VII Simposio Internacional de Ciencias Farmacéuticas 2019 "VII SICF" -VII Simposio "Diseño, Obtención y Desarrollo de Fármacos"

VII Simposio Internacional de Ciencias Farmacéuticas 2019

VII SICF

Translating pore forming proteins-induced innate immune responses into memory CD8+ T cells for vaccine development

Resumen [ES]

Induction of CD8+ T cell responses against pathogens and cancers is an important goal of modern immunology. Notably, increased ratios of effector/central memory T cells (Tef)/(Tcm) have been described for highly efficacious vaccines. One current approach of translational interest is the use of liposomes encapsulating pore-forming proteins (PFP), such as Listeriolysin O (LLO), which are very effective at priming strong and sustained CD8+ T cell responses. We have been recently shown that Sticholysin II (StII), a PFP from the sea anemone Stichodactyla helianthus, stimulated CD8+ T cells against antigens co-encapsulated into liposomes composed of dipalmitoylphosphatidyl choline and cholesterol (DPPC:Chol). In this work, we demonstrated for the first time that StII shows similar abilities to LLO to induce activation and cross-presentation of OVA in dendritic cells. Remarkably, using an ex vivo ELISPOT assay to monitor INF-γ producing T CD8+ cells with similar properties to Tef, liposomal formulations containing the PFPs induced a strong response of T CD8+ cells specific for OVA-MHC-I. On the other hand, liposomal formulations with equal molar quantities of both PFPs induced comparable frequencies of Tcm-like proliferating INF-γ producing cells to those observed in mice immunized with PFP-free OVA/liposomes. However, mice immunized with liposomes with a different DPPC:Chol molar ratio and containing a higher amount of StII induced increased levels of Tcm-like responses. These results point to the capacity of StII/liposomes to induce T CD8+ responses with properties of both Tef and Tcm supporting their use for the rational design of T cell vaccines against pathogens and cancers.

Resumen [EN]

Induction of CD8+ T cell responses against pathogens and cancers is an important goal of modern immunology. Notably, increased ratios of effector/central memory T cells (Tef)/(Tcm) have been described for highly efficacious vaccines. One current approach of translational interest is the use of liposomes encapsulating pore-forming proteins (PFP), such as Listeriolysin O (LLO), which are very effective at priming strong and sustained CD8+ T cell responses. We have been recently shown that Sticholysin II (StII), a PFP from the sea anemone Stichodactyla helianthus, stimulated CD8+ T cells against antigens co-encapsulated into liposomes composed of dipalmitoylphosphatidyl choline and cholesterol (DPPC:Chol). In this work, we demonstrated for the first time that StII shows similar abilities to LLO to induce activation and cross-presentation of OVA in dendritic cells. Remarkably, using an ex vivo ELISPOT assay to monitor INF-γ producing T CD8+ cells with similar properties to Tef, liposomal formulations containing the PFPs induced a strong response of T CD8+ cells specific for OVA-MHC-I. On the other hand, liposomal formulations with equal molar quantities of both PFPs induced comparable frequencies of Tcm-like proliferating INF-γ producing cells to those observed in mice immunized with PFP-free OVA/liposomes. However, mice immunized with liposomes with a different DPPC:Chol molar ratio and containing a higher amount of StII induced increased levels of Tcm-like responses. These results point to the capacity of StII/liposomes to induce T CD8+ responses with properties of both Tef and Tcm supporting their use for the rational design of T cell vaccines against pathogens and cancers.

Sobre el ponente

Anaixis Del Valle

MsC. Anaixis Del Valle

UH Flag of Cuba
Información Práctica
English (US)
No definido
30 minutos
No definido
Autores
Raymond j
Nogueira cv
MsC. Anaixis Del Valle
Laborde rj
Grubaugha d
Rodíguez a
Fernandez le
Luzardo mc
Acosta Rivero
Higgins d
Cruz leal y
Lima g
Labrada m
Lanio me
Palabras clave
cd8+ t cells
liposomes
listeriolysin o
sticholysin ii
vaccines