Findings show human-to-human transmission of H5N1 more difficult than previously feared.

The requirement for at least two simultaneous genetic mutations to occur before avian strains of flu readily transmit between people could explain why viruses such as H5N1 haven’t yet caused a human pandemic, according to research by scientists in the U.K. and U.S.

Results from the study, by researchers at Imperial College London, the University of Reading, and the University of North Carolina, have also provided new insights into viral transmission that could help the development of a vaccine for the future.

Using in vitro models of human airway epithelia and tissue sections, the researchers studied a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread.

They first found that while H5 viruses can currently only infect ciliated cells in the upper airways, in order to transmit between humans, avian strains would also need to be able to infect nonciliated cells as well.

By manipulating the viral genes, they then demonstrated that two genetic changes would need to occur in the HA gene simultaneously before the virus could infect cells necessary for transmission between humans. The research is published in PLoS ONE in a paper titled, “Mutations in H5N1 Influenza Virus Hemagglutinin That Confer Binding To Human Tracheal Airway Epithelium.”

H5N1 has infected about 400 people since 2003, and has a high mortality rate in humans, at around 60%, the scientists point out. “H5N1 is a particularly nasty virus so when humans started to get infected with bird flu, people started to panic,” explains Imperial College’s professor Wendy Barclay, corresponding author on the PLoS ONE paper. “Thankfully we haven’t had a major outbreak, and this has led some people to ask, “what happened to bird flu? We wanted to know why the virus hasn’t been able to jump from human to human easily. 

“Our new research suggests that it is less likely than we thought that H5N1 will cause a pandemic, because it’s far harder for it to infect the right cells,” she continues. “The odds of it undergoing the kind of double mutation that would be needed are extremely low.”

Nevertheless, the researchers stress, complacency should be avoided. “Our new findings do not mean that this kind of pandemic could never happen,” Professor Barclay continues. “It’s important that scientists keep working on vaccines so that people can be protected if such an event occurs.”

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