‘Killer’ immune cells may lead to universal flu vaccine

Scientists have identified ‘killer’ immune cells that can fight all known strains of flu virus, a “game-changing result” that could lead to a universal, one-shot vaccine against the potentially deadly disease. These microscopic killers are white blood cells that can maintain a memory of previous exposure to a flu strain, said researchers from the University of Melbourne in Australia. If they recognise an invader, these cells start an immune response to target and kill off the virus — stopping the infection, they said. Despite hopes that the ‘memories’ of killer cells — formally known as CD8+T cells — could be used to create a vaccine that would last for life, previous studies have shown that these cells could only mount a repeated attack against strain A.

In a study published in the journal Nature Immunology, scientists revealed game-changing results — the ‘killer cells’ can actually fight all influenza strains, A, B and C. “Our team has been fascinated by the killer cells for a long time,” said Katherine Kedzierska, a professor at the University of Melbourne.

Working with Fudan University in China, the team studied the immune responses of patients to the first outbreak of the avian-derived H7N9 influenza virus (bird flu) in China in 2013. This outbreak was contracted directly from birds and was dominated by the type A virus. It hospitalised more than 90 per cent of infected people and killed more than 35 per cent of them. The research found that those patients who recovered within two to three weeks had robust killer CD8+T cell responses, whereas those who died had a diminished presence of the ‘killer’ cells. “So our next step was to discover how their protective mechanism worked, and if it had potential for a flu vaccine,” said Kedzierska. The flu virus is composed of protein coat that covers its genetic code in its core,” said University of Melbourne PhD candidate Marios Koutsakos. The team analysed which parts of the flu virus were common in strains A, B and C in order to find out which would be the best target for a universal vaccine. When infected, our cells dissect the flu virus and use a protein called HLA to present parts of the virus (peptides) on the cell surface, alerting the immune system that they have been compromised. This HLA and viral peptide combination act as a passport or a unique identifier, known as an epitope.

‘Killer’ cells recognise it, triggering them to kill off the infected cell.

The researchers focused on which epitopes were common among all three flu strains. “We started with 67,000 viral sequences to look for epitopes common among all the flu viruses. These tens of thousands were eventually narrowed down to three epitopes that were cross-reactive, that is they are common to all flu viruses,” Koutsakos said. “We identified the parts of the virus that are shared across all flu strains, and sub-strains capable of infecting humans,” he said. Having established which sections of the virus were conserved or cross-reactive, the researchers then conducted tests to establish if those viral parts did produce a robust immune response.

These flu virus epitopes were found in blood samples taken from healthy humans, and influenza-infected adults and children. The research team next conducted vaccination tests on mice by using the peptides responsible for activating the killer cells as a form of vaccination. “Our vaccination test studies revealed remarkably reduced levels of flu virus and inflammation in the airways in animal models,” Koutsakos said. “These results show that killer T cells provide unprecedented immunity across all flu viruses, a key component of a potential universal vaccine,” Koutsakos said.