'Universal flu vaccine' a step closer

The Daily Telegraph has reported that scientists are a “step closer” to a universal flu vaccine following the discovery of a “super antibody” in a patient’s blood.

The news is based on a laboratory study that looked at finding ways to develop vaccines that offer broad protection against several flu strains. In the study, researchers isolated a human antibody that could target elements of flu virus particles shared between numerous strains. This antibody could in theory allow the body’s immune system to quickly detect and neutralise a range of flu infections. When tested in mice and ferrets, the antibody was found to protect the animals against various strains of flu that would normally prove fatal in the quantities used.

The flu vaccines currently available are only able to offer protection against selected strains, and seasonal vaccines have to be re-formulated each year based on the flu strains predicted to be in circulation. A universal flu vaccine would mean that a new seasonal flu vaccine would not have to be made each year, and one vaccination might last a lifetime. The antibody identified in this study could help researchers to develop such a universal vaccine, but tests in humans will be needed before we know whether this is the case.

Where did the story come from?

The study was carried out by researchers from the Institute for Research in Biomedicine in Switzerland and other research centres and biotechnology companies in Europe. It was funded by the European Research Council, the Swiss National Science Foundation, the Human Frontier Science Program, the UK Medical Research Council and the Wellcome Trust. It was published in the peer-reviewed journal Science.

This study was covered by a wide range of media sources, which generally covered it well. Some publications have highlighted that many research groups are currently working towards the goal of a universal vaccine. It should be noted that this particular study looked at sourcing antibodies against the influenza A form of the virus and not influenzas B or C.

Although influenza A is the most common flu strain, influenzas B and C still cause a significant proportion of flu cases. Therefore, as the antibody discovered has not yet been tested against these strains, this vaccine may not be effective against “all” flu strains, as suggested by the Daily Mail .

What kind of research was this?

This was laboratory and animal research that aimed to isolate and test antibodies that would be active against a wide range of flu viruses.

Antibodies are special proteins that the immune system uses to identify and fight threats such as viruses. When fighting viruses, antibodies work by binding to specific proteins found on the surface of virus particles, allowing the body to detect them and then fight them using the white blood cells. However, flu viruses are difficult for our immune systems and vaccines to combat as their genetic material can change rapidly, leading to changes in the proteins on their surface. These changes mean that a new, slightly different form of the virus may not be recognised by existing anti-flu virus antibodies. This research looked at finding antibodies that would bind to sections of protein that were common to several different flu strains, thereby potentially offering wider protection.

At present, a new seasonal flu 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 “universal” vaccine which can tackle all existing 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?

Influenza A viruses are the most common type of human flu virus, and have been responsible for human flu pandemics. Influenza A viruses fall into two groups, group 1 and group 2, and these groups contain 16 different strains of the virus. The authors report that thus far research has identified antibodies that can tackle either group 1 or group 2 viruses, but not antibodies that can recognise and target both groups. This research focused on identifying and testing such an antibody.

Haemagglutinin (HA) is a protein found on the surface of all flu viruses, and is the main target of anti-flu antibodies. However, different flu strains have slightly different forms of the HA protein, so these antibodies will often only recognise one strain and not others. The researchers wanted to identify an antibody which would identify all of the different forms of HA found on the surface of the 16 different group 1 and 2 flu viruses.

To do this, the researchers isolated over 100,000 antibody-producing cells from eight people who had been recently vaccinated against flu or who had recently had flu. They developed a method to screen large numbers of these cells to identify which ones produced antibodies which could recognise the different types of HA protein. For this screening they used the HA from whatever strain of flu virus had been used in the initial vaccination or was responsible for the person’s flu, as well as a different form of HA from a group 1 influenza A virus and a different form of HA from a group 2 influenza A virus. They needed to screen large numbers of antibody-producing cells because these “universal” antibodies may be very rare.

Once the researchers identified an antibody which could successfully bind to these sample group 1 and 2 HAs, they went on to determine the gene sequence the antibody-producing cell used to make this antibody, so that they could produce more of it in the lab. When they had more of the antibody, they tested whether it could bind to and neutralise a wider range of group 1 and 2 HA proteins. They also carried out experiments to look at the exact structure of the antibody, and to identify which part of the HA molecule the antibody binds to.

Finally, they tested whether injecting this antibody into mice and ferrets would protect the animals against flu viruses. They injected the mice or ferrets with the antibody, and then with a large dose of flu virus that would normally be lethal. They then looked at whether the antibody protected the animals from dying. They also looked at whether the antibody would work if injected after the flu virus injection.

What were the basic results?

Out of the 104,000 antibody-producing cells they tested, the researchers identified four cells from one donor which produced antibodies that successfully recognised the two different HA proteins present in the group 1 and 2 influenza A strains. The parts of these antibodies that bound to the HA proteins were found to be the same, and so the researchers then produced in the lab larger amounts of one particular antibody (called F16) carrying this same protein-binding region. The F16 antibody bound to and neutralised all of the group 1 and group 2 HAs tested. The researchers found that the antibody binds to a part of the HA protein which is highly similar (conserved) across all 16 group 1 and 2 flu virus strains.

In their animal experiments, the researchers used the F16 antibody and a slightly different version of this antibody called F16v3, which they thought might be more effective. Mice pre-injected with F16 or F16v3 did not die when injected with what would normally be a lethal dose of a group 1 flu virus (called A/Puerto Rico/8/34 [H1 N1]). An injection of F16v3 after the flu virus injection could also protect the mice against dying from a normally lethal dose of this group 1 virus or a group 2 flu virus. Pre-injecting ferrets with the F16 antibody also protected them against a normally lethal dose of a group 1 flu virus (called A/VietNam/1203/04 [H5N1]).

How did the researchers interpret the results?

The researchers concluded that they had identified an antibody that targeted and neutralised a broad spectrum of influenza A viruses. They suggest that this antibody could either be used as a vaccine itself, or to inform the development of flu vaccines.

Conclusion

This laboratory research has identified an antibody which can target group 1 and 2 influenza A viruses. This is reported to be the first time an antibody with this type of coverage has been identified; a property which may help researchers to develop a “universal flu vaccine” that can tackle a wide range of flu viruses. The antibody was then shown to protect mice and ferrets against group 1 and 2 flu viruses. Further testing will be required to test the antibody’s efficacy in humans.

While the antibody has been shown to be effective against influenza A strains tested thus far, there are also other, less common types of influenza virus that can infect humans: influenzas B and C. The antibody has not yet been tested against these strains. Therefore, the antibody identified does not provide truly universal flu coverage, which would need to offer protection against these other strains too.

Although most people recover from flu, it can be fatal in elderly people or people with compromised immune systems. 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 that mean that it is not recognised by existing anti-flu virus antibodies. Currently, a new vaccine has to be made each year to match the strains that are in circulation. Many researchers are working on developing a universal flu vaccine that can tackle all strains. This and similar studies may bring us closer to this goal.