[Medicine] Academia Sinica's Paper Hints at Strategy for Design of Universal Vaccine

[Medicine] Academia Sinica's Paper Hints at Strategy for Design of Universal Vaccine (Chinese Version)

Academia Sinica Newsletter (2009/10/13) A research team led by Academia Sinica President Chi-Huey WONG published an article in the prestigious US scientific journal Proceedings of the National Academy of Sciences (PNAS) this week hinting at the possibility of a new vaccine design that could be applied to vaccines for many strains of influenza such as "swine flu," "bird flu," and perhaps other viral diseases such as Hepatitis C and HIV.

The team, at the Academia Sinica's Genomics Research Center, investigated how the hemagglutinin protein found on the surface of influenza viruses binds to host cells. Specifically, they looked at how glycans (sugar chains) attached to the surface of hemagglutinin affect binding to host cells.

Hemagglutinin – the "H" in H1N1 and H5N1 – is the key molecule that determines the entry of a virus into a host cell, and thus infection of the host by the virus. Therefore its study is of utmost importance in the search for ways to prevent the spread of viral diseases.

The team made the surprising discovery that hemagglutinin stripped of most of its glycans bound more strongly to host molecules than hemagglutinin with more glycans attached to its surface (fully glycosylated hemagglutinin).

The team then went on to investigate the immune response against the hemagglutinins with many glycans attached to their surfaces as well as the "nearly naked" hemagglutinins. They tested these "hemagglutinin vaccines" on mice. They found that the "nearly naked" mono-glycosylated hemagglutinins were able to neutralize a broader spectrum of virus types than the regular fully glycosylated hemagglutinins. They also found that mice given a vaccine made with hemagglutinins with less glycan attached to the surface and then given a lethal dose of influenza virus, had a survival rate increased by up to 50% in comparison with unvaccinated animals.

Up until now, only regular fully glycosylated hemagglutinins have been used in the production of vaccines.

"What we are saying," said Dr. Che MA, one corresponding author of the paper, "is that it might be a better strategy to design vaccines with hemaglutinins stripped of glycans. Scientists have known for a long time that glycans are important to viruses, but they have not known exactly what roles glycans play in terms of their function and immune response." The mono-glycosylated hemagglutinin as a vaccine in this study showed a stronger immune response with broader neutralizing activities against H5N1 and H1N1. "Glycan modeling and the concept of consensus protein sequence in the design are the two keys which pave the way to the development of universal vaccine against influenza and other human viruses." said Dr. Chi-Huey WONG, the team leader.

The technology associated with the discovery has already been licensed to a Miami-based healthcare company OPKO, to initiate development of protein vaccines. OPKO has opened a Taiwan subsidiary, and will work closely with President Wong's team at Academia Sinica.

The full article entitled "Glycans on influenza hemagglutinin affect receptor binding and immune response" can be found in issue of PNAS available in the week starting October 12.


Related Websites: http://www.pnas.org/content/early/2009/10/09/0909696106

Media contacts:
Dr. Che MA, Genomics Research Center, (O) 886-2-2787-1233
Mei-Hui LIN, Public Relations Office, Central Office of Administration, Academia Sinica (Tel) 886-2-2789-8821, (Fax) 886-2-2782-1551, (M) 0921-845-234 mhlin313@gate.sinica.edu.tw


Reference:
Academia Sinica Newsletter 2009/10/13



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