Influenza virus with haemagglutinin (blue)

Wikipedia/M. Eickmann

Scientists have mutated a protein of the H5N1 virus to identify changes which could make the virus capable of passing between humans, and create variants that could be used as pre-emptive vaccines.

The findings are reported by Yang Zhi-Yong and colleagues in the 10 August issue of Science.

The H5N1 virus causes avian influenza, or 'bird flu', which can occasionally be passed to humans. According to the World Health Organization, it has infected more than 300 people worldwide, of whom 192 had died by 25 July this year.

So far no human-to-human transmission of the virus has been reported. Scientists believe that for the H5N1 virus to spread among humans, a mutation must occur in the protein spikes on its surface, known as haemagglutinin (HA). The virus enters a host cell after part of HA, the receptor-binding domain (RBD), has bound to a specific part of the cell.

Scientists at the United States' National Institute of Allergy and Infectious Diseases (NIAID) created specific mutations in the RBD of H5N1 and then tested the ability of the mutated RBD structure to recognise bird and human cells.

Rather than using real H5N1 virus, the researchers altered the RBD of HA protein in artificial forms of the virus –– called pseudoviruses –– which do not cause disease but are otherwise a good model of H5N1.

The researchers believe the method can guide the development of vaccines and therapeutic antibodies "that can be evaluated before the emergence of human-adapted H5N1 strains".

"There is no guarantee that we will find the precise mutations needed to adapt to human [cells], but we can be prepared for most of them and there are probably a limited number of ways the virus can adapt to recognise the receptor [of human cells]," corresponding author Gary J. Nabel of NIAID told SciDev.Net.

He adds that new virus variants made in the study could be used to generate vaccine stocks against possible H5N1 virus mutants.

Dong Xiaoping of the Institute of Virology at the Chinese Centre for Disease Control welcomed the study.

"The HA protein is the most widely used target for vaccines against H5N1 virus. The method might help vaccines developed through different approaches targeting some common areas in the HA proteins," says Dong, who chairs China's ongoing development of human H5N1 vaccine.

"But more studies are needed to test the possible interactions between the identified structural change of the HA protein and the pseudovirus carrying it, as well as the safety issues incurred by the interactions," Dong told SciDev.Net.

Link to full paper in Science

Reference: Science 317, 825 (2007)