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By pinpointing the window of opportunity when the human immune response to a particular pathogen peaks, scientists inside the US have developed a significantly faster way to isolate the highly specific antibodies needed to make flu vaccines. The discovery may also lead to new and faster ways to produce vaccines and therapies to fight numerous other illnesses.
The study is the function of researchers at Emory University School of Medicine, in Atlanta, Georgia, and Oklahoma Medical Investigation Foundation (OMRF), in Oklahoma City, and is published in the 30th April advanced on-line issue of Nature.
Co-author, Dr Rafi Ahmed, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar, stated:
“This approach could find broad application towards virtually any infectious illness.”
Corresponding author Dr Patrick Wilson, immunology researcher at the OMRF, stated:
“With just several tablespoons of blood, we can now rapidly generate human antibodies that can be utilised for immunization, diagnosis and treatment of newly emerging strains of influenza.”
“In the face of a disease outbreak, the ability to quickly produce infection-fighting human monoclonal antibodies would be invaluable,” he added.
The human body’s most efficient way of fighting illness is to be equipped with antibodies that can sense and neutralize invading pathogens. This can be the principle of vaccination: expose the body to a secure dose of the pathogen, the immune system detects it, and begins generating antibodies against it. Then when the “real” pathogen that is circulating (for instance seasonal flu) comes along, the immune system is ready to defend against the attack.
For the flu virus, experts get together every year to attempt and predict exactly which strains are going to be circulating within the coming season, along with the vaccine manufacturers can then prepare the flu shots. You can’t use last year’s vaccination formula because the flu virus, which is really a range of strains, mutates as it passes worldwide, from community to community, and last year’s antibodies no longer recognize the new strains.
There are currently two ways to “manufacture” the antibodies that are put inside the vaccines. The initial way is like finding a needle in a haystack. Scientists use blood from men and women who have been exposed to the specific strain the vaccine is destined for, after which “sift” through all of the similar antibodies until they find the one that is specific to that strain. This takes a long time, and in the meantime the virus is out there, evolving into new strains. The scientists also use models to attempt and predict the direction the mutations will take, but this can add to the timescale.
The second way to make antibodies for flu vaccines is to infect mice using the flu, take their antibody producing cells, make them suitable for humans, and use this “hybrid” to make antibodies. This way is faster, but less safe, simply because the human body could reject the mouse part of the hybrid in unforeseen ways.
The key discovery in this study, is that there is a window of opportunity following exposure to a pathogen exactly where the antibodies against that pathogen peak inside the bloodstream, and this makes it much easier to find them.
In this study the researchers had been able to pinpoint the exact influenza specific IgG+ antibody-secreting cell (ASC) circulating in blood plasma following a flu booster shot. They found that about 7 days after the vaccination, there was a small window of opportunity where there is a high level of this specific plasma cell inside the body, accounting for about 6 per cent of B cells inside the blood.
B cells are white blood cells that make antibodies. The immune system has distinct B cells ready to make antibodies against a range of pathogens that the body has been exposed to within the past.
The researchers had been able to distinguish these ASCs from influenza-specific IgG+ memory B cells that peaked 14 to 21 days after vaccination and averaged 1 per cent of all B cells. Memory B cells are what remain as a long term record of the exposure. The B cells that make the antibodies (the ASCs) recede, leaving just the memory cells as a record that the immune system has expertise of fighting that pathogen inside the past.
By pinpointing this window of opportunity when the ASCs levels peak, the researchers discovered that as much as 80 per cent of the purified ASCs harvested at this point had been influenza specific (they had a specific effect on B-cell receptors).
They had been able to sift by means of this a lot smaller pool of ASCs and produce more than 50 human monoclonal antibodies (mAbs) that bound to the 3 target flu strains with high affinity. Monoclonal antibodies (mAbs) are extremely specific antibodies (they bind to 1 strain of pathogen only) derived from a single parent immune cell (hence “clone”). The timescale from vaccination to mAbs production was one month, a lot faster than conventional strategies.
The researchers concluded that:
“The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared using the virus strain present within the vaccine.”
They discovered that OAS is not typical among normal healthy adults receiving the flu shot, as was previously believed. If you look at the right time, within the window of opportunity, you can see there is certainly a extremely specific response towards the current strain, which only later recedes and gets lost among all the earlier “memories” of prior strains.
While this study was part of a analysis effort to fight influenza, it has possible applications to any pathogen for which a vaccine exists, such as anthrax and smallpox.
“Vaccines can activate the immune system, but they require time to take impact, and many offer much less than 100 percent protection and carry risks of side effects,” stated Dr Stephen Prescott, president of the OMRF.
“With further analysis and testing, this new strategy may possibly permit a nurse going into the center of an outbreak to receive a shot to keep her secure from infection. Soldiers inside the field could keep a shot of anti-anthrax in their packs in case of a biological attack,” he added.
The approach also has possible to support individuals fight newly acquired and chronic diseases, by taking their antibodies, boosting them and giving them back again, or even to supply passive immunity against future infection.
“Rapid cloning of high-affinity human monoclonal antibodies against influenza virus.”
Jens Wrammert, Kenneth Smith, Joe Miller, William A. Langley, Kenneth Kokko, Christian Larsen, Nai-Ying Zheng, Israel Mays, Lori Garman, Christina Helms, Judith James, Gillian M. Air, J. Donald Capra, Rafi Ahmed & Patrick C. Wilson.
Nature advance on-line publication 30 April 2008.
DOI:10.1038/nature06890
Click here for abstract.
Sources: Oklahoma Medical Study Foundation, Emory University, journal abstract.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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