RESUMO
This study describes the feasibility and adjuvant mechanism of a degradable emulsion for tuning adaptive immune responses to a vaccine antigen. We featured a mouse model with ovalbumin (OVA) as the antigen to deepen our understanding of the properties of a degradable emulsion-based adjuvant, dubbed PELC, interacting with immune cells and to elucidate their roles in vaccine immunogenicity in vivo. First, we demonstrated that the emulsion, which is stabilized by an amphiphilic bioresorbable polymer, shows degradation in mimic human body conditions and considerable tolerance in vivo. Then, we confirmed the model protein could be loaded into the emulsion and released from the matrix in a sustained manner, subsequently driving the production of antigen-specific antibodies. We also comprehended that PELC not only recruits antigen-presenting cells (APCs) to the injection site but also induces the activation of the recruited APCs and migration to the draining lymph nodes. As an adjuvant for cancer immunotherapy, PELC-formulated OVA could strongly enhance antigen-specific T-cell responses as well as anti-tumor ability with respected to non-formulated OVA, using OVA protein/EG7 cells as a tumor antigen/tumor cell model. Accordingly, our data paved the way for the clinical application of degradable emulsions based on amphiphilic bioresorbable polymers as vaccine adjuvants.
Assuntos
Adjuvantes Imunológicos , Antígenos de Neoplasias , Poliésteres , Polietilenoglicóis , Vacinas , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacocinética , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos/imunologia , Células Apresentadoras de Antígenos/imunologia , Antígenos de Neoplasias/química , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/farmacologia , Linhagem Celular , Emulsões , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia , Linfócitos T/imunologia , Vacinas/química , Vacinas/imunologia , Vacinas/farmacocinética , Vacinas/farmacologiaRESUMO
Here we investigate the immunogenicity of a combination adjuvant comprising emulsified fine particles (namely PELC) together with LD-indolicidin, a peptiomimetic stereoisomer of the bovine neutrophil peptide indolicidin. We demonstrated that intranasal vaccination with either PELC/LD-indolicidin or Alum enhances protective influenza-specific serological immunity in mice; however, the adjuvant potency of Alum was rather reduced when the mice vaccinated orally with formulated influenza vaccines. The information gathered from this study will enhance our effort in the formulation design as well as the optimization of alternative administration routes for prophylactic vaccines against emerging infectious diseases, in particular pandemic influenza.