Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge.

ABSTRACT: Influenza HA is the primary target of neutralizing antibodies during infection, and its sequence undergoes genetic drift and shift in response to immune pressure. The receptor binding HA1 subunit of HA shows much higher sequence variability relative to the metastable, fusion-active HA2 subunit, presumably because neutralizing antibodies are primarily targeted against the former in natural infection. We have designed an HA2-based immunogen using a protein minimization approach that incorporates designed mutations to destabilize the low pH conformation of HA2. The resulting construct (HA6) was expressed in Escherichia coli and refolded from inclusion bodies. Biophysical studies and mutational analysis of the protein indicate that it is folded into the desired neutral pH conformation competen

SUBMITTER: Bommakanti G 

PROVIDER: S-EPMC2922242 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature