Antibodies still protect 1918 flu survivors

[AlaskaDenise]

Maggie Fox, Health and Science Editor , Reuters

Published: Sunday, August 17, 2008

WASHINGTON (Reuters) - Antibodies from survivors of the 1918 flu pandemic, the worst in human memory, still protect against the highly deadly virus, researchers reported on Sunday.

The findings by a team of influenza and immune system experts suggest new and better ways to fight viruses -- especially new pandemic strains that emerge and spread before a vaccine can be formulated.
These survivors, now aged 91 to 101, all lived through the pandemic as children.

Their immune systems still carry a memory of that virus and can produce proteins called antibodies that kill the 1918 flu strain with surprising efficiency, the researchers report in the journal Nature.

"It was very surprising that these subjects would still have cells floating in their blood so long afterward," said Dr. James Crowe of Vanderbilt University in Tennessee, who helped lead the study.

The antibodies also protected mice from the 1918 virus, which swept around the world at the end of World War One killing between 50 million and 100 million people, Crowe's team reports in the journal Nature.

"The antibodies that we isolated are remarkable antibodies. They grab onto the virus very tightly and they virtually never fall off," Crowe said in a telephone interview.

"That allows them to kill the 1918 virus with extreme potency, meaning it takes a very small amount of antibody."

The human body has two systems for fighting off bacterial and viral invaders. One system uses so-called T-cells while the other employs B-cells, made in the bone marrow, which in turn make antibodies to both flag and directly attack the targets.

RESURRECTED VIRUS

Dr. Christopher Basler and colleagues at the Mount Sinai School of Medicine in New York tested the 1918 survivors and found that in most of them, the B-cells made antibodies highly attuned to the 1918 flu strain.

Dr. Terrence Tumpey at the U.S. Centers for Disease Control and Prevention had worked on a team that resurrected the 1918 virus taken from buried victims of the epidemic and tested this virus in mice. Mice given the antibodies from the elderly survivors lived, while those given placebos died.

Crowe said it will now be important to test other people who have had influenza to see if their immune responses are as strong. "The thought is the first influenza that you see during life is the one that you have the best immunity to," he said.

"If we can learn the rules about how these antibodies work we may be able to design antibodies to lots of other viruses."

The 1918 flu was an H1N1 strain that apparently came straight from birds(???). "This study tells us that human beings can make long lasting immune responses to bird influenza," Crowe said.

Crowe said his team is working to get antibodies from people vaccinated with experimental shots for the H5N1 avian influenza now circulating in Asia, Europe, the Middle East and Africa. H5N1 mostly affects birds but it has infected 385 people since 2003, killing 243.

Experts fear that, like the H1N1 virus did in 1918, H5N1 will mutate into a form that passes easily among people and spark another pandemic. No one knows if the vaccines being made now would protect against whatever form of H5N1 might emerge.

Crowe said antibodies from survivors might make a good interim treatment while a vaccine is formulated, manufactured and distributed -- a process that would take months.

http://www.canada.com/topics/bodyandhealth/story.html?id=78406614-9910-47a4-a90c-f590e096c104

 

[HenryN]

Re: Antibodies still protect 1918 flu survivors

The antibodies were reported in 2004.

 

[AlaskaDenise]

Re: Antibodies still protect 1918 flu survivors

Didn't those past reports say the antibody levels were about 1000 times normal? That fact has always stuck in my mind as very significant - I've often wondered why they are still so high.

What is your take, Dr. Niman, on why those antibody levels are still so high?

.

 

[Giuseppe]

Re: Antibodies still protect 1918 flu survivors

Here is an image captured from a presentation by Yoshiro Kawahoka.

 

[Giuseppe]

Re: Antibodies still protect 1918 flu survivors

I have at least three presentations from 2004 or earlier that reported investigation about 1918 re-created antibody response in human and animal models (HA / NA neutralization titers / cross-reactions):

1) H5N1 avian influenza viruses - Viruses possessing the 1918 virus HA and NA - University of Wisconsin - Yoshihiro Kawaoka

2) Characterization of the 1918 influenza virus - Collaborative effort among different research groups and institutions - -Armed Forces Institute of Pathology, Washington DC Jeffery K. Taubenberger - -Mount Sinai School of Medicine, New YorkAdolfo Garc?a-Sastre - Peter Palese - Christopher F. Basler - -CDCTerrence M. Tumpey - -USDA, Athens, Georgia David E. Swayne - -University of Washington, SeattleMichael G. Katze - -Scripps Research Institute, La JollaIan A. Wilson - NIH/NIAID support: P01 AI0581113

3) Application of Reverse Genetics to Influenza Vaccine Development
Kanta Subbarao Laboratory of Infectious Diseases NIAID, NIH

Another flurry of recycled news / publication fanfare about well known researches (!?)

