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Bird Flu Mutation Study Offers Vaccine Clue

Small genetic changes could cause outbreak in humans (Apr. 8)

Scientists at Imperial College London have described small genetic changes that enable the H5N1 bird flu virus to replicate more easily in the noses of mammals.

So far there have been only isolated cases of bird flu in humans and no widespread transmission as the H5N1 virus cannot replicate efficiently in the nose. The new study, using weakened viruses in the lab, supports the conclusions of controversial research published in 2012, which demonstrated that just a few genetic mutations could enable bird flu to spread between ferrets, which are used to model flu infection in humans.

Researchers say the new findings could help to develop more effective vaccines against new strains of bird flu that can spread between humans.

“Knowing why bird flu struggles to replicate in the nose and understanding the genetic mutations that would enable it to happen are vital for monitoring viruses circulating in birds and for preparing for an outbreak in humans,” said study leader Professor Wendy Barclay.

“The studies published last year pointed to a mechanism that restricts replication of H5N1 viruses in the nose. We’ve engineered a different mutation with the same effect into one of the virus proteins and achieved a similar outcome. This suggests that there is a common mechanism by which bird flu could evolve to spread between humans, but that a number of different specific mutations might mediate that.”

Bird flu rarely infects humans because the human nose has different receptors than those of birds and is also more acidic. The researchers studied mutations in the gene for hemagglutinin, a protein on the surface of the virus that enables it to get into host cells. They carried out their experiments in a laboratory strain of flu with the same proteins on its surface as those of bird flu, but engineered so that it could not cause serious illness.

The study found that mutations in H5 hemagglutinin enabled the protein to tolerate higher levels of acidity. Viruses with these mutations and others that enabled them to bind to different receptors were able to replicate more efficiently in ferrets and to spread from one animal to another.

According to the researchers, the new results have important implications for designing vaccines against potential pandemic strains of bird flu. Live attenuated flu vaccines (LAIVs) may be used in a pandemic situation because it is possible to manufacture many more doses of this type of vaccine than of the killed virus vaccines used to protect against seasonal flu. LAIVs are based on weakened viruses that do not cause illness, but they still have to replicate in order to elicit a strong immune response.

In the new study, viruses with modified hemagglutinin proteins induced strong antibody responses in ferrets, suggesting that vaccines with similar modifications might prove more effective than those tested previously.

Source: Imperial College London; April 8, 2013.

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