Dirty, rotten swine flu – and how to beat it
Box 4 | New flu vaccines
The ‘egg’ method of vaccine production has worked for more than 50 years. But with a global population of well over six billion people, and growing, the task of producing enough vaccine to protect everyone against the constantly evolving flu virus is daunting – and also a significant cost for health authorities. Moreover, when a deadly form of the virus arises, a turn-around of several months to produce a new vaccine could cost millions of lives. The challenge, therefore, is to develop techniques to produce effective vaccines more rapidly and at a lower cost. Also, because influenza viruses are constantly changing by mutation, and new strains from birds and animals can establish themselves in the human population, scientists are also searching for the ‘holy grail’ of flu research: a single ‘universal’ vaccine capable of warding off all strains of the virus. Several approaches towards these objectives are being tested.
Live attenuated vaccine
Traditionally, the flu vaccine has contained a killed version of the virus (or parts of it). The advantage of killing the virus is that there is no risk that the vaccine will cause the disease when administered; the disadvantage is that the killed-virus vaccine can result in a weak response from the body’s immune system.
Recently, a nasally delivered, live attenuated (weakened) flu vaccine has been produced and is now in use in the United States. Live attenuated vaccines have a significant advantage over killed vaccines because – although they are weakened – they induce an immune response as if they were genuinely infectious pathogens. The live vaccine is able to reproduce to a limited extent in the body, increasing the efficiency of delivery and, often, helping to maintain immunity over time. Live attenuated vaccines stimulate the production of antibodies in a similar way to killed vaccines. But, unlike killed vaccines, they may also stimulate cell-mediated immunity and immunity at the site of infection, in the case of influenza in the respiratory tract. A potential risk with the use of live virus vaccines is the possibility that they might revert to a dangerous form, however, in most cases this is very remote. While they have been very successful for many diseases, technical problems such as stability have delayed their introduction for influenza.
Cell culture
Vaccine virus can be grown in cell cultures, eliminating the need for hens’ eggs. The advantages of cell culture include a reduction in manufacturing time, the elimination of potential allergic reactions to egg components, and the ability to rapidly ‘scale up’ production in the face of a pandemic. The use of a ‘closed’ system is also less prone to bacterial contamination than eggs and protects the operators from the viruses. Cell culture techniques can also be used in combination with genetically-engineered virus antigens to speed up the development of new vaccines. This was demonstrated recently at the University of Queensland, using a US patented procedure, to develop a swine flu vaccine in just a few weeks.
Reverse genetics
Reverse genetics involves the use of extracted flu virus genetic material to quickly create reassortant vaccine strains without handling dangerous viruses. In some cases this has already replaced the process of culturing new viruses together with a donor strain, and the sometimes laborious process of selecting a vaccine reassortant with the correct characteristics.
Adjuvants
On their own, existing non-living vaccines stimulate primarily the production of antibodies. To increase their effectiveness, an adjuvant can be added to trigger an innate immune response. This aids in the generation of more robust immunity including cell-mediated responses. Adjuvants include aluminium salts, oil-in-water emulsions and some materials with detergent activity; the search is on for others that are even more effective.
Universal vaccine
Existing flu vaccines target the antigens haemagglutinin and neuraminidase on the surface of the virus. These antigenic proteins are constantly changing, meaning that the scientists must continually adapt the vaccines to ensure they remain effective. Some flu proteins, on the other hand, are called ‘conserved’ proteins because they are common to all strains of the virus, and they rarely change. A vaccine that could effectively target a conserved protein might theoretically provide protection against all types of flu, including the swine and avian varieties. Many scientists searching for a universal flu vaccine are focusing on M2, a conserved protein that protrudes from the surface of flu viruses. Others hope to overcome the problems of the constantly changing surface antigens, by targeting a region within the haemagglutinin molecule that is conserved.
Several groups, including Australia’s John Curtin School of Medical Research, have developed candidate universal vaccines and some are being tested in human safety trials.
Boxes
Box 1. What is swine flu?
Box 2. Antiviral drugs for treating the flu
Box 3. How vaccines work
Related sites
Universal flu vaccine (Catalyst, Australian Broadcasting Corporation, 2 July 2009,)
New swine flu vaccine developed (News in Science, Australian Broadcasting Corporation, 29 June 2009) Egg beaters (Scientific American, 23 February 2004)
Boosting vaccine power (Scientific American, October 2009, pages 52-59)
Vaccine manufacturing: Challenges and solutions (Nature Biotechnology, 8 November 2006)
A long search for a universal flu vaccine (New York Times, 18 May 2009)
External sites are not endorsed by the Australian Academy of Science.
Posted February 2010.