 

[Sally Furniss]

Re: Antibodies still protect 1918 flu survivors

1918 Pandemic - Data, stories & history

http://www.flutrackers.com/forum/forumdisplay.php?f=552

 

[AlaskaDenise]

Re: Antibodies still protect 1918 flu survivors

Survivors of 1918 Flu Pandemic Immune 90 Years Later

Finding could lead to new strategies for fighting future pandemics, researchers say

SUNDAY, Aug. 17 (HealthDay News) -- People who lived through the 1918 flu pandemic that killed 50 million worldwide are still producing antibodies to the virus 90 years later, researchers report.

"Most people have a notion that elderly people have very weak immunity or they have lost immunity," said lead researcher Dr. James E. Crowe Jr., a professor of pediatrics, microbiology and immunology at Vanderbilt University.

"This study shows that extremely elderly people have retained memory of being infected with the 1918 flu, even 90 years later," Crowe said.

This is the first evidence that shows that people developed significant immunity to the 1918 flu virus, Crowe said. "It's important to know that you can develop immunity to such a pandemic virus. That has implications for new pandemic viruses," he said.

The report is published in the Aug. 17 issue of Nature.

For the study, Crowe's team studied antibodies in the blood of 32 people in their 90s and 100s, born during or before 1915. They found that all 32 people had antibodies to the 1918 strain of flu virus. In fact, several of these people were still producing the antibodies to the virus.

In experiments with mice, the researchers found that these antibodies continue to protect the mice from infection with the 1918 flu strain.

The study also shows that people have a "surprising ability" to maintain immunity to things they saw a long time ago, Crowe said.

Whether this long-term immunity is peculiar to the 1918 flu virus isn't known, Crowe said. He believes more work needs to be done understand the full extent of this immune response. "The elderly might be a very good donor source for finding antibodies against viruses," he said.

"This study shows that humans can develop very potent immune responses against dangerous influenza that cause pandemics," Crowe said. "It gives us hope that we can develop vaccines and antibody treatments for any other pandemic viruses that come along," he said.


Dr. Marc Siegel, an associate professor of medicine at New York University School of Medicine in New York City, thinks that people who developed this strong immune response may have been infected with a less deadly strain of flu before 1918.

"The implication of this study is the 1918 virus was so powerful that the immunity you had to have in order to survive was so prominent that it lasted for the rest of your life," Siegel said.

However, Siegel noted that some people may have had experience with a similar less deadly flu virus that prepared their immune system to handle the 1918 strain.

"So, those in certain age groups who had seen a related virus had the strongest responses," Siegel said. "Either they died, or they developed a profound immune response," he said.

Siegel expects if there is another flu pandemic, some people will develop a lifelong immunity as they did in 1918.

More information
For more on avian flu, visit the U.S. Centers for Disease Control and Prevention.

 

[AlaskaDenise]

Re: Antibodies still protect 1918 flu survivors

Kawahoka's presentation appears to show that 1898 and 1899 were the optimum years to be born.......so is there any firm concensus on which strain caused the pandemics in those years? I've read different reports, although most say H2N2 - so why would an H2N2 confer strong immunity to H1N1?

Ref earlier FT discussion: http://flutrackers.com/forum/showthread.php?t=10311

.

 

[gsgs]

Re: Antibodies still protect 1918 flu survivors

but then, those who were infected in the 2nd wave
didn't even have much protection for the 3rd wave
in early 1919. Also no protection from wave 1 to wave 3.
Some protection from wave 1 to wave 2

 

[mixin]

Re: Antibodies still protect 1918 flu survivors

And then we see this from the historical document I've been summarizing:
"...it is only when one looks back that the two big classes?
800 out of every 1,000, mild and ordinary;
200 out of every 1,000 severe, pulmonary, grave?
emerge clearly into view."

So it didn't appear to be severe for anyone except for the 20% with lung problems.

 

[HenryN]

Re: Antibodies still protect 1918 flu survivors

Remembrance of viruses past

Long-lived survivors of the 1918 flu pandemic may hold the key to defeating future outbreaks.
Heidi Ledford
<!-- -->Nearly a century after the 1918 influenza pandemic claimed 50 million lives, survivors continue to produce powerful antibodies against the virus, researchers have found.

The 1918 flu pandemic filled military barracks with victims.U.S. Naval Historical Center
These antibodies have now been isolated from their nonagenarian hosts and could be exploited to defend against future outbreaks. In work published this week in Nature<SUP>1</SUP>, researchers report that five of the antibodies were able to rescue mice that had been infected with the 1918 flu virus.
Antibodies attach themselves to viral proteins and, ideally, neutralize the virus. But antibodies vary widely in the specific proteins or regions within a protein that they bind. Researchers can take advantage of this to learn more about weaknesses in the virus: the regions targeted by an antibody could also make a good target for a vaccine or drug.
Despite this, no one had yet characterized the antibodies in survivors of the 1918 pandemic. Eric Altschuler, now a doctor of physical medicine and rehabilitation at the University of Medicine and Dentistry of New Jersey, was inspired to do so after watching a television show one night while on call as a medical resident. (?It was a slow night,? he says.) The show was a short-lived series called 'Medical Investigation', and featured fictional scientists who track down the causes of mysterious disease clusters.
In the episode he watched that night, scientists respond to an outbreak of a lethal virus that curiously spares an elderly butler who had survived the 1918 flu pandemic. The investigators realize the culprit is a flu virus similar to the 1918 strain, and give an ailing heroine a transfusion of blood from the butler just in time to save her life. "It?s TV," says Altschuler, "so everything worked out in about an hour." His own efforts to replicate the programme?s result in mice ? admittedly with considerably more detailed analysis along the way ? would take about four years.
Long-life antibodies

