Rationeel ontwerp van een therapeutisch vaccin tegen HIV-1 gebaseerd op een nieuwe formulering van nanopartikel

Recent data demonstrate the feasibility of dendritic cell based therapeutic vaccines to control HIV-1 infection. Nevertheless, their patient specific nature, the specialized infrastructure, the high level of expertise required for preparation and the high demands for storage and transportation preclude widespread application and commercialization. Therefore novel vaccine candidates that retain the power of a DC-based vaccine but at the same time overcome its limitations need to be developed. mRNA based vaccines offer significant promise in this respect. It was shown that mRNA is selectively taken up by dendritic cells upon injection in the lymph node and induces strong antigen specific immune responses. Therefore, an interesting vaccine candidate could be an mRNA-based vaccine able to deliver both a rationally designed HIV antigen sequence and on the other hand potent activation signals. An important drawback of this approach is the fact that intranodal immunization is not easily applicable in clinical settings. Therefore, more standardized routes of administration need to be explored. Given the inherent sensitivity of RNA to ambient RNases, these approaches will require protection of mRNA. In this project we will evaluate the feasibility of delivering an mRNA based therapeutic vaccine with biodegradable nanoparticles loaded with RNA entrapped at their surface through a lysine-derived polylactic acid based polymer.