An international team of scientists have designed a new generation of universal flu vaccines to protect against future global pandemics that could kill millions.
The vaccine could give protection for up to 88% of known flu strains worldwide in a single shot, spelling the end of the winter flu season. The collaboration involving the universities of Lancaster, Aston and Complutense in Madrid have applied ground-breaking computational techniques to design the vaccine in a study published in the leading journal Bioinformatics.
The researchers have devised two universal vaccines;
- a USA-specific vaccine with coverage of 95% of known US influenza strains
- a universal vaccine with coverage of 88% of known flu strains globally
Dr Derek Gatherer of Lancaster University said: “Every year we have a round of flu vaccination, where we choose a recent strain of flu as the vaccine, hoping that it will protect against next year’s strains. We know this method is safe, and that it works reasonably well most of the time.
“However, sometimes it doesn’t work – as in the H3N2 vaccine failure in winter 2014-2015 – and even when it does it is immensely expensive and labour-intensive. Also, these yearly vaccines give us no protection at all against potential future pandemic flu.” Previous pandemics include the “Spanish flu” of 1918, and the two subsequent pandemics of 1957 and 1968, which led to millions of deaths.
Even today, the World Health Organisation says that annual flu epidemics are estimated to cause up to half a million deaths globally. Dr Gatherer said: “It doesn’t have to be this way. Based on our knowledge of the flu virus and the human immune system, we can use computers to design the components of a vaccine that gives much broader and longer-lasting protection.”
Dr Pedro Reche of Complutense University said: “A universal flu vaccine is potentially within reach. The components of this vaccine would be short flu virus fragments – called epitopes – that are already known to be recognized by the immune system. Our collaboration has found a way to select epitopes reaching full population coverage.
Dr Darren Flower of Aston University said: “Epitope-based vaccines aren’t new, but most reports have no experimental validation. We have turned the problem on its head and only use previously-tested epitopes. This allows us to get the best of both worlds, designing a vaccine with a very high likelihood of success.”
The team are now actively seeking partners in the pharmaceutical industry to synthesize their vaccine for a laboratory proof-of-principle test.
Learn more: Universal flu vaccine designed by scientists
A rare and improbable mutation in a protein encoded by an influenza virus renders the virus defenseless against the body’s immune system. This University of Rochester Medical Center discovery could provide a new strategy for live influenza vaccines in the future.
A new approach to the live flu vaccine would be particularly advantageous right now after the Centers for Disease Control and Prevention stopped recommending use of the live attenuate flu vaccine, FluMist® earlier this year. Several studies found that the pain-free nasal spray, which was used in about one-third of young children in the U.S., offered no protection to that especially vulnerable population. The flu shot, on the other hand, performed well and the CDC recommends using this vaccine in place of FluMist®.
“There is a need to understand what’s happening with the existing live vaccine and potentially a need to develop a new one,” said David Topham, Ph.D., Marie Curran Wilson and Joseph Chamberlain Wilson Professor of Microbiology and Immunology at URMC and author of the study. “We proposed that the mutation we found could be used to create a live vaccine.”
The mutation weakens the flu virus by making the flu-encoded protein, called Non-Structural 1 (NS1), defunct. Flu virus needs NS1 to prevent interferon, the immune system’s front line against viruses, from alerting the host cell that it has been infected. Inhibiting interferon affords the virus time to multiply and spread before the immune system can mount an attack.
Most people have healthy interferon responses and would quickly and easily fend off this weakened mutant strain of flu, but, “this virus somehow managed to find the one person that had an interferon defect that allowed it to replicate,” said Topham.
The probability of this virus surviving and infecting a human is so low – it is as if Topham and lead study author, Marta Lopez de Diego, Ph.D., research assistant professor of Microbiology and Immunology, found a needle in a haystack. The pair isolated the mutated virus from a nasal swab of a single flu sufferer who happened to be among the small percentage of people with inadequate interferon responses. When they looked for the NS1 mutation in a national database, it showed up in just 0.03 percent of all flu strains reported.
This naturally-occurring “attenuating” flu mutation could provide a new way to make live flu vaccines, which contain viruses that are alive, but “attenuated”, or weakened, so the vaccine itself does not cause illness in humans. Topham and Lopez de Diego suspect their NS1 mutation could be a great way to prevent viruses in the live vaccine from infecting anyone who has normal interferon responses, which is most people.
The study, published online in the Journal of Virology, also highlights the importance of flu virus surveillance – conducting studies like Topham’s to see how the flu is changing, what flu mutations are circulating in humans and animals, and how those mutations affect virus function.
Topham believes health leaders are not doing enough of that research. “The influenza field is largely fixated on studying pandemic or potential pandemic viruses, but those viruses only infect a few dozen people every year whereas seasonal flu infects millions – and yet we don’t study human influenzas closely enough.”
In fact, the World Health Organization estimates 1 billion flu infections each year, causing 300,000 to 500,000 deaths.
Until recently, researchers believed that proteins like NS1 did not change much from strain to strain and season to season, but Topham’s study and others show that NS1 mutations occur naturally and can affect its ability to suppress immunity. Monitoring for these mutations in nature could help us produce better vaccines that save more lives.
A relatively unknown molecule that regulates metabolism could be the key to boosting an individual’s immunity to the flu – and potentially other viruses – according to research reported today in the journal Immunity.
The study, led by University of Vermont (UVM) College of Medicine doctoral student Devin Champagne and Mercedes Rincon, Ph.D., a professor of medicine and an immunobiologist, discovered that a protein called methylation controlled J – or MCJ – can be altered to boost the immune system’s response to the flu.
Metabolism is a crucial function that helps keep cells alive. It plays a role in a range of bodily processes – from the conversion of food into energy to the ability to fight off infection. MCJ is the part of the cell that produces energy and enables metabolism.
“It’s the engine of the cell,” says Rincon, who adds that previously, researchers assumed that the mitochondria were constantly active.