Discovery of natural antibody brings a universal flu vaccine a step closer

[Shiloh]

Source: http://www.eurekalert.org/pub_releases/2011-07/sri-don070711.php

Public release date: 7-Jul-2011
[
Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute

Discovery of natural antibody brings a universal flu vaccine a step closer
An academic-industry collaboration by Scripps Research and Crucell finds broadly acting antibody against influenza viruses

LA JOLLA, CA ? July 7, 2011 ? Annually changing flu vaccines with their hit-and-miss effectiveness may soon give way to a single, near-universal flu vaccine, according to a new report from scientists at The Scripps Research Institute and the Dutch biopharmaceutical company Crucell. They describe an antibody that, in animal tests, can prevent or cure infections with a broad variety of influenza viruses, including seasonal and potentially pandemic strains.

The finding, published in the journal Science Express on July 7, 2011, shows the influenza subtypes neutralized with the new antibody include H3N2, strains of which killed an estimated one million people in Asia in the late 1960s.

"Together this antibody and the one we reported in 2009 have the potential to protect people against most influenza viruses," said Ian Wilson, who is the Hansen Professor of Structural Biology and a member of the Skaggs Institute for Chemical Biology at Scripps Research, as well as senior author of the new paper with Crucell's chief scientific officer Jaap Goudsmit.

Tackling a Major Shortcoming...

 

[tetano]

Antibody Discovery AdvancesUniversal Flu Vaccine Goal

Antibody Discovery AdvancesUniversal Flu Vaccine Goal

The Holy Grail of flu vaccines -- a universal vaccine -- is drawing close, say researchers who today report discovery of an antibody effective against wide varieties of influenza viruses, including seasonal and potentially pandemic strains.

The antibody is similar to another, CR6261, which is about to begin human clinical trials by the biotech company Crucell, which collaborated on the study. The new antibody may be even more effective than CR6261, which showed great efficacy in mice.

In mice, injecting the CR6261 antibody prevented or cured an otherwise-lethal infection by about half of flu viruses. These include the infamous H1 viruses such as H1N1, the so-called swine flu, strains of which caused a deadly pandemic in 1918, and a much less severe but worrisome outbreak in 2009.

The study, "A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses," was published in the journal Science Express on July 7, 2011. Ian Wilson, a professor of structural biology at The Scripps Research Institute, was senior co-author of the paper, along with Jaap Goudsmit, chief scientific officer of Crucell.

More from the Scripps press release:

"Wilson's laboratory has been working with Crucell scientists since 2008 to help them overcome the major shortcoming of current influenza vaccines: They work only against the narrow set of flu strains that the vaccine makers predict will dominate in a given year, so their effectiveness is temporary. In addition, current influenza vaccines provide little or no protection against unforeseen strains.

"These shortcomings reflect a basic flu-virus defense mechanism. The viruses come packaged in spherical or filamentous envelopes that are studded with mushroom-shaped hemagglutinin (HA) proteins, whose more accessible outer structures effectively serve as decoys for a normal antibody response. "The outer loops on the HA head seem to draw most of the antibodies, but in a given strain these loops can mutate to evade an antibody response within months," said Wilson. Antiviral drugs aimed at these and other viral targets also lose effectiveness as flu virus populations evolve.

"The major goal of this research has been to find and attack relatively unvarying and functionally important structures on flu viruses," said Damian Ekiert, a graduate student in the Scripps Research Kellogg School of Science and Technology who is working in the Wilson laboratory. Ekiert and Crucell's Vice President for Antibody Discovery Robert H. E. Friesen are co-first authors of the Science Express report.

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Read more: http://www.nctimes.com/blogsnew/bus...8c5-11e0-8048-001cc4c002e0.html#ixzz1RRgjPWAy

 

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Re: Antibody Discovery AdvancesUniversal Flu Vaccine Goal

Re: Antibody Discovery AdvancesUniversal Flu Vaccine Goal

A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

Published Online 7 July 2011
< Science Express Index
Science DOI: 10.1126/science.1204839

Research Article

A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

Damian C. Ekiert1,*,
Robert H. E. Friesen2,*,
Gira Bhabha1,
Ted Kwaks2,
Mandy Jongeneelen2,
Wenli Yu1,
Carla Ophorst2,
Freek Cox2,
Hans J.W.M. Korse2,
Boerries Brandenburg2,
Ronald Vogels2,
Just P.J. Brakenhoff2,
Ronald Kompier2,?,
Martin H. Koldijk2,
Lisette A.H.M. Cornelissen3,
Leo L. M. Poon4,
Malik Peiris4,
Wouter Koudstaal2,?,
Ian A. Wilson1,5,?,
Jaap Goudsmit2

+ Author Affiliations

1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2Crucell Holland BV, Archimedesweg 4-6, 2301 CA Leiden, The Netherlands.
3Central Veterinary Institute, Wageningen University, Lelystad, the Netherlands.
4Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
5The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

+ Author Notes

↵? Present address: FluConsult, Noordwijk, the Netherlands

?To whom correspondence should be addressed. E-mail: wilson@scripps.edu (I.A.W.); wouter.koudstaal@crucell.com (W.K.)

↵* These authors contributed equally to this work

Abstract

Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the VH1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.

Received for publication 25 February 2011.
Accepted for publication 10 June 2011.


http://www.sciencemag.org/content/early/2011/07/06/science.1204839.abstract