Dirty, rotten swine flu – and how to beat it
Key text
This topic is sponsored by CSL Limited.
A potentially dangerous new flu has arrived, closely pursued by a new vaccine
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You will get more from this topic if you have mastered the basics of the immune system – these links will take you to an annotated list of sites with helpful background information. |
Related publication: The Science of Immunisation: Questions and Answers
On 11 June 2009 the World Health Organisation (WHO) declared that the 2009 influenza A (H1N1) virus, better known as swine flu, had become a pandemic. A new virus was stalking the globe, with huge potential consequences for the world’s population.
Some people have called it a false alarm, but swine flu is not to be sneezed at (Box 1. What is swine flu?). It is new, which means that few people have immunity to it. It is also highly contagious; since it was first detected in April 2009 it has spread to nearly every country on the planet.
Click for an up-to-date map showing countries affected by swine flu.
So far the death rate seems to be comparable to ‘normal’ or seasonal flu; however, it is affecting younger people more and having less impact on older adults. By January 2010 there had been 12,799 officially confirmed deaths associated with swine flu worldwide (although this is only a small proportion of the total number). In Australia, there had been 37,562 confirmed cases of swine flu and 191 deaths. However, although health authorities don’t have the full picture yet, there are fears that the 2009 H1N1 virus will change into something more deadly. Since most people have low immunity to it, a more virulent form of the virus could be disastrous.
Provides information for consumers on the H1N1 vaccine developed in Australia.
(CSL Limited, Australia)
This has happened before. In 1918, when the world was just beginning to recover from the ravages of World War 1, an even more deadly enemy struck – the Spanish flu. This disease started quietly, like swine flu, but then mutated. Within two years an estimated 50 million people were dead from it, which was more than three times the number of people killed in the war.
But pandemic need not equate to pandemonium or panic. Today’s global travel might help diseases to spread with frightening speed, but our defences are better. Effective antiviral medicines, for example, are widely available today (Box 2: Antiviral drugs for treating the flu). Even more importantly, we have a much greater ability to develop vaccines to fight new viruses and to produce them on a large scale. In Australia, one company – CSL Limited – has already made an effective swine flu vaccine and manufactured millions of doses to be made available to all Australians.
The making of a vaccine
The ‘H’ in H1N1 stands for haemagglutinin and the ‘N’ stands for neuraminidase; both are proteins found on the surface of the influenza (flu) virus. They exist in many different forms and combinations across the different flu strains, and these are represented by numbers. For example, H1N1 is characteristic of a swine-related flu while H5N1 is a form of the avian (bird) flu.
Flu virus names like H1N1 and H5N1 come
from the different forms of the haemagglutinin
(H) and neuraminidase (N) proteins on their
surface. (Image: Centres for Disease Control
and
Prevention)
Vaccines work by stimulating the body’s immune system to produce antibodies which recognise antigens – molecules like the H and N proteins – on the surface of the microorganism (Box 3: How vaccines work). To do this, weakened or killed microorganisms – such as viruses – are injected into the body to introduce the antigens to the immune system. In the case of influenza most of the vaccines currently used – and all of those used in Australia – use killed viruses.
The most common technique for growing virus for a flu vaccine is more than 50 years old and can be traced to Sir Frank Macfarlane Burnet, one of Australia’s most distinguished scientists and winner of a Nobel Prize in Physiology or Medicine. In the 1930s, Macfarlane Burnet pioneered the use of hens’ eggs to grow and study viruses. These days the allantoic cavity of fertilised hens’ eggs is used to both create an initial ‘seed’ virus and to scale up production of the virus for the final vaccine.
In April 2009, when health authorities became aware that a virulent new strain of the flu virus had surfaced, a pre-planned process was initiated, led by the WHO. Scientists at the WHO Collaborating Centres for Influenza, isolated three representative strains of the new virus from patients in Mexico and California and sent samples to vaccine manufacturers.
