Pandemic Flu Use? Human Monoclonal Antibodies - Scientists Find a Quicker Way to Make Against Flu

[Gert van der Hoek]

Public release date: 30-Apr-2008


NIH/National Institute of Allergy and Infectious Diseases

Researchers find quick way to make human monoclonal antibodies against flu

Human monoclonal antibodies (mAbs)--highly specific, identical, infection-fighting proteins produced in large quantities in the lab in cell lines that are derived from a single cell--against influenza can be rapidly produced in the lab, according to a new report from scientists supported by the National Institutes of Health (NIH). Using cells drawn from volunteers inoculated with seasonal influenza vaccine, the investigators made influenza-specific mAbs in just a few weeks rather than the typical two to three months. The new technique could potentially be used to rapidly create mAbs for a range of uses, the team says.

Rafi Ahmed, Ph.D., and Jens Wrammert, Ph.D., of Emory Vaccine Center of the School of Medicine, Atlanta, and their coworkers collaborated with Patrick Wilson, Ph.D., and J. Donald Capra, M.D., and others from the Oklahoma Medical Research Foundation, Oklahoma City. They describe their new method in an advance online publication in Nature. The research was supported by the NIH?s National Institute of Allergy and Infectious Diseases (NIAID) and National Center for Research Resources (NCRR).

The first therapeutic mAb was approved for human use in 1986 and there are now more than 20 Food and Drug Administration-approved mAbs, including two human mAbs, most of which are used to treat certain cancers or immunological diseases. Human mAbs have long been envisioned as possible treatments for acute or chronic infections, but various technical barriers have slowed their development.

?With this new technique for making human monoclonal antibodies efficiently and quickly, Drs. Wilson and Ahmed and their colleagues have made a significant advance,? says NIAID Director Anthony S. Fauci, M.D. ?Their accomplishment opens the way to producing mAbs that potentially could be used diagnostically or therapeutically not only for influenza but for other infectious diseases as well.?

In addition to being relatively quick to make, the influenza mAbs also bound tightly to virus strains in the seasonal influenza vaccine, the scientists determined. Such high affinity for the vaccine?s viruses suggests that the mAbs would also bind well to the circulating viruses targeted by the vaccine and thus could be used either as a therapy or as a way to diagnose the strain of influenza virus an individual is infected with, say the investigators.

The mAbs made in this study were not tested on influenza virus strains with pandemic potential, such as the H5N1 subtype that causes so-called bird flu. Nevertheless, notes Dr. Ahmed, the ability to make high-affinity influenza mAbs quickly raises the possibility of deploying them in combination with other disease control strategies in the event of a global influenza pandemic. According to Dr. Ahmed, the group is now planning to use their technique to generate mAbs against H5N1.

To make the new influenza mAbs, the researchers first inoculated volunteers with seasonal influenza vaccine. The scientists wanted to know if a subset of immune system cells called antibody-secreting plasma cells (ASCs) could serve as a source of mAbs. ASCs are the body?s first responders, churning out a surge of antibodies as part of the initial reaction to infection or vaccination. ASC activity is swift but brief. In this study, ASC responses peaked at one week after vaccination, then dropped sharply and were barely detectable after two weeks. The Emory University researchers found a way to capture the fleeting ASCs that produce the initial wave of influenza-specific antibodies. Importantly, says Dr. Ahmed, as many as 80 percent of the purified ASCs produced influenza-specific antibodies.

Dr. Wilson and his coworkers at the Oklahoma Medical Research Foundation used the vaccine-generated, influenza-specific ASCs to create the mAbs. Only a few weeks elapsed between vaccination of the volunteers and purification of human mAbs with a high affinity for influenza virus. ?With just a few tablespoons of blood, we can now rapidly generate human monoclonal antibodies that potentially could be used for diagnosis and treatment of newly emerging strains of influenza,? says Dr. Wilson. ?In the face of a disease outbreak, the ability to produce infection-fighting human mAbs swiftly would be invaluable.?

The technique developed by the Emory University and Oklahoma Medical Research Foundation scientists is not limited to the production of mAbs for influenza, and the team is currently working to make mAbs for other disease agents. ?This research holds clinical potential for a host of infectious diseases including anthrax, respiratory syncytial virus and pneumococcal pneumonia,? says Dr. Capra.


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For more information on information about influenza, visit http://www3.niaid.nih.gov/healthscie...lu/default.htm.

NIAID is a component of the NIH. 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.

NCRR, also a component of NIH, provides laboratory scientists and clinical researchers with resources, tools and training they need to understand, detect, treat and prevent a wide range of diseases. NCRR also supports basic, translational and applied research on variety of diseases through resource building. The research highlighted here was supported, in part, by NCRR?s Institutional Development Awards Program, which helps build research infrastructure to enhance institutions? research capacity and competitiveness for NIH grants.

