells.

These cells produce many copies of the recombinant virus, which has the outside coat of a herpes or hepatitis virus. When this recombinant virus is injected into a mouse or rabbit, the immune system of the infected animal produces antibodies directed against the coat of the recombinant virus. It therefore develops an immunity to herpes or hepatitis virus. Vaccines produced in this way are harmless because the vaccinia virus is benign and only a small fragment of the DNA from the disease-causing virus is introduced via the recombinant virus.

The great attraction of this approach is that it does not depend upon the nature of the viral disease. In the future, similar recombinant viruses may be injected into humans to confer resistance to a wide variety of viral diseases.

In 1995, the first clinical trials began of a novel new kind of DNA vaccine, one that depends not on antibodies but rather on the second arm of the body's immune defense, the so-called cellular immune response, in which blood cells known as killer T cells attack infected cells. The infected cells are attacked and destroyed when they stick fragments of foreign proteins onto their outer surfaces that the T cells detect (the discovery by Peter Doherty and Rolf Zinkernagel that infected cells do so led to their receiving the Nobel Prize in medicine in 1996). The first DNA vaccines spliced an influenza virus gene encoding an internal nucleoprotein into a plasmid, which was then injected into mice. The mice developed strong cellular immune responses to influenza. New and controversial, the approach offers great promise.

Genetic engineering has produced commercially valuable proteins, gene therapies, and, possibly, new and powerful vaccines.

http://www.txtwriter.com/backgrounders/Genetech/GEpage18.html

 

[AlaskaDenise]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

A quick search ...

I was searching using various scientific terms, no wonder I missed it.

Another example from the poultry industry, but also only under development....

The IAH researchers want to discover what it is about the Eimeria parasite that causes chickens to develop a protective immune response. They are also looking at a technology known as ?transfection,? which enables pieces of DNA to be moved from one parasite into another. The technology might make it possible to develop a ?piggyback? vaccine with one parasite that would protect against all species of Eimeria.

.

 

[AlaskaDenise]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Transfection

From Wikipedia, the free encyclopedia

Transfection is the process of introducing nucleic acids into cells by non-viral methods [1]. The term transformation is preferred to describe non-viral DNA transfer in bacteria and non-animal eukaryotic cells such as fungi, algae and plants.

Transfection of animal cells typically involves opening transient pores or 'holes' in the cell plasma membrane, to allow the uptake of material. Genetic material (such as supercoiled plasmid DNA or siRNA constructs), or even proteins such as antibodies, may be transfected. In addition to electroporation, transfection can be carried out using calcium phosphate, or by mixing a cationic lipid with the material to produce liposomes, which fuse with the cell plasma membrane and deposit their cargo inside.

Terminology
The meaning of the term has evolved.[2]

The original meaning of transfection was 'infection by transformation', i.e. introduction of DNA (or RNA) from an eukaryote virus or bacteriophage into cells, resulting in an infection. Because the term transformation had another sense in animal cell biology (a genetic change allowing long-term propagation in culture, or acquisition of properties typical of cancer cells), the term transfection acquired, for animal cells, its present meaning of a change in cell properties caused by introduction of DNA.Transfection can result in unexpected morphologies and abnormalities in target cells.


Methods
There are various methods of introducing foreign DNA into a eukaryotic cell. Many materials have been used as carriers for transfection, which can be divided into three kinds: (cationic) polymers, liposomes and nanoparticles.

One of the cheapest (and least reliable) methods is transfection by calcium phosphate, originally discovered by F. L. Graham and A. J. van der Eb in 1973[3] (see also [4]). HEPES-buffered saline solution (HeBS) containing phosphate ions is combined with a calcium chloride solution containing the DNA to be transfected. When the two are combined, a fine precipitate of the positively charged calcium and the negatively charged phosphate will form, binding the DNA to be transfected on its surface. The suspension of the precipitate is then added to the cells to be transfected (usually a cell culture grown in a monolayer). By a process not entirely understood, the cells take up some of the precipitate, and with it, the DNA.

