The Children’s Hospital of Philadelphia Research Institute’s chief scientific officer, Philip R. Johnson, MD, is among the co-authors of a new study that presents an advanced approach to vaccine design. This innovation, in which artificial proteins are custom-designed as vaccine components, offers the promise of a new way to prevent serious childhood infections caused by respiratory syncytial virus (RSV). More broadly, it may enable the creation of new vaccines against evolving, difficult-to-treat diseases such as HIV, influenza and hepatitis C.
The study, which was published recently online in Nature, was led by William R. Schief, PhD, and colleagues from The Scripps Research Institute (TSRI) in La Jolla, Calif. “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 Dr. Schief.
Most existing vaccines use inactivated viruses or similar particles to stimulate the body’s immune system to release infection-fighting antibodies. However, rapidly evolving infectious agents such as HIV have been able to change quickly enough to evade traditional vaccine candidates. As a result, vaccine experts have been working to design new vaccines to elicit broadly neutralizing antibodies that strike against hidden vulnerable structures within quick-changing viruses.
The new strategy uses sophisticated techniques to imitate an epitope — a structure specific to each type of invading virus that is recognized by the immune system. The scientists used a new software application, which they call “Fold from Loops,” to design flexible protein scaffolds to hold the epitope that induces the immune system to produce protective antibodies.
In Nature study, the research team induced potent antibodies in non-human primates against RSV, which commonly makes human babies sick, and kills large numbers of infants worldwide. According to the CDC, each year in the U.S. between 75,000 and 125,000 children under the age of 1 are hospitalized with RSV infections.
The investigators’ successful experiment offers proof-of-principle that this approach is feasible for developing a first RSV vaccine in humans, as well as for developing potential future vaccines against HIV, influenza and hepatitis C.
This work builds on previous laboratory research by Dr. Johnson aimed at finding innovative methods in vaccine design. In 2009, for example, his team published a study in Nature Medicine that used gene therapy to produce antibody-like proteins to protect monkeys from the animal counterpart to HIV. And in May of 2013, Dr. Johnson contributed to a Science study calling for a “Human Vaccines Project” to accelerate the development of new vaccines. In the current study, he performed laboratory experiments using his collaborators’ newly designed proteins.
The Nature study “represents the confluence of recent technological advances in computational biology, structural biology and immune monitoring, and offers great potential for accelerating development of next generation vaccines against major global diseases,” said Senior Vice President and Chief Scientific Officer the International Aids Vaccine Initiative Wayne C. Koff, PhD.
“Bringing these new types of vaccines into clinical use will take years of work, but this study represents an important first step along the way,” noted Dr. Johnson.