New vaccine may beat bird flu before it starts

[Gert van der Hoek]

New vaccine may beat bird flu before it starts

09 Aug 2007

By Maggie Fox, Health and Science Editor

WASHINGTON, Aug 9 (Reuters) - Researchers studying bird flu viruses said on Thursday they may have come up with a way to vaccinate people ahead of a feared influenza pandemic.

Experts have long said there is no way to vaccinate people against a new strain of influenza until that strain evolves. That could mean months or even years of disease and death before a vaccination campaign began.

But a team at the National Institute of Allergy and Infectious Diseases in Maryland and the Emory University School of Medicine in Atlanta said they may have found a short-cut.

The vaccine might protect people against the mutation that would change the H5N1 avian flu virus from a germ affecting mostly birds to one that infects people easily, the NIAID's Dr. Gary Nabel and colleagues report in Friday's issue of the journal Science.

"What Dr. Nabel and his colleagues have discovered will help to prepare for a future threat," NIH Director Dr. Elias Zerhouni said in a statement.

"While nobody knows if and when H5N1 will jump from birds to humans, they have come up with a way to anticipate how that jump might occur and ways to respond to it."

H5N1 remains mainly a virus of birds, but experts fear it could mutate into a form easily transmitted from person to person and sweep the world. It has occasionally infected people, killing 192 people out of 319 known cases since 2003, according to the World Health Organization.

To better try and understand the threat, researchers have studied various strains of H5N1 and compared them to the worst known flu virus ever -- the H1N1 virus that killed anywhere between 50 million and 100 million people in 1918 and 1919.

They found a tiny mutation that makes one strain of the H1N1 virus more easily infect birds, and another one prefer humans. It lies in the part of the virus that attaches to cells in the respiratory tract.

They then made the same alteration in an H5N1 virus, and vaccinated mice with some of this genetically engineered H5N1 DNA.

They found one immune system protein called an antibody that could neutralize both types of H5N1 -- H5N1 adapted to birds, and an engineered form that would in thery prefer humans.

If a vaccine could be designed to protect people against viruses with this mutation, it might be used to vaccinate populations before a pandemic even started, the researchers said.

"Now we can begin, preemptively, to consider the design of potential new vaccines and therapeutic antibodies to treat people who may some day be infected with future emerging avian influenza virus mutants," NIAID director Dr. Anthony Fauci said in a statement. "This research could possibly help to contain a pandemic early on."

Companies are already making human vaccines against H5N1, but they are designed using the current strain of the virus, which does not easily infect people. Scientists fear they are a poor match for any form of the virus that may eventually infect people.

http://www.alertnet.org/thenews/newsdesk/N09237484.htm

[Gert van der Hoek]

Re: New vaccine may beat bird flu before it starts

NIH Scientists Target Future Pandemic Strains of H5N1 Avian Influenza


Preparing vaccines and therapeutics that target a future mutant strain of H5N1 influenza virus sounds like science fiction, but it may be possible, according to a team of scientists at the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health (NIH), and a collaborator at Emory University School of Medicine. Success hinges on anticipating and predicting the crucial mutations that would help the virus spread easily from person to person.

Led by Gary Nabel, M.D., Ph.D., director of the NIAID?s Dale and Betty Bumpers Vaccine Research Center (VRC), the team is reporting in the August 10, 2007 issue of the journal Science that they have developed a strategy to generate vaccines and therapeutic antibodies that could target predicted H5N1 mutants before these viruses evolve naturally. This advance was made possible by creating mutations in the region of the H5N1 hemagglutinin (HA) protein that directs the virus to bird or human cells and eliciting antibodies to it.

?What Dr. Nabel and his colleagues have discovered will help to prepare for a future threat,? says NIH Director Elias A. Zerhouni, M.D. ?While nobody knows if and when H5N1 will jump from birds to humans, they have come up with a way to anticipate how that jump might occur and ways to respond to it.?

?Now we can begin, preemptively, to consider the design of potential new vaccines and therapeutic antibodies to treat people who may someday be infected with future emerging avian influenza virus mutants,? says NIAID Director Anthony S. Fauci, M.D. ?This research could possibly help to contain a pandemic early on.?

Making a vaccine against an existing strain of H5N1 or any other type of influenza virus is relatively routine. Typically, samples of existing influenza virus strains are isolated and then grown inside eggs or in cell cultures. The virus is then collected, inactivated, purified and added to the other components of the vaccine.

