First results from vaccine trial

A study published in the New England Journal of Medicine has described early tests of a swine flu vaccine in Australia. The results suggest that a single dose of the vaccine may be enough to produce an immune response, and that the vaccine appears to be safe in the short term with mostly mild to moderate side effects.

These findings are encouraging. This early research indicates that a single dose of this vaccine should prepare the body to fight off the virus but it does not show how effective the vaccine is in preventing swine flu or its longer-term safety.

It was also tested in healthy adults under 66 years of age so the results may differ in less healthy populations and in children and older populations. Once the swine flu vaccines are licensed for use, monitoring will continue to detect the possibility of serious but rare side effects, such as Guillain–Barré syndrome.

The study also found an unexpectedly high proportion of people who had not been vaccinated but who already had an antibody response to swine flu (over 30%, or 72 out of 240 participants). The researchers say that in older participants, this could be related to exposure to H1N1 viruses circulating in the 1950s, but as similar proportions of younger people also had immunity, there could be another explanation.

For example, it is possible the participants had already been exposed to swine flu. However, efforts were made to ensure this had not happened.

Alternatively, the immunity to swine flu could be an effect of the 2009 seasonal flu vaccine, as participants were more likely to show an immune response if they had also had this vaccination.

Where did the story come from?

This research was carried out by Dr Michael E Greenberg and colleagues from CSL Biotherapies, a company producing the swine flu vaccine in Australia. The study was supported by CSL with funding from the Australian government's Department of Health and Aging. It was published in the peer-reviewed New England Journal of Medicine .

What kind of scientific study was this?

This was a double-blind randomised controlled trial  that tested the safety of a swine flu vaccine and its ability to provoke an immune response.

The vaccine was produced in Australia using one of the strains recommended by the World Health Organization (WHO) for producing swine flu vaccine. The vaccine was prepared in hens’ eggs using the same techniques that are used to produce seasonal flu vaccines.

The researchers recruited 240 adults at one site in Australia, half of whom were younger than 50 and the other half 50 and over. Pregnant women were not eligible to participate. These participants were randomly assigned to receive a single dose of either 15 or 30 micrograms of the swine flu vaccine by injection. Neither the participants nor the researchers assessing their response knew which dose of vaccine had been received.

Blood samples were taken before the injection and 21 days afterwards. These were used to test how much antibody response against the swine flu virus the participants had before and after vaccination. A successful immune response was considered to be a specified level of antibodies against the virus (antibody titres 1:40). The researchers also looked at how many participants had increased antibody response to the virus after vaccination, even if it did not reach the pre-specified level for success.

The researchers asked the participants to record any side effects during the week after vaccination. They collected information about side effects of special interest, including nervous system problems such as Guillain-Barré syndrome (a disorder that can lead to numbness and paralysis of the legs and may progress to the body and arms), immune system disorders and other disorders. Any of these events or other serious adverse events during the 21-day follow-up were to be reported within 24 hours of experiencing them. If participants had flu-like symptoms, nose and throat swabs were taken to test for swine flu.

What were the results of the study?

Before vaccination, 31.7% of participants already had the pre-specified level of successful immune response against the swine flu virus. Participants were more likely to show this response if they had received the 2009 seasonal flu vaccination.

By 21 days after the vaccination, 96.7% of participants who had the lower dose of the vaccine, and 93.3% of participants who had the higher dose, showed a successful immune response against the swine flu virus. There was a significant increase in antibody response in 74.2% of participants, with a similar response from both doses.

Among people with the lowest levels of immune response to the virus before vaccination, over 86% had a significant increase in immune response. Of those who had higher levels of immune response to the virus before vaccination, over 60% had a significant increase in their immune response.

Nearly all side effects were of mild to moderate severity. Just under half (46.3%) of the participants had tenderness or pain at the injection site, and a similar proportion (45%) had general body symptoms such as headache and muscle pain. Two participants reported severe side effects. One person had vaccine-related muscle pain, malaise, and nausea that went away after five days with standard treatment. The other person had nausea that was judged to not be vaccine-related six to 10 days after the vaccination.

There were no adverse effects of special interest, serious adverse events or deaths among the participants.

Three people had flu-like symptoms and one of these people was found to have swine flu.

What interpretations did the researchers draw from these results?

The researchers concluded that a single dose of 15 micrograms of the swine flu vaccine produced a robust immune response, even though it was initially thought that two doses would be required. The researchers say these results will help to inform pandemic planning, especially as they say there is concern that low manufacturing yields may mean that there may not be enough vaccine.

What does the NHS Knowledge Service make of this study?

This study reports on the early testing of the swine flu vaccine produced in Australia. The results suggest that a single dose of this vaccine may be enough to produce an immune response and that the vaccine seems reasonably safe in the short term. There are a number of points to note:

• This study was of a swine flu vaccine produced in Australia that is unlikely to be the one used in the UK. The vaccine for the UK will undergo similar testing.
• There is the possibility that the levels of immunity seen were due to the participants being exposed to the swine flu virus itself rather than the vaccine. The researchers suggest that this is unlikely, as only one person in the study experienced flu-like symptoms and tested positive for the swine flu virus.
• The researchers say that the proportion of people with antibody response to swine flu at the start of the study was higher than expected. They say that among older participants, this could be related to exposure to H1N1 viruses circulating in the 1950s, but similar proportions of younger participants also showed immunity, suggesting that this is not the case. The researchers suggest that the immunity may be related to previous swine flu exposure (even though they tried to exclude people who may have been exposed) or to some effectiveness of the 2009 seasonal flu vaccine against swine flu.
• The authors note that to detect the possibility of serious rare side effects, such as Guillain–Barré syndrome, monitoring of people receiving the vaccine will need to continue after the swine flu vaccines are licensed for use.
• The study only looked at safety and immune response for 21 days after vaccination. Further monitoring will determine what the long-term effects of vaccination are in terms of its ability to prevent swine flu infection and safety.
• This study only included healthy adults under 66 years of age, and results may differ in less healthy populations, and in children and older populations.