With little immunological training of his own, Altschuler recruited a research team including microbiologist Christopher Basler of Mount Sinai School of Medicine in New York, who had worked on the reconstruction of the 1918 flu virus, and immunologist James Crowe of Vanderbilt University in Nashville, Tennessee. The team gathered blood samples from 32 people aged 91 to 101 years.
Many of the participants remembered having a sick relative during the pandemic. ?It was a horrible time and unfortunately many people can recall that,? says Altschuler. ?We met people who had multiple relatives die on the same day.?
The researchers found that 94% of the participants produced antibodies that neutralized the 1918 virus. In contrast, only one out of ten people born after the pandemic produced such antibodies.
Scientists had expected the influenza antibodies to be long-lived. ?But it?s never been demonstrated in this capacity,? says Michael Gale, an immunologist at the University of Washington in Seattle who was not affiliated with the study. ?This is a true demonstration that neutralizing antibodies can persist for many decades.?
The researchers went on to infect mice with the reconstructed 1918 flu virus and then treated them with the antibodies. Like the heroine from the television show, mice that received the antibodies survived the infection. Those that did not invariably succumbed.
Altschuler's team also isolated antibody-producing cells, generating five cell cultures that each produced a single type of antibody and could be grown in the lab. When they studied the sequence of the genes that encoded these antibodies, the scientists found they had accumulated many mutations - suggesting that the cells had made further adaptations to similar viruses after 1918, says Gale.
The results suggest that the antibodies could be used therapeutically should an outbreak of a similar virus occur. What?s more, one of the antibodies reacted not only with the 1918 flu strain, but with several other strains as well. "It?s probably binding to something that?s really important for the flu virus ? possibly so important that the virus can?t change it to avoid immunity," says immunologist Patrick Wilson of the University of Chicago. "As a target for drug development, that would be ideal."

• References
  1. Yu, X. et al. Nature doi:10.1038nature07231 (2008).

 

[gsgs]

Re: Antibodies still protect 1918 flu survivors

were those 32 people sick with flu in 1918 or later ? which wave ?

those who had flu in 1922-1930, did they develope weaker immunity ?

how about 1957,1968 then ?

 

[Giuseppe]

Re: Antibodies still protect 1918 flu survivors

Abstract and free full text PDF file attached at: http://www.flutrackers.com/forum/showpost.php?p=174864&postcount=1

 

[JJackson]

Re: Antibodies still protect 1918 flu survivors

I remember this from the first time around and was not sure then - and am still not clear - why this is particularly important.
Most viruses change so rapidly (and flu certainly does) that it is most unlikely that an antibody to a virus circulating a century ago is going to be of much use now. Even if I time traveled back from the future with a survivor of an H5N1 pandemic and said "the pandemic starts in one year from today" we do not currently have the equipment to do much about it. The more interesting anti-bodies are circulating in the blood of those unfortunate souls who have survived AI H5N1, at least they have a fighting chance of being close to any eventual pandemic strain.
Or did I miss something important?

 

[Giuseppe]

Re: Antibodies still protect 1918 flu survivors

I remember this from the first time around and was not sure then - and am still not clear - why this is particularly important.
Most viruses change so rapidly (and flu certainly does) that it is most unlikely that an antibody to a virus circulating a century ago is going to be of much use now. Even if I time traveled back from the future with a survivor of an H5N1 pandemic and said "the pandemic starts in one year from today" we do not currently have the equipment to do much about it. The more interesting anti-bodies are circulating in the blood of those unfortunate souls who have survived AI H5N1, at least they have a fighting chance of being close to any eventual pandemic strain.
Or did I miss something important?

The importance resides - among the others - in the particular potency, shape and effectiveness of these antibodies and of the precursor lymphocite B cells to react when in contact with an engineered version of H1N1 similar to Spanish flu. These B cells react as the infection occurred a few years ago and they were collected in living very old people.

Thus, some not yet unravelled properties reside both in 1918 HA and NA surface proteins and in people who born earlier than 1915 and in the viruses their contracted previously the great pandemic.

Whether this research may add something in current fight against H5N1 panzootic it is hard to predict.

But perhaps in future a novel proteic structure of 1918 HA and NA will be available to allow a more in depth study of viral-host interactions or for design novel inhibitory compounds.

 

[mixin]

Re: Antibodies still protect 1918 flu survivors

I saw this additional info mention of swine flu

These antibodies reacted strongly to the 1918 virus and cross-reacted with proteins from the related 1930 swine flu but not to more modern flu strains.

http://www.news-medical.net/?id=40760