A flu shot prompts a person?s immune system to detect pieces of the inactivated virus present in the vaccine and make neutralizing antibodies against them. Later, if that same person is naturally exposed to a flu virus, these same antibodies should help fight the infection.

Influenza viruses constantly mutate, however, and vaccines are most effective against the highly specific strains that they are made from. This makes it difficult to predict how effective a vaccine made today will be against a virus that emerges tomorrow.

Dr. Nabel and his colleagues started their project by focusing narrowly on mutations that render H5N1 viruses better able to recognize and enter human cells. Bird-adapted H5N1 binds bird cell surface receptors. But these receptors differ slightly from the receptors on human cells, which in part explains why bird-adapted H5N1 can infect but not spread easily between humans.

About a year ago, the research team began asking what mutations help the virus shift its adaptability. They compared the structural proteins on the surface of bird-adapted H5N1 influenza virus with those on the surface of the human-adapted strain that caused the 1918 pandemic. They focused specifically on genetic changes to one portion of the H5 protein ? a portion called the receptor binding domain. They showed that as few as two mutations to this receptor binding domain could enhance the ability of H5N1 to recognize human cells.

Additional mutations would likely need to accumulate for H5N1 to spread more easily from person to person, says Dr. Nabel. The few mutations he and his colleagues identified are likely just a subset of those, he emphasizes.

Moreover, they found that these mutations change how the immune system recognizes the virus. Mouse antibodies that target H5N1 were up to tenfold less potent against the mutants. Dr. Nabel and his colleagues used their knowledge of receptor specificity to create vaccines and isolate new antibodies that might be used therapeutically against human-adapted mutants.

They vaccinated mice with the material from viruses they altered to contain the mutant receptors, and they discovered one broadly reactive antibody that could neutralize both the bird- and human-adapted forms of an H5N1 virus.

According to Dr. Nabel, their findings should contribute to better surveillance of naturally occurring avian flu outbreaks by making it easier to recognize dangerous mutants and identify vaccine candidates that might provide greater efficacy against such a virus before it emerges.

?Our findings build on elegant studies of the influenza HA protein by structural biologists,? notes Dr. Nabel. ?Insight into the structure of the avian flu virus has enabled us to target a critical region of HA that directs its specificity. Such a structure-based vaccine design may allow us to respond to this future threat in advance of an actual outbreak.?

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH) ? The Nation's Medical Research Agency ? includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference: Z Yang et al. Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity. Science DOI: 10.1126/science.1135165 (2007).

Visit www.PandemicFlu.gov for one-stop access to U.S. Government information on avian and pandemic flu.

http://www.nih.gov/news/pr/aug2007/niaid-09.htm

[gsgs]

Re: New vaccine may beat bird flu before it starts

what's new here ?
I remember they did tests in Mice last year and determined that
a vaccine with S227N in the Vietnem-2003 virus was more
effective. Yet, I think Glaxo's vaccine hasn't that mutation.
I never understood, why.

[AlaskaDenise]

Re: New vaccine may beat bird flu before it starts

Researchers create H5N1 mutations to pave way for new vaccines and treatments

Aug 10, 2007 (CIDRAP News) ? Global health officials have long feared genetic changes that would make the H5N1 avian influenza virus more easily transmissible among humans, but a new report from researchers at the National Institute of Allergy and Infectious Diseases (NIAID) predicts some of the crucial mutations, which could open the door to preemptive vaccines and treatments.

The report, published in today's issue of Science, details the work of a research group led by Gary Nabel, MD, PhD, director of NIAID's Dale and Betty Bumpers Vaccine Research Center. The group created mutations in the region of the H5N1 hemagglutinin protein that directs the virus to bird or human receptor cells and elicits antibodies to it, according to a NIAID press release yesterday.

"What Dr Nabel and his colleagues have discovered will help prepare for a future threat," said National Institutes of Health director Elias A. Zerhouni, MD, in the press release. "While nobody knows if and when H5N1 will jump from birds to humans, they have come up with a way to anticipate how that jump might occur and ways to respond to it."

Typically, producing a vaccine to protect against H5N1 or another influenza virus strain is a laborious process that can take up to 6 months after a pandemic strain emerges. Scientists must isolate the strain, grow it in eggs or cell culture, and combine the purified virus with other vaccine components.

However, Anthony Fauci, MD, director if NIAID, said in the press release that researchers' findings on the artificially mutated viruses enable scientists to start considering the design of new vaccines and therapies to treat people who may someday be infected with an avian influenza virus that naturally mutates into a pandemic strain.

