Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery points to a new path toward a universal flu vaccine

03.07.2015

By taking advantage of a previously unknown mechanism within the immune system, researchers think they may be able to improve the vaccine

Flu vaccines can be something of a shot in the dark. Not only must they be given yearly, there's no guarantee the strains against which they protect will be the ones circulating once the season arrives.


Antibodies bind to a flu virus protein (grey) with their variable regions (blue) forming an immune complex. The antibodies' Fc region (red) will bind to immune cells. Researchers think flu vaccines could be improved by including immune complexes that contain antibodies with modified Fc regions.

Credit: Laboratory of Molecular Genetics and Immunology at The Rockefeller University

New research by Rockefeller University scientists and their colleagues suggests it may be possible to harness a previously unknown mechanism within the immune system to create more effective and efficient vaccines against this ever-mutating virus.

"While the conventional flu vaccine protects only against specific strains, usually three of them, our experiments show that by including modified antibodies within the vaccine it may be possible to elicit broad protection against many strains simultaneously," says senior study author Jeffrey Ravetch, Theresa and Eugene M. Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology. "We believe these results may represent a preliminary step toward a universal flu vaccine, one that is effective against a broad range of the flu viruses."

In a paper published July 2 in Cell, the team describes a new strategy that revolves around antibodies, immune proteins that target specific foreign proteins, called antigens. One end of the antibody latches on to an antigen, the other end, called the Fc region, binds to immune cells and so helps coordinate the immune response.

It was already known that chemical modifications to antibodies' Fc region altered their interactions with immune cells, including B cells, which produce antibodies. In experiments that began with human volunteers, the team, led by Taia Wang, an instructor in clinical investigation, and Jad Maamary, a postdoc, both in Ravetch's lab, investigated how changes to this region might be used to bolster an immune response: namely the production of more potent antibodies against the flu virus.

Every year in the United States, influenza is implicated in the deaths of thousands of people, mostly 65 and older, and causes serious disease in many others. The virus makes for a difficult target for vaccines because its strains are so diverse, and new ones are constantly emerging. Types A and B cause seasonal flu epidemics. Influenza A viruses are further broken down into subtypes based in part on their surface proteins, which include hemagglutinin, the "H" in H1N1, for example. The subtypes are further divided into strains.

Currently, most flu vaccines in the United States are formulated to target a total of three or four viral strains: H1 and H3 influenza A viruses, plus influenza B virus strains. The strains are selected based on public health experts' predictions for the coming flu season. But sometimes they are wrong, rendering the shots ineffective. A universal flu vaccine has become something of a holy grail, and a number of strategies have been proposed to create it. Work in the Ravetch lab suggests a new alternative: chemical modifications to the Fc region of antibodies. These regions go on form complexes with vaccine antigens, which then modulate the evolving vaccine response.

First, the researchers vaccinated healthy volunteers with a seasonal flu vaccine containing an inactivated strain of the H1N1 virus. They then tracked the volunteers' immune responses via blood samples, keeping an eye out for chemical modifications to antibodies against the hemagglutinin protein.

About seven days after the vaccination, they saw a spike in sialylated antibodies, meaning sialic acid, an important signaling molecule, had been added at a specific spot on the Fc region. The greater the sialylation, the better a person's response to the vaccine.

To tease apart how this chemical modification improves the immune response, the researchers used cell cultures and mice to study the effects of sialylated Fc regions binding to B cells. Their experiments revealed a complex interaction that ultimately pushes the B cells to produce antibodies with a higher affinity to their antigens. It begins when a sialylated Fc region binds to a receptor protein known as CD23 on the B cells, prompting CD23 to activate a second receptor, FcγRIIB, which, in turn, discourages B cells producing low affinity antibodies. In this way, the sialylation on Fc regions establishes a high threshold for the immune response, so that only B cells producing the highest affinity antibodies are activated. The result of the higher affinity was broad protection against H1 subtype influenza viruses.

The researchers then used this knowledge to improve the vaccine itself. They modified the H1N1 vaccine so it contained not only protein from the virus itself, but also sialylated antibodies against that protein.

"When we immunized mice with just the H1 protein from one strain or with the sialylated complexes containing the same viral protein, we found both offered equal protection against the same strain of flu. However, when we exposed them to strains expressing different versions of the H1 protein, only the sialylated immunizations offered protection," Maamary says. "This was no small accomplishment, because H1 viruses can vary significantly from one another."

"The new mechanism we have uncovered, by which a vaccine containing sialylated antibodies elicits broadly protective antibodies, could potentially be harnessed to reduce the tremendous morbidity and mortality caused by seasonal influenza virus infections," Wang says. "We are now looking into applying this strategy toward improving existing vaccines; ideally, this would result in a vaccine that provides life long immunity against flu infections."

Wynne Parry | EurekAlert!

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>