Clinical trials of newly developed vaccines for swine flu have begun in the USA and Australia. These human studies will gather data on the safety and effectiveness of the vaccine.
The National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health in the USA, announced yesterday that a network of medical research institutions is about to begin a series of clinical trials to gather safety and efficacy data about some of the new influenza vaccines.
- At the same time, two vaccine manufacturers in Australia (CSL and Vaxine) have also begun testing their vaccine in healthy adult volunteers.
- The clinical trials will provide important early safety and efficacy data about the vaccines. In particular, the researchers will be monitoring adverse effects and immunogenicity (how well the vaccine provokes an immune response). They will also be assessing the dose required to be effective and whether the vaccine can be given alongside seasonal influenza vaccination.
- The American trials will be in healthy adult volunteers and in elderly volunteers who are also receiving the seasonal vaccine. If early results are positive, further studies may begin in healthy adolescents and children.
- The trials may take some months to complete, and the vaccination programmes are likely to begin before the full results are available. However, there should be sufficient results by September or October to spot real safety concerns and to allow governments to begin planning for the use and distribution of the new vaccines. Safety will continue to be monitored through surveillance when vaccination programmes are introduced nationally.
What are the WHO’s current recommendations for vaccines?
At a special meeting of the Strategic Advisory Group of Experts (SAGE) on July 07 2009, the WHO considered the potential options for vaccine use. They came up with some recommendations that were endorsed by the WHO Director-General, including:
- Healthcare workers should be immunised first.
- For other groups it is suggested that countries should decide their own vaccination policies and priority orders depending on country-specific conditions, possibly commencing with pregnant women and anyone aged over six months with one of several chronic medical conditions, followed by healthy young adults between 15 and 49 years of age, healthy children, healthy adults aged 50 to 64 years and healthy adults aged 65 years and above.
- Post-marketing surveillance of the vaccine is very important, particularly in certain population groups. This is because some new technologies are involved in the production of these vaccines and these have not yet been fully tested in certain groups. It is also important that results of this surveillance are shared widely in the international community so that countries can make any necessary adjustments to their vaccination policies.
- The production of particular types of vaccine formulations was also promoted, including live attenuated viruses and those that have oil-in-water adjuvants, which would help to protect against drifted strains of the virus (slightly mutated versions of the virus).
How are vaccines made?
To make a vaccine, a large amount of the virus or bacteria is needed. In the case of swine flu, the US Centers for Disease Control and Prevention (CDC) began isolating and preparing strains of the swine flu virus as soon as the first human case became known. These strains were sent to its counterparts in other countries including the National Institute for Biological Standards and Control (NIBSC) in the UK. These organisations prepare the virus strains to be used in making the vaccine.
Viruses can be grown in hens’ eggs, but often the infectious influenza virus strains do not grow well in eggs. To get around this, the infectious virus is injected into the eggs with another influenza virus that thrives in eggs. The two viruses swap pieces of their genetic material and produce hybrids, some of which both grow well in hens’ eggs and also have the elements of the disease-causing virus needed for a vaccine. These hybrids are isolated and the best candidate for making a vaccine is selected. This chosen hybrid strain is then grown and distributed to vaccine manufacturers.
The vaccine manufacturers use dead or weakened virus to create the vaccine. Other constituents can also be added to the vaccine, such as a suspending fluid to carry the virus into the body, preservatives and stabilisers that allow the vaccine to be stored safely, and chemicals to help the vaccine to promote an immune response.
When will a vaccine be available?
Vaccine development usually takes about six months and it began in April 2009. The WHO suggests that the first doses of influenza A H1N1 vaccine are expected as early as September 2009. The UK government says that the first batches of vaccine are expected to arrive in the autumn, and 30m double doses (enough for half the population) are expected to be available by the end of the year. The government has ordered enough vaccine for the whole population, and when it becomes available will focus on those at the greatest risk first.
Who will be a priority for vaccination?
The administration of the vaccines will need to be prioritised. The decision on prioritisation of the population will be taken on the basis of which groups are being most affected by the virus, when the vaccine arrives and how best to protect the NHS from being over-stretched.
How effective and safe will the vaccine be?
Vaccination is very effective in preventing and reducing the impact of serious illness. Although vaccines are not 100% effective and can become less effective if the virus mutates, they still offer some protection. Current flu vaccines last for about a year and give about 70-80% protection against infection with strains of influenza virus that are very similar to those used to make the vaccine. It is too early to predict how the swine flu virus might mutate. The WHO is closely monitoring it for changes, and this will help countries to make a quick response if the virus undergoes important changes.
The human trials that are currently underway will provide some evidence of the short-term safety and effectiveness of the vaccines. In particular, the researchers will be monitoring side effects and also how effectively the vaccine prompts a response from the immune system (its immunogenicity). The vaccines will be approved for use by national authorities. In this country the Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for monitoring the safety of flu medicines and vaccines. Safety monitoring will be ongoing once the vaccine programme is introduced.