Hunt for universal flu vaccine
“A single flu jab that kills off any strain of the virus for decades will soon be a reality,” reported the Daily Express.
The news story is based on early research in animals, testing ‘plasmid vaccines’ aimed at immunising the body against multiple strains of the H1N1 flu virus. The researchers found that when given in combination with a seasonal booster vaccine, the plasmid vaccines protected against numerous H1N1 strains. When combined with the adenovirus 5 booster, they also gave protection against other viral strains as well.
These findings are promising, and it looks as though this method may produce wider protection than existing vaccination methods. However, this research is in the early stages and has not yet progressed beyond the laboratory. It seems likely that this approach will be tested in humans at some stage, but when this may happen is unknown. The newspaper reports are premature in saying the vaccine confers protection against ‘every strain’.
Where did the story come from?
The study was carried out by researchers from the National Institutes of Health in Maryland and the Centers for Disease and Control Prevention, Atlanta, Georgia, US. The study was funded by the Vaccine Research Center, NIAID, and National Institutes of Health. The study was published in the peer-reviewed journal Science .
The news stories are premature in their claims about this scientific research, which will need a lot more testing to see whether a vaccine could be developed for potential use in humans.
What kind of research was this?
This laboratory and animal study is part of ongoing research looking into developing a ‘universal vaccine’ to protect humans against different influenza strains. The researchers say the 2009 H1N1 pandemic (swine flu) highlighted the need for such a vaccine.
When people become infected with a flu virus, their bodies produce antibodies against it. Antibodies are proteins that recognise and fight off invading germs, such as viruses. These antibodies will then remember this flu virus and fight it if it invades the body again.
Normally a person has immune protection against a flu virus if they have antibodies that target haemagglutinin (HA), which is a protein found on the surface of the influenza virus. HA is the protein that allows the virus to bind to and infect the body’s normal cells. Therefore, an antibody that binds to this would block or neutralise this virus.
The difficulty with viruses is that new strains of the virus with different HA molecules develop, which are then able to resist these antibodies. The idea behind a universal vaccine would be one that delivered ‘broadly neutralising antibodies’ that targeted a particular part of the HA protein (the ‘stem’), which does not vary across different strains. So far it has not been possible to develop such a vaccine.
This research investigated this possibility using something called ‘gene-based priming’, a technique that could, in theory, give an enhanced immune response to a vaccine, and cause the individual to start generating these broadly neutralising antibodies.
Gene-priming vaccines contain a circular piece of bacterial DNA (called a plasmid) into which the HA gene has been inserted. Once the vaccine has been injected into the body, cells could take up this DNA and start to produce the HA protein and display it on their surfaces. The body should then start to produce antibodies against this viral protein, hence giving protection against any invading influenza viruses displaying the same protein.
What did the research involve?
In this experiment, plasmids were created that encoded the haemagglutinin either from a H1N1 influenza virus or from a H3N2 influenza virus. The researchers injected mice with the HA-encoding plasmid at weeks zero, three and six. At week nine, the mice were injected with a booster – either the 2006-07 seasonal vaccine (targeting one H1N1 strain and one H3N2 strain), or an attenuated (‘safe’ non-replicating) virus (adenovirus 5) which also carried the gene for HA. They then tested whether the antibodies the mice produced in response to these injections could neutralise other H1N1 and H3N2 strains, and other viral strains.
This experiment was then replicated in other mice that were exposed to the strain of the H1N1 virus circulating in 1934. These mice were immunised with either an empty (control) plasmid, the HA-encoded plasmid, the seasonal vaccine alone, or with the encoded plasmid and booster combination.
Parts of these experiments were then repeated in ferrets and in monkeys.
What were the basic results?
The researchers found that the H1N1 plasmid vaccine combined with the seasonal booster gave an antibody response that could neutralise different strains of H1N1 dating back to 1934 and to a strain of flu from 2007. Priming with H3N2 plus the seasonal booster gave immunity against different H3N2 strains, but did not give any more protection against H1N1 than the seasonal booster alone.
The H1N1 plasmid and adenovirus 5 combination gave wider protection against strains other than H1N1, as the antibodies could also neutralise H2N2 and H5N1 strains.
In mice exposed to H1N1, those given the plasmid and seasonal vaccine combination had better survival than those given the plasmid alone, seasonal vaccine alone or the control plasmid. There was no significant difference in survival between the plasmid and seasonal vaccine booster and the plasmid and adenovirus 5 booster.
Similar results were seen in ferrets, confirming that the plasmid and adenovirus 5 booster combination protects against more diverse H1N1 strains. H1N1 plasmid and booster vaccination in monkeys also produced antibodies that could neutralise different H1N1 strains.
The researchers say these results show that the antibodies produced in response to the vaccination in mice, ferrets and monkeys did indeed recognise the ‘stem’ part of the haemagglutinin molecule.
How did the researchers interpret the results?
The researchers conclude that the vaccine resulted in the development of broadly neutralising antibodies that were effective against a number of H1N1 strains. As such, they say this research ‘provides a basis for development of a universal influenza vaccine for humans’.
Conclusion
This is complex and valuable scientific research. It found that H1N1 and H3N2 plasmid vaccines in combination with the seasonal booster, gave protection against numerous H1N1 and H3N2 strains. When the H1N1 plasmid was combined with the adenovirus 5 booster, protection was given against other viral strains as well (H5N1 and H2N2 strains).
The research is in the early stages and has so far been carried out only in animal models. The newsreports of a vaccine that protects against ‘every strain’ are premature. The current experiments have not tested whether the vaccine can produce effective antibodies against every strain of influenza virus that has ever circulated.
As influenza vaccines are constantly changing, the effects on these newer strains also cannot be predicted. However, it does look as though this method could produce wider protection than existing vaccination methods. As such, the findings are promising, and it seems likely that this approach will be tested in humans in future.
