Back

Pavlos C. Englezou

Pavlos C. Englezou

The Institute of Virology and Immunology (IVI), Germany

Title: Cationic Lipids efficiently deliver self-amplifying RepRNA for translation in DC and monocytes.

Biography

Pavlos Englezou is a Post-Doctoral Scientist in the Immunology Department at the Institute of Virology and Immunology in Mittelhäusern, Switzerland who has joined the group of Dr. Kenneth C. McCullough since 2013 and is working as part of the European UNIVAX consortium. Pavlos completed his Ph.D. at the University of Manchester in the UK. His research interests lie in the development of novel vaccination strategies using nanotechnology. More specifically his work examines the capacity of cationic lipids to deliver self-replicating RNA to porcine dendritic cells as part of a new vaccination strategy against Influenza A viruses.

Abstract

While host immune defences protect against pathogenic infections, it is critical that host immunity be robust to defend against such infections. Vaccine targeting of dendritic cells (DCs) is an important consideration. Advances in RNA technology have provided high potential in this area, with replicon (RepRNA) vaccines from either positive or negative RNA strand viruses. RepRNA will translate self-replicate without producing infectious progeny; this provides high levels of antigen expression of the inserted genes of interest, mimicking viral infections and inducing both humoural and cellular immunity. Synthetic delivery can target dendritic cells (DC), but require replicons from positive strand viruses – negative strand virus replicons require co-delivery of their polymerase. These investigations examined the interaction with RepRNA from the non-cytopathogenic Classical Swine Fever Virus (CFSV), promoting replication and translation without destroying the targeted DC (a drawback with cytopathogenic replicons). Cationic lipids were assessed for delivery and facilitating RepRNA translation. Whereas RepRNA alone interacted inefficiently with DC, the lipids provided a powerful assistance to the DCs for both delivery and translation. It was considered that the cationic nature of the lipids promoted endosomal escape, essential for facilitating RepRNA translation. However, there was disparity between efficient delivery and translation. Lipids promoting translation were not the most effective for delivery, which relates to observations that RepRNA delivery requirements are distinct from those for oliRNA. Both in vitro and in vivo studies have characterized the lipid-mediated binding and delivery of RepRNA to DC populations, leading to translation of the encoded influenza virus antigens of interest.