These days, there is a great deal of concern about whether a novel H7N9 bird flu virus, which has been sporadically infecting people in China, could gain the ability to spread easily among humans, thus setting off another influenza pandemic. But researchers at the Massachusetts Institute of Technology warn of a possible threat from a different direction — H3N2 viruses that are currently found in birds and pigs.
A H3N2 virus caused a pandemic during 1967-68, and strains of that virus continue to circulate among humans, leading to outbreaks of seasonal flu. The current flu vaccine therefore includes protection against this sort of virus.
A key viral surface protein, haemagglutinin (HA) allows the flu virus to latch on to and thereby gain entry into cells lining the human airway. It is also the main target of human antibodies.
It was thought that a flu pandemic occurred when a virus with an entirely new sort of HA began to spread among people. As such a virus had not infected humans before, their immune systems would not recognise the HA and be able to quickly mount an antibody response to block infection.
Then came the pandemic of 2009, which was caused by a H1N1 virus. Another H1N1 virus had produced a pandemic 90 years earlier. (The ‘H1’ indicates the sort of HA the virus possessed.)
In a study published recently in the journal Scientific Reports , a team led by Ram Sasisekharan, Alfred H. Caspary Professor of Biological Engineering at MIT, examined key spots on the HA that antibodies bind to as well as the attachment of sugar molecules to the protein (known as glycosylation). Such glycosylation can mask a binding site, blocking an antibody’s access to it.
After the pandemic of 1918, the H1N1 virus continued to circulate among humans. However, these seasonal flu strains developed changes to the antibody-binding sites and glycosylation pattern in order to duck an antibody response.
Consequently, in the following decades, the human immune system responded to those changes and lost the ability to recognise the HA of the 1918 virus. The 2009 pandemic strain’s HA had antibody-binding sites that were 80 per cent similar to that of the 1918 virus and with a similar glycosylation pattern.
A replay of that scenario could happen with H3N2. “The HAs of some currently circulating swine and avian H3 viruses resemble the ‘old’ 1968 pandemic H3N2 HA, and thus could easily jump back to humans now that immunity to it has dropped,” said Dr. Sasisekharan in an email. “Our study highlights the critical need to monitor these swine and avian viruses.”
The study also found that the current H3N2 vaccine strain would not provide protection against these animal viruses. However, a cocktail of H3N2 viruses could be used to formulate a pandemic vaccine, the paper suggested. Animal studies were needed to create an effective cocktail and prepare for a potential re-emergence of a H3N2 pandemic, it added.
