Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

08.07.2011
An academic-industry collaboration by Scripps Research and Crucell finds broadly acting antibody against influenza viruses

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

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.

By sifting through the blood of people who had been immunized with flu vaccines, Goudsmit and his colleagues several years ago discovered an antibody that bound to one such vulnerable structure. In mice, an injection of the antibody, CR6261, could prevent or cure an otherwise-lethal infection by about half of flu viruses, including H1 viruses such as H1N1, strains of which caused deadly global pandemics in 1918 and 2009.

The Crucell researchers approached Wilson, whose structural biology lab has world-class expertise at characterizing antibodies and their viral targets. Ekiert, Wilson, and their colleagues soon determined the three-dimensional molecular structure of CR6261 and its binding site on HA, as they reported in Science in 2009. That binding site, or "epitope," turned out to be on HA's lower, less-accessible stalk portion. The binding of CR6261 to that region apparently interferes with flu viruses' ability to deliver their genetic material into host cells and start a new infection. That antibody is about to begin tests in human volunteers.

The Missing Piece

Crucell researchers subsequently searched for an antibody that could neutralize some or all of the remaining flu viruses unaffected by CR6261, and recently found one, CR8020, that fits this description. As the team now reports in the Science Express paper, CR8020 powerfully neutralizes a range of human-affecting flu viruses in lab-dish tests and in mice. The affected viruses include H3 and H7, two subtypes of great concern for human health that have already caused a pandemic (H3) or sporadic human infections (H7).

As with the CR6261 project, Ekiert and colleagues were able to grow crystals of the new antibody bound to an HA protein from a deadly strain of H3N2, and to use X-ray crystallography techniques to determine the antibody's structure and its precise epitope on the viral HA protein.

"It's even lower on the HA stalk than the CR6261 epitope; in fact it's closer to the viral envelope than any other influenza antibody epitope we've ever seen," said Ekiert.

Crucell is about to begin initial clinical trials of CR6261 in human volunteers, and the company expects eventually to begin similar trials of CR8020. If those trials succeed, aside from a vaccine the two antibodies could be combined and used in a "passive immunotherapy" approach. "This would mainly be useful as a fast-acting therapy against epidemic or pandemic influenza viruses," said Wilson. "The ultimate goal is an active vaccine that elicits a robust, long-term antibody response against those vulnerable epitopes; but developing that is going to be a challenging task."

Other authors of the paper, "A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses," are Gira Bhabha and Wenli Yu from Scripps Research; Ted Kwaks, Mandy Jongeneelen, Carla Ophorst, Freek Cox, Hans J.W.M. Korse, Boerries Brandenburg, Ronald Vogels, Just P.J. Brakenhoff, Ronald Kompier, Martin H. Koldijk and Wouter Koudstaal of Crucell Holland BV, Leiden, the Netherlands; Lisette A.H.M. Cornelissen of the Central Veterinary Institute, Wageningen University, Lelystad, the Netherlands; and Leo L. M. Poon and Malik Peiris of the Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong.

The research was supported by the US National Institute of Allergy and Infectious Diseases, National Institutes of Health; the US Department of Energy; and by Crucell Holland BV.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neuroscience, and vaccine development, as well as for its insights into autoimmune, cardiovascular, and infectious disease. Headquartered in La Jolla, California, the institute also includes a campus in Jupiter, Florida, where scientists focus on drug discovery and technology development in addition to basic biomedical science. Scripps Research currently employs about 3,000 scientists, staff, postdoctoral fellows, and graduate students on its two campuses. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, is ranked among the top ten such programs in the nation.

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>