Monoclonal Antibodies Can Provide Durable Immunity to Against Avian Flu and Other Flu


Researchers have discovered human antibodies that neutralize not only H5N1 bird flu but other strains of influenza as well and say they hope to develop them into lifesaving treatments.

Flu at wikipedia. Flu kills about 250,000 people every year. This can increase to 1-2 million during a pandemic. The spanish flu killed over 50 million This treatment could potentially be expanded to immunize against all flu and remove the threat of flu pandemic.

The antibodies — immune system proteins that attach to invaders such as viruses — also might be used to protect front-line workers and others at high risk in case a pandemic of flu broke out, the researchers said.

In tests on mice the viruses neutralized several types of influenza A viruses, including the H5N1 avian influenza virus, the researchers reported in Sunday’s issue of the journal Nature Structural & Molecular Biology.

“We were surprised and actually delighted to find that these antibodies neutralized a majority of other influenza viruses, including the regular seasonal (H1N1 strain of) flu,” Robert Liddington of the Burnham Institute for Medical Research in La Jolla, California, told reporters in a telephone briefing

UDPATE:

US News and world report has an interview that indicates the timing of the deployment of this work. 2010-2011 for clinical trials. 3-5 years for the research to make a universal flu vaccine and then another 2 years for that universal flu vaccine to get to clinical trials.

How do you know that this antibody works against both bird flu and seasonal flu?
We tested the antibody against bird flu, against 1918 pandemic flu; we tested it against all 10 different types of flu viruses, multiple strains, both in tissue culture and in animals. The antibody was not only active in preventing infection; you could give it to animals that got a lethal dose of the flu virus as late as three days after infection, when they were clearly getting sick, and they recovered and survived.

This is exciting science, but it’s not yet a cure for the flu. What’s the next step?
With the additional testing that’s required, there should be a very potent anti-influenza drug that will come out of this work. We are planning to be in clinical trials in the 2011-2012 flu season, which is about as fast as you can go. This is the actual drug that will wind up going into people. The antibodies are produced in cell factories. We need to pass our antibodies on to a manufacturer that will complete the animal studies and conduct the clinical trials.

How would this treatment work, if it’s approved as a flu treatment?
The antibodies have to be given by injection or inhalation, and they last in your body for 21 days. Monoclonal antibodies are currently being used to treat cancers and inflammatory diseases, including Herceptin for the treatment of breast cancer, Avastin or Erbitux for the treatment of colon cancer, and Retuxin for the treatment of lymphoma.

The other question is whether we can turn this into a universal vaccine. The research involved in making that next step will probably take three to five years. The goal will be to develop lifelong immunity to flu, rather than developing seasonal immunity as we do now.

The new antibodies attach to a less mutation-prone part of the virus, on the “stick” part of the lollipop, the researchers said. It appears to be similar across various strains.

“It forms part of a complex molecular machinery with many moving parts,” Liddington said. “All the parts must work perfectly together if the virus is to enter the cell and establish an infection.”

The antibodies gum up the works, the researchers found by making atomic images of the antibodies attacking the virus. They hope to use this knowledge to engineer or find other monocolonal antibodies that can neutralize the six strains of flu not affected by this latest discovery — including the H3N2 strain of seasonal flu now circulating.

Dr. Ruben Donis of the U.S. Centers for Disease Control and Prevention said the antibodies, called monoclonal antibodies because they attack one specific target only, protected mice from what should have been a lethal target of H5N1 avian flu virus — even up to three days later after infection.

“When we tried to select viruses that were resistant to the activity of these antibodies, we failed,” Donis told the briefing. “We could not get the virus to mutate and escape.”

Dr. Wayne Marasco of Dana-Farber said it should be straightforward to develop the antibodies as drugs, because they are already used broadly in cancer therapy.

A single injection protects for three weeks. “It provides durable immunity,” Marasco said.

Video Explaining the Spread of Flu and the Immune Response

A little over one minute into the two minute video is where antibodies are presented. After macrophages, T-cells and killer T-Cells.

FURTHER READING
Science Daily has coverage

Large quantities of monoclonal antibodies can be made relatively quickly, after more testing, these influenza-specific monoclonal antibodies potentially could be used in combination with antiviral drugs to prevent or treat the flu during an influenza outbreak or pandemic.

“One of the most remarkable findings of our work is that we identified a highly conserved region in the neck of the influenza hemagglutinin protein to which humans rarely make antibodies,” says Dr. Marasco. “We believe this is because the head of the hemagglutinin protein acts as a decoy by constantly undergoing mutation and thereby attracting the immune system to produce antibodies against it rather than against the pocket in the neck of the protein.”

Their findings could also assist vaccine developers.

He currently is arranging to use NIAID research resources to take the next steps: first, testing the antibodies in ferrets, the gold standard animal model for influenza, and then developing a clinical grade version of one antibody that could enter human clinical trials as soon as 18 months from when the development program begins. Should the antibodies prove safe and effective in humans, it could take several years to develop a licensed product.

