Monday February 23 2009
The flu virus changes quickly, making it difficult to protect against
A “wonder jab to cure all flu” could soon be a reality according to a front-page story in the Daily Express. The newspaper says a “holy grail” flu vaccine is one step closer after scientists have found antibodies (disease-fighting cells) which target a weak spot on most forms of flu virus (including the deadly form of bird flu) and prevents them from infecting cells.
The American research in question is indeed exciting given the dangers of potential influenza outbreaks, which can be hard to control as the virus can mutate (change) into new strains. The study has discovered antibodies that are active against some severe forms of human influenza. Giving these to healthy people in the event of an outbreak could give scientists sufficient time to develop an appropriate vaccine.
However, the antibodies will need further research to determine whether they will be safe and effective in humans. Likewise, it will take more research to develop a safe vaccine that encourages the body to make these antibodies itself, rather than relying on the manufactured antibodies used in this study. Given the need for approaches to prevent and treat potential avian flu outbreaks, these areas will be keenly researched.
Where did the story come from?
This research was conducted by Dr Jianhua Sui and colleagues from Harvard Medical School, the Burnham Institute for Medical Research and the National Centre for Immunization and Respiratory Diseases. It was funded by the National Institutes of Health in the US, and published in the peer-reviewed medical journal, Nature Structural and Molecular Biology.
What kind of scientific study was this?
This was a laboratory study researching the ability of specific antibodies to neutralise a range of different strains of flu virus.
The influenza virus mutates rapidly into different strains, and each year the flu vaccine needs to be updated to match whatever strains of virus are circulating. Flu therefore poses a global threat to human health because of the possibility for pandemic flu, which occurs when a new viral strain emerges and infects a population with little or no immunity.
Scientists are seeking to develop a vaccine that provides strong protection across different strains of flu virus, and which might protect against a wide outbreak of avian flu (H5N1) should that ever happen. There have already been about 400 human cases of avian flu since 1997, with a 60% mortality rate in people with healthy immune systems. An outbreak of the flu could potentially kill thousands across the world.
In this laboratory study, researchers used genetic and biochemical techniques to select antibodies that could neutralise H5N1 infection both in mice and cell cultures outside living bodies. Influenza type A is the most common virus to infect humans, and in order to bind to host cells it uses two proteins on its surface: haemagluttinin and neuraminidase. The virus is further divided into varieties depending on which types of these two proteins it has on its surface.
Researchers infected insect cells with a particular type of H5N1 influenza virus. They used a technique called ‘antibody phage-display library’ to produce antibody-like molecules that were highly responsive to this virus. They isolated 10 unique antibodies, all of which were able to neutralise the viral subtype they started with. They then converted three of the antibodies into full-length human antibodies against the virus and tested whether these would protect mice against H5N1 flu infection, both when given as prevention before infection, and also when given as a treatment during infection.
Using molecular techniques the researchers investigated how the antibody was protecting mice. As many flu subtypes have similar chemical sequences in molecules on their surface, the researchers then examined how well the antibodies would bind with other viruses in cell cultures. They also looked at whether the antibodies would protect live mice from the H1N1 strain that caused the 1918 pandemic of Spanish flu.
What were the results of the study?
The researchers found that the antibodies they had manufactured protected mice from getting some types of flu infection, and reduced both viral replication in the lungs and viral spread to the spleen.
Further experiments revealed that the antibodies did not prevent initial binding of the virus to blood cells, but prevented the later step when the membranes of the two cells fuse. Complex biochemical investigations into the exact mechanism behind this prevention revealed that when the antibody binds to the virus it prevents the “large structural reorganisations required for membrane fusion”.
The manufactured antibodies bound to cells that were infected with several different viruses: three different H1 viral strains (including the H1N1 that caused the 1918 Spanish flu pandemic), an H2 virus, an H6 virus, H13 and H16, H9 from three different viral strains and one type of H11 virus.
The antibodies were found to protect mice from the H1N1 virus.
What interpretations did the researchers draw from these results?
The study manufactured antibodies that are active against certain flu virus types including those deriving from H5 types and all group 1 viruses (H2, H5, H1, H6, H13, H16, H11, H8, H12, H9) but not the group 2 viruses (H4, H14, H3, H15, H7, H10).
The researchers say that they have found that the antibodies target a region of the haemagluttinin molecule on the surface of the virus that is similar across a number of different types of virus, including the H1N1 (Spanish flu) and H5N1 (avian flu) strains. They say that because this region of the molecule does not mutate very much there is potential here for development of vaccines using these antibodies.
What does the NHS Knowledge Service make of this study?
This laboratory study will be of great interest to scientists, medics and public health professionals involved in planning for potential influenza outbreaks.
The researchers have made an important discovery in finding three antibodies that are active against types of influenza that have caused serious disease. These types include H1N1, the Spanish flu that spread pandemically in 1918 resulting in at least 20 million deaths worldwide and avian flu (H5N1), which can infect humans and is of concern to health professionals in case it mutates to a more transmissible form.
The Daily Express’ front-page coverage of this research may be misleading. This research does not represent a cure, and these antibodies only prevent infection by conferring on people a passive immunity. This means transferring ready-made antibodies to people before they are infected, or sometimes to treat them when they are already infected.
Passive immunity does not last long, and is different to vaccination, where the body is encouraged to produce its own antibodies in response to weakened viral material. Antibody therapy will probably be used to treat people in the event of an outbreak, but it will not give them long-term or lifelong protection.
While certainly of great interest and importance, this is early research in that the experiments involve cell cultures and mice, and it will be some time before we see the application of this to the prevention of flu in humans. However, given the importance of developing treatments for the flu this further research may not be far off.