Rational vaccine design
Vaccines are one of the most valuable instruments to prevent and control infectious diseases. Vaccines stimulate the production of neutralizing antibodies, which are their primary correlate of protection. However, most vaccines result in the induction of a broad repertoire of antibodies that target multiple sites of the pathogen proteins, called epitopes. Among those, functional antibodies with key specificities are often rare. Therefore, a central goal in vaccine development is to focus antibody responses on such neutralizing epitopes.
Building precision vaccines
Our lab developed a design strategy that enables the precise induction of neutralizing antibodies against a specific epitope. We use our computational design strategy, TopoBuilder, to build protein topologies that present viral epitopes with atomic-level accuracy. We applied this approach to develop an immunogen cocktail presenting three major antigenic sites of the respiratory syncytial virus (RSV) fusion protein (RSVF). This cocktail, named Trivax, induces a balanced antibody response targeting three defined epitopes, yielding neutralizing serum levels in mice and nonhuman primates (NHPs) after a single boost. Trivax elicits a remarkably focused immune response toward the target antigenic sites.
Our developed strategy presents a blueprint for epitope-centric vaccine design, offering an unprecedented level of control over induced antibody specificities in both naïve and primed antibody repertoires.
References: Sesterhenn F. et al. Science (2020), Sesterhenn F. et al. PLoS biology (2019), Bonet J. et al. PLoS computational biology (2018)