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Essential Science: Developing a universal flu vaccine

A candidate for universal flu vaccine, designed to protect a person against multiple strains is being examined by researchers. In a new step, researchers from the University of Pennsylvania School of Medicine have developed a modified-RNA vaccine which elicits protective response in mice to a conserved region of the flu virus. This success with animals could lead to the commercialization of a similar all-protective vaccine for humans. Proof of concept for RNA vaccines have previously been demonstrated in humans and the prospects for further development into commercial products remain encouraging.

Structure of influenza virus

Structure of influenza virus
roche.com

Universal flu vaccine

A universal flu vaccine is flu vaccine that is effective against all influenza virus strains. This would be irrespective of the virus subtype or viral genetic drift. This means such a vaccine would not require modification from year to year. Currently there was is approved universal flu vaccine for general use. However, there are various vaccines in development at different research centres. The new study featured is the latest iteration in the quest for a universal vaccine.

An intricate pattern - a molecular model of the influenza virus. The influenza virion (as the infect...

An intricate pattern – a molecular model of the influenza virus. The influenza virion (as the infectious particle is called) is roughly spherical. It is an enveloped virus – that is, the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies.

In a typical year, the annual flu shot protects around 60 percent of vaccinated people. The aim of the universal vaccine would be to take this figure close to 100 percent. The major challenges are the need for clinical trials; regulatory hurdles; a multitude of technical challenges; and for production of such a vaccine to be profitable for pharmaceutical companies.

New vaccine

The candidate vaccine, from the trials, has elicited a strong antibody response to a portion of flu viruses. This is a surface structure termed the hemagglutinin stalk. The stalk is a glycoprotein and it is responsible for binding the virus to cells with sialic acid on the membranes, such as cells in the upper respiratory tract.

Hemagglutinin is also responsible for the fusion of the viral envelope with the endosome membrane, after the pH has been reduced. The name “hemagglutinin” comes from the protein’s ability to cause red blood cells (erythrocytes) to clump together (or “agglutinate”).

The challenge is that most antibody responses are directed against the outermost “head” region of the hemagglutinin protein. This protein generally mutates rapidly. Furthermore, strains of flu that common to one flu season are generally replaced by other strains with different hemagglutinin head structures in time for the next flu season.

The new vaccine instead uses mRNA molecules that encode hemagglutinin proteins to trigger an antibody response. When injected into a recipient, these RNAs are absorbed by immune system dendritic cells and then translated into copies of the hemagglutinin protein by the protein-producing machinery within these cells. This intra-cell production of viral proteins mimics a real flu infection and elicits a strongly protective antibody response. This target area does not vary from one flu subtype to another, offering the potential for cross-seasonal protection.

A nurse draws blood from a volunteer taking part in an Ebola vaccine trial at the Oxford Vaccine Gro...

A nurse draws blood from a volunteer taking part in an Ebola vaccine trial at the Oxford Vaccine Group Centre for Clinical Vaccinology and Tropical Medicine (CCVTM) on September 17, 2014
Steve Parsons, Pool/AFP

Trials of the vaccine successfully protected mice from infection by different flu virus strains. According to lead researcher Dr. Drew Weissman: “This vaccine was able to do something that most other candidate flu vaccines have not been able to do. It was able to elicit protective responses against a conserved region that offers broad protection.”

Research published

The new research has been published in the journal Nature Communications. The paper is titled “Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies.”

Essential Science

Bread  produced locally from a mill near Ware in Hertfordshire. Thick crusts and soft chewy dough in...

Bread, produced locally from a mill near Ware in Hertfordshire. Thick crusts and soft chewy dough inside.

This article is part of Digital Journal’s regular Essential Science columns. Each week Tim Sandle explores a topical and important scientific issue. Lat week we explored new research which has found that, contrary to some dietary advice such as the Atkins Diet, a moderate carbohydrate intake may be best for general health and well-being.

The week before we discussed the work of researchers from University of California San Diego, who managed to turn a powerful and viscous disinfectant into breathable mist for the first time. This development could help with the much-needed fight against hospital-acquired infections.

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Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, business, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.

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