Other methods use highly branched organic compounds, so-called dendrimers, to bind the DNA and get it into the cell. A very efficient method is the inclusion of the DNA to be transfected in liposomes, i.e. small, membrane-bounded bodies that are in some ways similar to the structure of a cell and can actually fuse with the cell membrane, releasing the DNA into the cell. For eukaryotic cells, lipid-cation based transfection is more typically used, because the cells are more sensitive.

Another method is the use of cationic polymers such as DEAE-dextran or polyethylenimine. The negatively charged DNA binds to the polycation and the complex is taken up by the cell via endocytosis.

A direct approach to transfection is the gene gun, where the DNA is coupled to a nanoparticle of an inert solid (commonly gold) which is then "shot" directly into the target cell's nucleus. DNA can also be introduced into cells using viruses as a carrier. In such cases, the technique is called viral transduction, and, the cells are said to be transduced.

Other methods of transfection include nucleofection, electroporation, sonoporation, heat shock, magnetofection and proprietary transfection reagents such as Lipofectamine,Dojindo, GenePORTER, Hilymax, Fugene, jetPEI, Effectene or DreamFect.


Stable and transient transfection
For most applications of transfection, it is sufficient if the transfected gene is only transiently expressed. Since the DNA introduced in the transfection process is usually not inserted into the nuclear genome, the foreign DNA is lost at the later stage when the cells undergo mitosis.

If it is desired that the transfected gene actually remains in the genome of the cell and its daughter cells, a stable transfection must occur. To accomplish this, another gene is co-transfected, which gives the cell some selection advantage, such as resistance towards a certain toxin. Some (very few) of the transfected cells will, by chance, have inserted the foreign genetic material into their genome. If the toxin, towards which the co-transfected gene offers resistance, is then added to the cell culture, only those few cells with the foreign genes inserted into their genome will be able to proliferate, while other cells will die. After applying this selection pressure for some time, only the cells with a stable transfection remain and can be cultivated further.

A common agent for stable transfection is Geneticin, also known as G418, which is a toxin that can be neutralized by the product of the neomycin resistant gene.


See also
Protofection
Transformation
Transduction
Cationic liposome
Nucleofection

References
1.^ http://www.promega.com/guides/transfxn_guide/transfxn.pdf
2.^ Transfection at Dorland's Medical Dictionary
3.^ Graham FL, van der Eb AJ (1973). "A new technique for the assay of infectivity of human adenovirus 5 DNA". Virology 52 (2): 456?67. doi:10.1016/0042-6822(73)90341-3. PMID 4705382.
4.^ Bacchetti S, Graham F (1977). "Transfer of the gene for thymidine kinase to thymidine kinase-deficient human cells by purified herpes simplex viral DNA". Proc Natl Acad Sci U S A 74 (4): 1590?4. doi:10.1073/pnas.74.4.1590. PMID 193108.

External links
MeSH Transfection
Transfection at eMedicine Dictionary
Overview of transfection methods in Nature Methods 2, 875 - 883 (2005)

http://en.wikipedia.org/wiki/Transfection

 

[Sally Furniss]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

CDC
SMALLPOX FACT SHEET
Side Effects of Smallpox Vaccination

The smallpox vaccine prevents smallpox. For most people, it is safe and effective. Most people experience normal, typically mild reactions to the vaccine, which indicate that it is beginning to work. Some people may experience reactions that may require medical attention.
Normal, Typically Mild Reactions

These reactions usually go away without treatment:

• The arm receiving the vaccination may be sore and red where the vaccine was given.
• The glands in the armpits may become large and sore.
• The vaccinated person may run a low fever.
• One out of 3 people may feel bad enough to miss work, school, or recreational activity or have trouble sleeping.

Serious Reactions

In the past, about 1,000 people for every 1 million people vaccinated for the first time experienced reactions that, while not life-threatening, were serious. These reactions may require medical attention:

• A vaccinia rash or outbreak of sores limited to one area. This is an accidental spreading of the vaccinia virus caused by touching the vaccination site and then touching another part of the body or another person. It usually occurs on the genitals or face, including the eyes, where it can damage sight or lead to blindness. Washing hands with soap and water after touching the vaccine site will help prevent this (inadvertent inoculation).
• A widespread vaccinia rash. The virus spreads from the vaccination site through the blood. Sores break out on parts of the body away from the vaccination site (generalized vaccinia).
• A toxic or allergic rash in response to the vaccine that can take various forms (erythema multiforme).

