A new phase for flu vaccinations

It is the flu vaccination season – the time of year when millions of people are requested to receive potential protection against this virulent and potentially lifethreatening virus. Current vaccines are only effective in 30–40% of over 65-year-olds, as the immune system weakens with age. However, research is ongoing into a new national flu vaccine that could potentially protect more over 65s, and possibly save millions of lives, and billions in costs to the NHS.

The vaccine

The world’s first widespread human testing of a new flu vaccine began in September 2017. People aged 65 and over were asked to take part in a study that is supported by the National Institute for Health Research (NIHR) and was being delivered by the University of Oxford in Berkshire and Oxfordshire. Research into this vaccine has continued in Australia. Researchers believe the vaccine could have a significant impact on the global fight against the virus, which affects about a billion people worldwide every year, causing 250 000 to 500 000 deaths annually – mainly in the over-65 age group.

How it works

It is hoped that the vaccine will offer longer lasting and better protection than the currently recommended vaccines alone. This is because it uses a different mechanism to get the body to protect against the virus. Under the microscope, the flu virus looks like a spherical cushion with pin-like protuberances on its surface. The existing flu vaccines use proteins that lie on the outside of flu cells – the heads of the pins – to stimulate the body’s immune system to produce disease-fighting antibodies.

As the virus’s coat might change each year, so do the surface proteins, haemagglutinin and neuraminidase, meaning that the flu vaccine also needs to change. Scientists across the globe have to predict what each new annual strain of flu will look like. Unfortunately, by the time the vaccine has been made, the strain of virus that is causing illness has often changed, and the vaccine does not work as well. The new vaccine is different as it uses the core proteins of the virus – inside the ‘cushion’ – instead of the surface proteins.

These particular core proteins remain virtually unchanged in all influenza A viruses, providing researchers with the opportunity to create vaccines that will work against all of them. Crucially, the new vaccine stimulates the immune system to boost influenza-specific T-cells, instead of antibodies, that kill the virus as it tries to spread through the body. Everyone has some influenza-specific T-cells already, but the numbers of them are often too low to be protective. Previous research has found that these T-cells can help to fight more than one type of flu virus, and researchers believe this means that more people could be protected and the severity and duration of flu may be reduced.

The trial

Approximately 850 over-65s registered at six general practices took part in the UK contribution to the study, known as the Invictus trial, in Berkshire and Oxfordshire. Half of participants received the regular annual immunisation in combination with the new vaccine, which had successfully undergone initial safety testing, the regular immunisation and a placebo shot, so the two could be compared. The results of this aspect of the research are still being analysed, but findings were sufficiently encouraging to justify a larger study in Australia during the most recent southern hemisphere flu season.

The vaccine was developed by Oxford University’s Jenner Institute with Vaccitech, a spin-out company from the institute. The study was being sponsored by Vaccitech and implemented by the university’s Nuffield Department of Primary Care Health Sciences with support from the NIHR Clinical Research Network Thames Valley and South Midlands, a Department of Health-funded organisation that provides staffing to ensure research studies are run in the health service. Professor Sarah Gilbert, Professor of Vaccinology at the university and co-founder of Vaccitech, says:

‘Every year, flu in older adults causes serious illness and sometimes death. We want to improve the situation, but in order to do that we need volunteers to help us test a new vaccine.’ Chris Butler, principal investigator of the study, is Director of the Primary Care Clinical Trials Unit, University of Oxford, and a practicing GP in Mountain Ash, South Wales. He says there was ‘a huge response’ to the study, and that ‘many people gave generously of their time to support the research.’

Researchers recruited forward-thinking, research-minded practices in Oxfordshire to help with the study. Theyasked GPs to write to patients who might be eligible to take part in the trial, to explain the study and that patients who were interested in taking part should contact the Clinical Trials Unit. Appointments were then set up with GP surgeries to meet the study’s nursing staff, explain the study, confirm eligibility of patients, take informed consent and administer the vaccine.

Professor Butler says the GP and the practice staff involved in the trial ‘made a tremendous contribution.’ ‘As well as putting us in touch with patients and giving us the space to carry out vaccinations, the GP practices helped us with following up patients who were vaccinated as part of the study,’ he says. He adds that practice staff have been ‘key to making it all happen.

As somebody who does a lot of clinical trials in general practice, this was an amazing study. We were overwhelmed by the dedication of the research practices helping us implement it and the positive response from patients who came forward in large numbers wanting to help with our research.’ Professor Butler says that if this new approach to flu vaccinations works, ‘we could be talking about saving millions of people from the consequences of flu, and billions of pounds in savings for the NHS. ‘It would be a considerable step forward for healthcare if the vaccination works’, and the whole winter crisis associated with the NHS and flu ‘will look very different if we can offer better flu vaccines’, he says.

The implications of this new vaccination, is it is proven to be effective, ‘are massive, not only for the NHS but worldwide’, he believes. For Professor Butler, the study is a ‘win-win for general practice’, and those patients taking part. He believes this ground-breaking research ‘could transform care, save lives, prevent numerous hospital admissions, and serious illness’. He expresses his gratitude to the buy-in from GPs, practice managers, staff and patients who have volunteered to help: ‘It’s been heartwarming to see the public’s response to this research, and their eagerness to get involved and volunteer their time.

 

Author: Kathy Oxtoby