February 5, 2014     Correia, B. E., Bates J. T.,  et al. (2014).  Proof of principle for epitope-focused vaccine design. Nature.

In a widely cited Nature paper entitled Proof of principle for epitope-focused vaccine design, IPD researchers and collaborators invented a new method to design novel proteins for use as a candidate vaccines to protect against respiratory syncytial virus (RSV), a significant cause of infant mortality.  

RSV Immunogen Design Process doi:10.1038/nature12966
RSV Immunogen Design Process doi:10.1038/nature12966

A new computational Rosetta program (Fold From Loops) was developed to design flexible protein scaffolds around a functional fragment of interest – in this case a neutralizing epitope from RSV. These designed protein scaffolds accurately mimicked the viral epitope structure, and scaffold immunization of rhesus macaques induced virus neutralizing activity. This successful proof of concept for epitope-focused vaccine design highlights the potential for this protein design method to generate vaccines for RSV, HIV and other pathogens that have resisted traditional vaccine development.

To learn more about broadly neutralizing antibodies and vaccine design, read the February 2014 Molecule of the Month by David Goodsell at the Protein Data Bank.

Also, Science 2.0 had a nice article on this important breakthrough in application of computational protein design to vaccines. See also this link.