Life-Threatening Reactions

Rarely, people have had very bad reactions to the vaccine. In the past, between 14 and 52 people per 1 million people vaccinated for the first time experienced potentially life-threatening reactions. These reactions require immediate medical attention:

• Eczema vaccinatum. Serious skin rashes caused by widespread infection of the skin in people with skin conditions such as eczema or atopic dermatitis.
• Progressive vaccinia (or vaccinia necrosum). Ongoing infection of skin with tissue destruction frequently leading to death.
• Postvaccinal encephalitis. Inflammation of the brain.

People with certain medical conditions?including people with weakened immune systems or certain skin conditions?are more likely to have these reactions and should not get the smallpox vaccine unless they have been exposed to smallpox.
Based on past experience, it is estimated that between 1 and 2 people out of every 1 million people vaccinated may die as a result of life-threatening reactions to the vaccine.
A Note on Recent Developments

Data from recent smallpox vaccinations have been found to be consistent with a causal association between vaccination and myopericarditis, although this is not proven. Persons receiving smallpox vaccine should be aware that myopericarditis is a potential complication of smallpox vaccination. If vaccinees experience chest pain, shortness of breath, or other symptoms of cardiac disease after vaccination they should seek medical attention. In addition, heart pain (angina) and heart attack also have been reported following smallpox vaccination, however, it is not known if smallpox vaccination caused these problems or if they occurred by chance alone.

A Note on Numbers: Most of the statistical information about smallpox vaccine adverse reactions cited in this fact sheet is based on data from two studies conducted in 1968. Adverse event rates in the United States today may be higher because there may be more people at risk from immune suppression (from cancer, cancer therapy, organ transplants, and illnesses such as HIV/AIDS) and eczema or atopic dermatitis. The outcome associated with adverse events may be less severe than previously reported because of advances in medical care. Rates may be lower for persons previously vaccinated.



http://www.bt.cdc.gov/agent/smallpox/vaccination/reactions-vacc-public.asp

 

[tropical]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

As quoted in the Sally #9 post, it is visible how tricky is to be vaccinated with the old kind of vaccine ('68 data).
The new ones would insert new dangers probably.

The sp vaccine in 2 world official depots was on a brink to be destructed because of twarthing any potential dangerous events (FT have a thread about when the WHO make the last decision about), but it remains.

Refreshing the memories with the book "The monster in the freezer".

This proliferation of new kinds of vacc/... which hav such an dangerous one as a base, mist with the new gentec of "transfections":
in this thread, #...: "Transfection can result in unexpected morphologies and abnormalities in target cells.",

"In the future, similar recombinant viruses may be injected into humans to confer resistance to a wide variety of viral diseases."

and the word "might", instead of "it can", means many freaky experimenting with doubtfull results, and much more dangers, of the type as seen recently with the seasonl-bf mixing episode.

#1:
""We put in many other proteins into that vaccine; we are using it like a carrier, if you like, a piggyback," Peiris said."

"Transfectioning" parts of who-knows-which organism genetic sequences after injected to sane organisms, knowing that such infections results in "unespected morphologies and abnormalities" would result in many new illnesses.

A source of permanent proliferation of microbial species variations.

A bunch of dangerous viruses on the wings of other dangerous viruses/... unleashed in labs/... worldwide probably isn't "the best" innovative idea of illness shieldings ...

Another dangerous global scientific experiment.

 

[Sally Furniss]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

from FDA site

FDA Approves Second-Generation Smallpox Vaccine

.... "This vaccine is manufactured using modern cell culture technology allowing rapid and large scale production of a vaccine with consistent product quality." ....... ACAM2000 is made using a pox virus called vaccinia, which is related to but different from the virus that causes smallpox. The vaccine contains live vaccinia virus and works by causing a mild infection that stimulates an immune response that effectively protects against smallpox without actually causing the disease. The vaccine is derived from the only other smallpox vaccine licensed by FDA, Dryvax, approved in 1931........
http://www.fda.gov/bbs/topics/NEWS/2007/NEW01693.html