Scripps Research Institute scientists

Scientists at The Scripps Research Institute (TSRI) have invented a new method for designing artificial proteins, and have used it to make key ingredients for a candidate vaccine against a dangerous virus, respiratory syncytial virus (RSV), a significant cause of infant mortality. The virus has been resistant to current vaccine-design strategies.

With the help of collaborating laboratories, the scientists were able to apply the new method, which uses a "rational design" approach to making vaccines focused on specific binding areas (epitopes) on the virus. The result was designer vaccine proteins that the scientists showed stimulate the production of the desired virus-neutralizing antibodies in rhesus macaques.   http://skincareprograms.tumblr.com/post/75567159015/skin-care-products-how-to-skin-care
"This was a proof-of-principle demonstration of a technology that could be very useful against HIV, influenza and other highly variable viruses that have been difficult to stop using traditional vaccine-design strategies," said William R. Schief, associate professor of immunology at TSRI.

The research is reported in by the journal Nature.

Folding from Loops

The new protein-design method represents a significant advance over previous methods.

"One approach we and others have taken has been to transplant a protein fragment of interest, for example one that mimics a particular structure on a virus, onto an existing protein 'scaffold,'" said TSRI Research Associate Bruno E. Correia, a member of the Schief laboratory at the time of the study and lead author of the new report. "While this approach often works well to mimic the structure of a viral epitope, it has never successfully induced neutralizing antibodies, and in some cases this method falls short of even producing viable vaccine candidates."

In these difficult cases, the scaffold structure fails to stabilize the transplanted fragment, resulting in an imperfect mimic of the virus and consequent loss of immune-stimulating properties.

The TSRI scientists wanted a way to design scaffold proteins from scratch - proteins that would fit around their functional fragments more naturally, and would do a better job of stabilizing them.

The result was a new software app, "Fold from Loops," for designing proteins that fold up around a functional fragment of interest. For a proof-of-principle demonstration, the scientists decided to attempt one of the most important current protein-design challenges: making a new protein that mimics a particular epitope on a virus, and thus can serve as a key component of a vaccine.

The Promise of Rational Vaccine Design

Researchers want to be able to stimulate antibody reactions against highly specific epitopes because some infectious agents seem unstoppable by traditional methods of immunization.