"This research could possibly help to contain a pandemic early on," he said.

Nabel's group focused on mutations that allow the H5N1 virus to better recognize and enter human cells, the press release said. To determine what mutations allow the virus to shift its adaptability, they compared proteins on the surface of the H5N1 virus, which are bird-adapted, with surface proteins on the human-adapted virus that caused the 1918 pandemic.

Focusing on genetic changes to one portion of the H5 protein, called the receptor binding domain, they found that as few as two mutations could enhance the ability of H5N1 to recognize human cells, according to the press release.

Nabel cautioned in the press release, however, that more mutations would likely be needed for the H5N1 virus to more easily spread between humans. He emphasized that the mutations he and his colleagues identified are probably just a subset of that dangerous group.

To assess how the immune system responds to the mutated H5N1 viruses the authors ran mouse studies, which revealed that mouse antibodies were 10 times less potent against the mutants. Then they created vaccines and isolated new antibodies that might be used to fight the mutated virus, the press release stated. When they vaccinated the mice, they identified one broadly reactive antibody that could neutralize both the bird- and human-adapted H5N1 virus forms.

The findings should improve H5N1 surveillance, Nabel said, because they make it easier for scientists to recognize dangerous mutations and identify structure-based vaccine candidates that might be more effective against the virus before it emerges.

"Insight into the structure of the avian flu virus has enabled us to target a critical region of HA [hemagglutinin] that directs its specificity," he said in the press release. "Such a structure-based vaccine design may allow us to respond to this future threat in advance of an actual outbreak."

Yang ZY, Wei CJ, Kong WP, et al. Immunization by avian H5 influenza hemagglutinin mutant with altered receptor binding specificity. Science 2007 Aug 10;317(5839):825-8 [Abstract]

See also:
Aug 9 NIAID press release

http://www3.niaid.nih.gov/news/newsreleases/2007/nabel_flu.htm

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/aug1007mutant.html

[Treyfish]

Re: New vaccine may beat bird flu before it starts

Scientists identify new targets for anti-flu drugs



Washington, Aug 16 : A team of researchers have discovered a potential new target for the development of anti-influenza (flu) drugs, including those that may be effective against potentially pandemic influenza strains like H5N1.

In the research, scientists at Cure Lab, Inc., a biotechnology company based in Canton, Massachusetts, worked in collaboration with researchers at Boston University and Harvard Medical School.

The potential drug target is the flu protein M2, long known to be highly conserved between avian and human strains of the virus. Scientists at Cure Lab found that this M2 protein may single-handedly kill human cells.

"This effect may constitute a previously unknown mechanism of influenza virus pathogenicity. If so, drugs that are shown to prevent M2-dependent cell killing have the potential to be used for the treatment of flu," said Dr. Alex Shneider, senior author on the paper and CEO of the company.

Membranes covering human and avian cells do not allow ions to move in and out of the cell freely, thus maintaining internal homeostasis. M2 protein of flu virus forms ion channels allowing ion trafficking into cells that cells no longer control.

Dr. Shneider and his group not only demonstrated that M2 kills mammalian cells, but also showed that ion channelling through M2 pores may be a molecular mechanism of this cell killing process.

"Developing drugs which block M2 ion channels could reduce or eliminate M2-induced cell death, and thus may be a new strategy for targeted development of anti-influenza drugs," Dr. Shneider said.

In collaboration with Dr. Vladimir L. Gabai from Boston University, and Dr. Shamil R. Sunyaev from Harvard Medical School scientist from Cure Lab, Inc. have developed mutant forms of M2 protein, where the ion channel is "blocked". The researchers have shown that these specific mutations they introduced in the protein significantly reduces its ability to kill the cell. From the point of view of the pharmaceutical industry and feasibility studies, introducing mutations into a protein, which mimic an effect of a future drug, is a way to validate the feasibility of a drug target.

Dr. Shneider said that an M2-targeted search for new anti-influenza drugs could lead to a new generation of medicines, which will complement those currently used for influenza disease prevention and treatment.

"This is especially important since an increasing number of influenza strains are becoming resistant to the drugs that are now widely used," Dr. Petr Ilyinskii, a principal scientist at Cure Lab and the first author on the paper said.

Their findings have been published in the August 15, 2007 issue of the journal Cell Cycle.
<!-- google_ad_section_end -->--- AN http://www.newkerala.com/july.php?ac...lnews&id=54196