More work towards universal flu vaccine

“Scientists have hailed a breakthrough in the search for a universal flu vaccine,” The Daily Telegraph has reported. The newspaper says that such a vaccine would save lives and money by eliminating the need for the annual jab.

The news is based on laboratory research which has identified an antibody that can target a family of flu viruses known as group 2 influenzas. Antibodies are special proteins that the immune system uses to identify and attack threats such as viruses. Testing the antibody in mice showed that it was able to protect against potentially lethal doses of two sample group 2 flu viruses.

Researchers had previously identified another, complementary, set of antibodies that target group 1 flu viruses. Therefore these antibodies could potentially offer the possibility of broad protection against group 1 and 2 flu viruses by combining the two in a single vaccine.

However, further testing will be required to test the effectiveness of these antibodies in humans. Although flu is relatively harmless to most of us, it can prove fatal to elderly people and people with compromised immune systems. A universal flu vaccine that can tackle all strains is being eagerly pursued by many groups of researchers, and the current study may bring us closer to this goal.

Where did the story come from?

The study was carried out by researchers from The Scripps Research Institute in the US and other research centres in The Netherlands, Hong Kong and China. It was funded by a number of international research bodies, including the US National Institute of Allergy and Infectious Diseases, National Institutes of Health and Department of Health and Human Services. The study was published in the peer-reviewed journal, Science Express.

The Daily Telegraph and Daily Express covered this story. The Telegraph did not explicitly report that the current study was in mice, but it otherwise provided good coverage and put the research into context. The Express reported that the antibody identified is active against all strains of flu, which is not correct – it is only active against group 2 flu viruses, although it could potentially be used in conjunction with an antibody that targets group 1 viruses.

What kind of research was this?

This was a laboratory and animal study that looked at human antibodies against flu viruses. The researchers say that in their previous research they had identified antibodies that were able to neutralise all of the strains of one group of influenza viruses called influenza A group 1 viruses, but not group 2 viruses. They wanted to see if they could identify an antibody that would neutralise all influenza A group 2 viruses.

They say that influenza A viruses that have caused human pandemics have come from both group 1 and group 2, as have animal flu viruses, which have crossed over into humans. For example, the 2009-2010 swine flu pandemic was caused by a group 1 influenza A virus. While there are also influenza B and C viruses, influenza A is the most common and the most dangerous form to humans.

The body’s immune system uses special proteins called antibodies to recognise and fight harmful microorganisms, such as viruses and bacteria. These antibodies work by attaching themselves to molecules such as proteins found on the surface of these microorganisms, allowing white blood cells to identify and attack them. Often we become immune to a particular infection if we have been exposed to it before, as the immune system “remembers” the molecules and can rapidly produce the appropriate antibodies to target them if exposed to them again.

Flu viruses are difficult to combat as their genetic material can change rapidly, leading to changes in the proteins on the surface of the virus and thereby preventing a person’s existing anti-flu antibodies from recognising them. There are also different strains of flu virus, and antibodies usually combat one or a few strains but not others.

At present, a new vaccine has to be made each year to match the strains that are in circulation. Researchers hope that they may one day be able to develop a vaccine that can tackle all flu virus strains and any new strains that arise by targeting the areas of proteins on the surface of the virus that do not change as readily.

This type of laboratory research aims to identify antibodies that are able to recognise a wide range of flu strains, as these may be useful in developing a “universal” flu vaccine.

What did the research involve?

The researchers used standard methods to isolate antibody-producing cells from people who had been recently vaccinated against flu. All flu viruses carry some form of a protein called haemagglutinin (HA) on their surface, but different strains have slightly different forms of the protein. In this research they specifically isolated cells that were producing antibodies against a particular form of haemagglutinin called H3, which is found on the surface of group 2 flu viruses.

The researchers then took the antibodies produced by these cells and tested them to see if they recognised other forms of HA found on other group 2 flu viruses. Antibodies against group 2 viruses were specifically being explored as previous research had identified antibodies that were active against a wide range of group 1 viruses: it was hoped that using the two in combination could provide a vaccine with wide coverage against most flu viruses.

Once they identified an antibody that could successfully bind to a wide variety of group 2 HA proteins, they tested whether injecting mice with this antibody would protect them against group 2 flu viruses. After they had given the mice the antibody, they injected them with a large dose of flu virus that would normally be lethal. They then looked at whether the antibody protected the mice from dying. They also looked at whether the antibody would work if administered after the flu virus injection.

Finally, the researchers carried out experiments to look at the exact structure of the antibody they identified, and to identify which part of the HA molecule the antibody binds to.

What were the basic results?

The researchers were able to isolate an antibody that they called CR8020, which bound to a wide variety of group 2 flu virus haemagglutinins (HAs), including different forms of the H3 viral protein that had been collected over 50 years, as well as other group 2 HA proteins called H7 and H10.

Mice pre-injected with CR8020 were resistant to two different group 2 flu viruses: they did not develop symptoms of flu or die. An injection of CR8020 two to three days after the flu virus injection could also protect the mice against dying from these viruses, although they did develop some symptoms.

The researchers found that the CR8020 antibody binds to a part of the HA molecule that is the same or very similar in all group 2 flu virus HAs tested thus far, thereby suggesting it could have a wide application against group 2 flu viruses.

How did the researchers interpret the results?

The researchers concluded that a mixture of antibodies targeting group 1 flu viruses (which they identified in previous research) and the CR8020 antibody that targets group 2 viruses “may be sufficient to neutralise most influenza A subtypes and, hence, enable development of a universal flu vaccine” or may provide a suitable antibody treatment for flu infection.

Conclusion

This experimental laboratory research has identified an antibody that can target one group of flu viruses (group 2). This complements another set of antibodies identified in previous research, which target group 1 flu viruses. Although this antibody has been shown to protect mice against two sample group 2 flu viruses, further testing will be required to test its efficacy in humans. The newspapers report that human trials of the anti-group 1 antibody are due to start soon, and human trials of CR8020 are being planned.

Although flu is relatively harmless to most of us, it can be fatal to elderly people or people with compromised immune systems. Flu viruses are difficult to combat as their genetic material can change rapidly. This leads to changes in the proteins on the surface of the virus, which means that they are not recognised by existing anti-flu virus antibodies.

As it is not yet possible to provide a universal vaccine, the current method for formulating each year’s seasonal flu vaccine looks at the range of flu viruses that are likely to circulate, and is intended to offer a broad range of protection against that season’s viruses. Seasonal flu vaccination is currently offered to at-risk groups, such as the elderly.

A universal flu vaccine that can tackle all strains is being eagerly pursued by researchers. The current study may bring us closer to this goal.