The scientists also identified a new mechanism of antibody action against influenza: Once the antibody binds, the virus cannot change its shape, a step required before it can fuse with and enter the cell it is attempting to infect.

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1

So the China pollution and fuel efficiency choices are independent from California and US choices.

China's air pollution is still 70% within China.

As is California and the US air pollution. So California and US should clean up our air pollution because it will help 70% of air problem. On a separate track efforts should be made on the foreign 30%.

China is working on its air pollution problems. Recent WSJ article about increased wind energy target for China of 100GW by 2020. Somewhat beyond what was projected last year.

http://nextbigfuture.com/2007/05/beyond-three-gorges-dam-more-hydro.html

270 GW for hydro 2020
Wind 100-120GW by 2020
60GW for nuclear 2020
85GW natural gas, solar and biofuels

If China can increase energy efficiency and slow energy demand then over half of its energy for electricity could not be coal by 2020. About what the US is doing now. Within 12 years. Pretty good catchup.

2

Clearly if anyone is to enforce China's "strict" air quality regulations it would have to be the Chinese--which is what I meant in my earlier comment. Unfortunately, the chances of China actually doing that is close to zero.

California's squawling about this particular issue is largely a public distraction from the vastly more important issue of government mismanagement leading to energy shortages and a dropping revenue base. The loss of businesses (not just manufacturing) from California is an open secret that the morons who run the state still think they are hiding.

California is rearranging the deck chairs on the Titanic, and arguing over where the white chairs should go as opposed to the blue.

3

On this topic we obviously strongly disagree Al Fin. We agree on many things but not this.

As my article shows China does have stronger car fuel efficiency standards/laws than the US and California already.

Europe and Japan do as well.

Not pushing for greater efficiency has and will hurt the US car companies.

China's pollution is primarily from coal plants. Up until 2007, the US was generating more air pollution for decades. China can and should do more about its air pollution (building more hydro, nuclear, wind and solar and making some efforts to clean up coal). However, they are not a reason for the US not to do more for its own air pollution. Even if China "was forced" to clean up air pollution, this would not bring any manufacturing jobs back to the USA or California. Plus I do not see how China gets forced.

California has already shifted away from manufacturing other than for food processing (baking, wine, roasted nuts etc..), clothes (LA still generates a lot of fashion), computers and electronics, medical devices, airplanes. Fewer than 10% of California's jobs are manufacturing

http://www.netstate.com/economy/ca_economy.htm

http://www.ppic.org/content/pubs/jtf/JTF_EmploymentReviewJTF.pdf

http://www.labor.ca.gov/calBIS/cbbusincentives.pdf

california manufacturing jobs
http://www.calmis.cahwnet.gov/file/occguide-archive/engrobot.htm

4

The cost of fuel is higher in California than most other states for an excellent reason. Mis-management and over-regulation. The cost of energy in the US overall is higher than it needs to be for the same reasons. The US Congress has not gone as far over the cliff as the California State government, but it is on its way.

If they want to clean up the air of the left coast, they may want to look across the Pacific to China, which is pumping out so much soot and toxic waste into the air that it adds 15% of the pollution load to the left coast.

Try to get China to implement 1/10 of the clean air regulations of the US--AND ENFORCE THEM--and they might get a side benefit of cleaner air on this side of the Pacific.

5

The cost of fuel might do just as much to drive the remaining industries out of the state,as oppressive regulation.

The prevalent sprawl in CA and the rest of the United States in combination with poor fuel efficiency and high fuel prices, will be deadly to all of us here in the states. The problem with CA is that they have, truly, instituted so much absurd and destructive regulation that citizens and businesses are overly sensitized and very resistant to even appropriate regulations, such as this- for you really would think that most Americans would embrace greater fuel economy and conservation without this impetus.

Might I add that stringent conservation will become a matter of survival in the near future whether the regs mandate it or not?

As it is, we would need at least a decade to convert our entire fleet of autos and trucks to greater fuel efficiency, if the stricter standards went into effect tomorrow.

Europe and Japan, who have never had large supplies of petroleum of their own and have always had to conserve, have embraced vastly stricter standards because they know that their economic future depends upon their ability to conserve. We, on the other hand, seem lost in a dreamland where the oil keeps coming just because we want it to, and where reality will flex and bend into infinity just to accommodate our waste and sprawl.

Will oil have to go to $250 a barrel for us to wise up? Let's not let the squeals of the old, obsolete, hopelessly behind-it "American" automakers get in the way of improvements in efficiency that we know are necessary if we want to have motorized transportation on any terms going forward.

6

Unfortunately, Jerry Brown and Arnold Schwarzenegger know just enough about the economics of environmental regulation to drive out most of the profitable industries from California. Business-wise, the two are a devastatingly destructive duo for the future of the state.

Politically, though, they fit right in with the zeitgeist of suicidal over-regulation that is fashionable on the left coast. California is dying of mismanagement, and the "beautiful people" who run the state either do not see it or do not care.