martes, 11 de enero de 2011

Pandemic Flu Offers Clue to Better Vaccines

Buenos días 

Este es un artículo sobre la gripe pandémica publicado en http://www.medpagetoday.com, interesante en cuanto a la vacuna.

 Al final tenemos el link donde fué publicado originalmente y pueden ver un video sobre el tema.

Saludos 

Dr. Carlos Erazo

By Michael Smith, North American Correspondent, MedPage Today
Published: January 10, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

The pandemic H1N1 influenza may have helped researchers solve a long-standing problem: how to make a flu vaccine that protects against multiple strains.

Such a vaccine is "the holy grail of influenza vaccinology," according to Patrick Wilson, PhD, of the University of Chicago, and colleagues.

But researchers have been frustrated because each influenza strain is just different enough from previous strains that a new vaccine has been needed every year, he told MedPage Today.

On the face of it, the 2009 pandemic strain was no improvement -- it was markedly different from all earlier H1N1 strains, and vaccines had to be painstakingly developed in the same way the seasonal flu vaccines are made.
Action Points  
  • Explain that researchers found broadly cross-reactive antibodies to more than the rapidly changing hemagglutinin protein when analyzing blood from patients who had H1N1 pandemic influenza infection.
  • Note that the investigators suggested that these antibodies arose from memory B cells and could provide an avenue for development of a cross-protective influenza vaccine that might not have to be administered yearly.
But, Wilson and colleagues reported in the Jan. 10 issue of the Journal of Experimental Medicine, the very novelty of the virus may have opened the door to better vaccines.
An analysis of immune responses of a handful of patients infected with the pandemic strain, Wilson and colleagues reported, allowed the researchers to isolate and clone antibodies that not only neutralized the 2009 virus, but also a range of other H1N1 strains, including the highly pathogenic 1918 strain.
"The surprise was, when we made these antibodies, that they were unusually broadly reactive," Wilson said.
Current vaccines target a section of the viral hemagglutinin protein, the so-called globular head, which is highly variable. But more than half of the antibodies found by the researchers bound to regions in the stalk of the protein, which is thought to be more highly conserved, Wilson said.
Interestingly, however, some antibodies found in the study did bind to the head of the protein and even they were broadly neutralizing, suggesting that their binding regions are also highly conserved over time, Wilson said.
Using those highly conserved regions, it might be possible to create a flu vaccine that would protect year after year, he said.
"With the proper immunogen," the researchers argued, "the long-sought development of a pan-influenza vaccine might be possible."
Wilson and colleagues are currently analyzing immune responses to the monovalent H1N1 vaccine to see if the vaccinated people have similar antibodies to those who actually had the infection, he said.
The origin of the antibodies, the researchers think, may be memory B cells in the patients that were created during previous exposures to different flu strains -- a small part of a host of responses to various antigens, including the usual suspects on the globular head.
Evidence for that, they said, may be the fact that the cells have highly mutated immunoglobulin genes, indicating extensive affinity maturation, the process that over time improves how well antibodies match an antigen.
The novel pandemic strain, however, was sufficiently different that only the rare antibodies to the conserved regions had targets, so they were preferentially amplified.
Interestingly, Wilson and colleagues said, the one antibody they found that is highly specific for the pandemic strain was derived from the patient with the most severe illness. The specificity combined with the severity of the illness suggests, they said, that he had no preexisting immunity to previous strains.
As a sidelight on the discovery, the monoclonal antibodies created by the researchers appear to have both preventive and therapeutic possibilities in mice.
Given before infection, the researchers found, they were highly effective at preventing death in animals from a lethal dose of a mouse-adapted version of the H1N1 pandemic strain.
On the other hand, mice injected with a lethal dose of the pandemic strain could be rescued by a bolus of antibodies, even as much as 60 hours after infection, and well after they had developed symptoms, the researchers reported.
In one experiment, mice were given the antibodies 48 hours after infection. But six days after infection, the virus was either undetectable or barely detectable. Meanwhile, control animals had all died by day seven or eight, they reported.

The study was supported by the National Institutes of Health, the Northeast Biodefense Center, and the National Foundation for Cancer Research. The authors said they had no financial or commercial conflicts of interest.
http://www.medpagetoday.com/InfectiousDisease/SwineFlu/24253?utm_content=GroupCL&utm_medium=email&impressionId=1294731282824&utm_campaign=DailyHeadlines&utm_source=mSpoke&userid=188864

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