At CSL, the first step in preparing the swine flu strains for vaccine manufacture was a process called ‘reassortment’, which normally takes around four weeks to complete. Most wild flu viruses reproduce poorly under laboratory conditions; reassortment is designed to mix the genes of the wild, virulent flu with those of a harmless ‘donor’ strain (in the case of the swine flu vaccine, an H3N2 vaccine strain). The aim is to produce a hybrid ‘seed’ virus that has the outer antigens of the swine flu virus – so that it will stimulate the production of antibodies in the person being vaccinated – and the inner characteristics and therefore multiplying ability of the high-yielding donor virus.
To produce a swine flu vaccine as quickly as possible, hens’ eggs were injected with the donor virus and one of the three swine flu strains and incubated for about two days. Flu viruses have eight strands of RNA; during incubation, the RNA from the two strains mix together with the potential to produce up to 256 combinations, called ‘reassortants’.
The next step was to select the best vaccine candidate from the reassortants. Those with the outer characteristics of the donor virus – and therefore of no use for the vaccine – were eliminated by adding antibodies that are effective against the H3N2 virus. From the remaining reassortants, the combinations that grew best were selected. These were tested to ensure that they had the outer characteristics of H1N1, and they were also injected into ferrets to test the immune response. The most successful reassortants from this process constituted the seed viruses for vaccine production.
A seed virus is made for flu vaccines by crossing the virulent form with a harmless flu strain.
(Image: National Institute of Allergy and Infectious Diseases, USA Government)
At the CSL laboratory, a series of tests was then conducted to find the optimal growth conditions for the seed virus. These were used to produce the vaccine as follows:
- Seed virus was injected into the allantoic cavities of hens’ eggs, and incubated for about two days to allow the virus to replicate. One egg produces enough virus for around one shot of the vaccine, so to make enough vaccine for every Australian requires many millions of eggs.
| - The viruses were extracted from the allantoic fluid of the eggs.
- The purified and concentrated viruses were killed using chemicals and treated with detergents to break the viruses into ‘subunit’ forms.
- The vaccine concentrate containing viral antigens was tested in clinical trials – using volunteers – to determine the amount needed to stimulate adequate immunity, and to ensure its safety.
- Individual doses were packaged into vials and syringes, which were sealed, inspected and labelled to show the vaccine batch, lot numbers, and expiry date.
This process of vaccine development and production although effective, has been described by some as old-fashioned and slow in the face of a highly virulent and contagious disease outbreak. Research is under way to develop faster, easier techniques. There is also hope that, eventually, a ‘universal’ flu vaccine will be developed (Box 4. New flu vaccines).
In Australia, the first flush of swine flu has passed, but further waves are expected. By the time it comes again it is hoped that most of the population will have been vaccinated, so will have developed immunity against the virus. Australians will hopefully be forearmed against, what could still turn out to be, a pig of a problem.
Boxes
1. What is swine flu?
2. Antiviral drugs for treating the flu
3. How vaccines work
4. New flu vaccines
Related Academy material
The Science of Immunisation: Questions and Answers
This publication aims to address confusion created by contradictory
information in the public domain. It sets out to explain the current
situation in immunisation science, including where there is scientific consensus and where uncertainties exist. The Science of Immunisation: Questions and Answers was prepared by a Working Group and Oversight Committee made up of
Academy Fellows and other Australian scientists with internationally
recognised expertise in immunology.
Nova
Immunisation – protecting our children from disease
Bird flu – the pandemic clock is ticking
Kissing the Epstein-Barr virus goodbye?
Cancer immunotherapy – redefining vaccines
Interviews with Australian Scientists
Professor Frank Fenner (Microbiology and virology)
Professor Ian Frazer (Immunology)
Professor Gordon Ada (Microbiology)
Sir Gustav Nossal (Immunology)
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Australian Academy of Science.
Posted February
2010, edited August 2012.