doi:10.1038/nindia.2010.114 Published online 19 August 2010
Researchers have now developed an immunogen — an antigen that provokes an immune response — against the influenza virus H3N2. The HA6 antigen developed from the H3N2 influenza virus was found to provide protection against the virus in experimental mice.
The HA protein has two sub-units — HA1 and HA2 — on the outer surface of the viral cell membrane. The HA proteins are used by antibodies to neutralize the infection as a first point of defence. However, viral mutation changes the sequence of the HA1 subunit, allowing the virus to escape by binding to HA1-directed antibodies. As a result, conventional vaccines must be altered every year.
Researchers have now been able to produce antibodies against the conserved HA2 subunit, which is typically considered not to play a major role in the recovery from natural infection. The researchers incorporated HA6, a designed mutation that does not alter the conformation of HA2, using the protein-minimization approach.
"Injecting mice with the redesigned immunogen protected them from influenza virus, although temporary weight loss was observed upon infection," says Raghavan Varadarajan of the Molecular Biophysics Unit at the Indian Institute of Science, Bangalore, and one of the authors of the study.
This approach is significant because it derives antibodies against the relatively conserved stem region of the HA subunit. It could also be seen as a potential vaccine development model for future pandemics.
- Bommakanti, G. et al. Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge. Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1007465107 (2010)