Respiratory infections affect billions of people every year and are among the top five causes of death worldwide. Despite recent medical advances, viruses such as influenza and respiratory syncytial virus (RSV) can still cause severe and even fatal illness.
Milder infections, including the common cold, are usually not fatal. But the cold can be caused by many different viruses, and it leads to a lot of time off work and a heavy cost to the economy.
These infections hit some groups harder than others. People living in deprived areas, older people and very young children are more likely to become seriously ill or die.
A government-funded research project called Triumph-NK, based at the University of Southampton, aims to prevent that harm. Our team is working on a new kind of vaccine that could protect against a wide range of respiratory viruses and be used immediately in an outbreak or even a pandemic.
The project is part of a wider programme called “sustained viral resilience”. Its aim is to strengthen the body’s first line of defence, known as the innate immune system.
The immune system has two main parts: first responders (the innate system) and a second line of defence (the adaptive system). Current vaccines work through the adaptive system, which is precise but slow to get going, so a virus can keep spreading in the meantime.
Natural killers
These vaccines also have to be developed separately for each virus, which takes more time. The project hopes to get around both delays by targeting a type of immune cell called a natural killer cell.
Natural killer cells are among the first cells to respond to a viral infection. They recognise molecular flags on infected cells that signal danger, then destroy those cells, killing the viruses inside and stopping the infection from spreading through the body.
Cells and antibodies of the adaptive system are very precise, and usually recognise only one virus or even one strain of a virus. Natural killer cells can spot cells infected by a broad range of different viruses.
Until recently, scientists thought natural killer cells were short-lived. Over the past decade, research has shown that some can survive in the body for a long time.
These long-lived cells are known as memory natural killer cells. They respond faster to many different viruses, and they are found in the nose and lungs, where respiratory infections begin.
Triumph-NK aims to find new ways to program natural killer cells in the body to become memory natural killer cells. They would then act as gatekeepers for the nose and lungs, stopping viruses from entering the body.
The first step is to work out which type of memory natural killer cell is best suited to the job. Our team is studying natural killer cells in the nose and lungs using DNA and RNA sequencing, while also identifying the molecular flags on the surface of the lung natural killer cells.
Once these cells are clearly identified, we will test different ways of making them in the laboratory using a range of stimuli. When they find the right combination, we will design a vaccine to deliver those stimuli using the mRNA technology behind the COVID vaccines.
The vaccine will be tested in the lab against a broad range of viruses, including influenza, COVID and RSV. It will then need thorough testing before human studies, which we hope to begin within the next five years.
If the work succeeds, the result would be a cost-effective, off-the-shelf vaccine that protects against many different viruses. It could be given immediately to vulnerable groups, such as older people and people with weakened immune systems, to prevent severe respiratory infection.
The biggest test will be whether the approach can deliver the same broad protection in people that it shows in the laboratory. If it can, it could change how quickly we respond to new respiratory viruses, giving scientists more time to develop targeted vaccines while helping protect people from the earliest days of an outbreak.