Setback for flu vax research

The quest for a universal influenza vaccine has taken a hit with the discovery that the prime target is more mutable than previously thought.

The influenza virus is both widespread and prone to rapid mutation, meaning that every year millions of doses of vaccine are manufactured based on the four most prominent strains recorded during the previous flu season in the opposite hemisphere.

The process is time and resource intensive, and is susceptible to failure. This year, for instance, Australia experienced its worst flu season in many tears, due to the rapid spread of a virulent strain not covered by the quadrivalent vax.

Current vaccine formulations target changes to the haemagglutinin protein that covers the outside of the flu virus. The protein looks a little like a mushroom, possessing a head and stalk.

The head of the protein has been shown to change often, and is key to how the virus each year competes against the vaccine developed to defeat it.

Virologists have often suggested, however, that a vaccine potentially targeting the protein’s stalk could function as a universal vax, requiring, in theory, only one inoculation in life. This is because the stalk has been thought to be unchanging.

Research published in the journal Scientific Reports, however, finds that faith placed in its unchanging nature has been misplaced.

Research led by David Topham at the University of Rochester Medical Centre in the US found that while the stalk is indeed more stable than the head, it can still undergo changes when under immune pressure. When this happens, the scientists report, the virus can retain both fitness and virulence, theoretically evading any vaccine developed to defeat it.

To make their findings, Topham and his colleagues analysed the genetic sequences of the H1N1 flu virus from 1918 onwards. They then tested several variants against human antibodies.

The results showed that while the head underwent multiple changes across history and in response to antibody attack, the stalk also altered, although less frequently.

The results imply that research into a universal flu vaccine cannot assume that its prime target is stable.

“The good news is that it’s much more difficult to drive mutations in the stalk, but it’s not impossible,” says Topham.

“A universal flu vaccine based on the stalk would be more broadly protective than the ones we use now, but this information should be taken into account as we move forward with research and development.”