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 http://www.nih.gov.

Reference: J Wrammert et al. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature DOI: 10.1038/nature06890 (2008).

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

http://www.eurekalert.org/pub_releases/2008-04/nioa-rfq042808.php

[gsgs]

Re: Researchers find quick way to make human monoclonal antibodies against flu

how much is "invaluable" in Euros ?

[Shiloh]

Re: Researchers find quick way to make human monoclonal antibodies against flu

Source: http://arstechnica.com/journals/scie...om-its-victims

Fighting the flu with antibodies from its victims

By John Timmer | Published: April 30, 2008 - 12:21PM CT

Anyone who has followed the concern with which the medical community greeted recent bird flu outbreaks will realize that it and other emerging diseases have raised the specter of a modern pandemic. The flu pandemic of 1918 killed an estimated 50 million people globally; the increase in population and transportation links that have occurred since would mean a modern equivalent would be far more deadly. Now, researchers may have found a way to generate antibodies to limit the spread of a virus by using the immune systems of its victims.

Viruses like the flu have a nasty habit of evolving rapidly, which limits the effectiveness of both immunizations and antiviral drugs. The situation is even worse for viruses we know less well, as no work has been done to develop vaccines. The new research attempts to get around these problems by having the immune systems of a virus' victims do the hard work of generating an antiviral reagent for us.

The researchers worked with people who had been given a flu vaccine, and explored the production of antibody-secreting B cells in the days following the vaccination. They found that, by a week later, cells producing antibodies that targeted the flu virus made up about six percent of the total B cells in the blood. Selecting for cells that secreted antibodies allowed them to isolate a population in which an average of 70 percent of the cells made antibodies against the virus.

Scientists have already developed techniques that can use these cells to manufacture large amounts of antibodies. Human antibodies won't cure a viral infection, but they may help slow its spread long enough to allow a victim's own immune system to get the infection under control. Most importantly, a human antibody is far less likely to set off an anaphylactic shock response when injected into a person, unlike antibodies made by animal cells.

Putting this technique to effective use won't be simple?health authorities will have to isolate antibody producing cells from those with infections for each new strain of a virus that comes along if they want to be prepared for a pandemic. Still, it the first indication I've seen that someone investigating a new virus outbreak can take active steps to prepare for it becoming a problem.

Nature, 2008. DOI: 10.1038/nature06890 http://www.nature.com/nature/journal...D35D78D5C945D3

[Nancy]

Scientists find a quicker way to make antibodies

Scientists find a quicker way to make antibodies
Wed Apr 30, 2008 4:27pm EDT
By Julie Steenhuysen

CHICAGO, April 30 (Reuters) - A new process to extract and copy the essential elements of cells that make human antibodies has provided a shortcut to making targeted, infection-fighting proteins known as monoclonal antibodies, U.S. researchers said on Wednesday.

The process allowed them to make influenza-specific antibodies in as little as a month, and they said the discovery could lead new treatments for other infectious diseases such as hepatitis C, pneumococcal pneumonia or anthrax.

It could even be used in an influenza pandemic to protect health workers until a vaccine could be made, they said.

"With just a few tablespoons of blood, we can now rapidly generate human antibodies that can be used for immunization, diagnosis and treatment of newly emerging strains of influenza," said Patrick Wilson, an immunology researcher at the Oklahoma Medical Research Foundation, whose study appears in the journal Nature.

"In the face of a disease outbreak, the ability to quickly produce infection-fighting human monoclonal antibodies would be invaluable," Wilson said in a statement.

Antibodies are immune system proteins that recognize and help orchestrate an immune attack on bacteria, viruses and parasites. Monoclonal antibodies are specially engineered to attack a certain protein.

But making them is laborious, involving sifting through white blood cells known as B cells to find the needed antibody or vaccinating mice and altering their antibodies to look like human antibodies. It can take years.

"A better approach would be to have a way to very quickly generate monoclonal antibodies at a very high efficiency," Wilson said in a telephone interview.

He said they had succeeded in doing so.

"We can go from vaccine to antibody in just a month. That is the surprise," Wilson said.

'BURST OF CELLS'

To make the antibodies, the researchers vaccinated volunteers against seasonal flu. Then they examined a type of immune system cell known as antibody-secreting plasma cells, which produce a surge of antibodies as part of an initial response to infection.

Wilson and colleagues were able to capture and purify these cells, and they found as many as 80 percent of these purified antibodies were flu-specific.

He said the finding could lead to emergency treatments for a pandemic influenza, or to treat people with seasonal flu.

"We now can take these cells and quickly go to antibodies," said Wilson, who worked on the project with scientists at Emory University in Atlanta.

While it has not yet been tested against potential pandemic strains of influenza, such as the H5N1 strain that causes bird flu, those studies are underway, Wilson said.

The process also could be used to make antibodies for hepatitis C or antibiotic-resistant infections or even for human immunodeficiency virus or HIV, the virus that causes AIDS.

And the method could be used to generate fully human monoclonal antibodies for cancer and immune disease treatments such as Genentech Inc's (DNA.N: Quote, Profile, Research) breast cancer drug Herceptin and Johnson & Johnson's (JNJ.N: Quote, Profile, Research) Remicade for rheumatoid arthritis and other immune diseases.

There are more than 20 monoclonal antibody-based therapies approved in the United States, and hundreds more are in development. Most are made from mouse antibodies, which can cause an allergic reaction in some people.

"It allows the world to have a new opportunity to generate many antibodies to many different things," Wilson said. (Editing by Maggie Fox and Xavier Briand)

http://www.reuters.com/article/latestCrisis/idUSN30538248

[sharon sanders]

Re: Pandemic Flu Use? Human Monoclonal Antibodies - Scientists Find a Quicker Way to Make Against Flu

"...A new process to extract and copy the essential elements of cells that make human antibodies has provided a shortcut to making targeted, infection-fighting proteins known as monoclonal antibodies, U.S. researchers said on Wednesday.

The process allowed them to make influenza-specific antibodies in as little as a month, and they said the discovery could lead new treatments for other infectious diseases such as hepatitis C, pneumococcal pneumonia or anthrax.

It could even be used in an influenza pandemic to protect health workers until a vaccine could be made, they said.

'With just a few tablespoons of blood, we can now rapidly generate human antibodies that can be used for immunization, diagnosis and treatment of newly emerging strains of influenza,' said Patrick Wilson, an immunology researcher at the Oklahoma Medical Research Foundation,.."

[JJackson]

Re: Pandemic Flu Use? Human Monoclonal Antibodies - Scientists Find a Quicker Way to Make Against Flu

Now all we need is the industrial scale production, agreements on the use of various patented process, intellectual copyright wavers, material transfer agreements, silent lobby groups for other processes, lots of money, goodwill to all men, a fair wind & a partridge in a pear tree.

[gsgs]

Re: Pandemic Flu Use? Human Monoclonal Antibodies - Scientists Find a Quicker Way to Make Against Flu

I think, vaccine would be much cheaper

[JJackson]

Re: Pandemic Flu Use? Human Monoclonal Antibodies - Scientists Find a Quicker Way to Make Against Flu

gsgs:<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p>
<o:p></o:p>
What vaccine for what purpose and produced by what method?<o:p></o:p>
<o:p></o:p>
Seasonal flu vaccine requires X doses ordered several months in advance for delivery at a known time with annual repeat orders - Failure to supply would lead to an increased number of deaths in the young and old but the increase would not be noticed by the general public and may only be apparent statistically.<o:p></o:p>
<o:p></o:p>
Pandemic flu vaccine requires 50X doses for immediate delivery with the possibility of a repeat order in about 30 years - Failure to supply could be either as above or catastrophic but we will not know which until after the event.<o:p></o:p>
<o:p></o:p>
Chalk & Cheese.<o:p></o:p>

[gsgs]

Re: Pandemic Flu Use? Human Monoclonal Antibodies - Scientists Find a Quicker Way to Make Against Flu

1) prepandemic vaccine as recently ordered by HHS, Qinghai strain, $5 per dose
for all US-citizens
2) advance purchase agreement (APA) with vaccine producers for strain-specific vaccine in case of
a pandemic to be delivered after 4-5 months in a pandemic.
the prepandemic vaccine can be given as first dose ("mock up") immediately.
It will produce some cross-protection depending on the strain.
In connection with the 2nd strain-specific dose it should probably work almost as well
as two specific doses.

Switzerland and others(Singapore,Austria,Denmark?,Ireland?,.. )did it for 100% of their population
UK has planned/ordered it for 50% of the population other EU-countries have similar
solutions. USA mainly relies on their capacities to be completed 2010,2011

I don't know, what 2) costs. The agreement alone without production, maybe $10 per dose.
1) may have to be renewed after 3? years
in 2008 other solutions become available, capacity is bigger, prices lower.


Some expensive antibody-doses for health care personnell etc. could then quickly be produced
when/if panflu starts.
But I assume the bulk will still be vaccine. I.e. for poorer countries.
Provided the vaccine works well, of course - better have several options

[JJackson]

Re: Pandemic Flu Use? Human Monoclonal Antibodies - Scientists Find a Quicker Way to Make Against Flu

gsgs
I have writen a reply to your post but as I expanded it to cover overlapping issues in another thread, which links to this one, I have posted it there and linked from here to save duplication.

http://www.flutrackers.com/forum/showthread.php?p=153502#post153502