RESUMO
Infections remain a major threat to human lives. To overcome the threat caused by pathogens, mucosal vaccines are considered a promising strategy. However, no inactivated and/or subunit mucosal vaccine has been approved for human use, largely because of the lack of a safe and effective mucosal adjuvant. Here, we show that enzymatically synthesized polymeric caffeic acid (pCA) can act as a potent mucosal adjuvant in mice. Intranasal administration of ovalbumin (OVA) in combination with pCA resulted in the induction of OVA-specific mucosal IgA and serum IgG, especially IgG1. Importantly, pCA was synthesized from caffeic acid and horseradish peroxidase from coffee beans and horseradish, respectively, which are commonly consumed. Therefore, pCA is believed to be a highly safe material. In fact, administration of pCA did not show distinct toxicity in mice. These data indicate that pCA has merit for use as a mucosal adjuvant for nasal vaccine formulations.
Assuntos
Adjuvantes Imunológicos/química , Ácidos Cafeicos/química , Ácidos Cafeicos/imunologia , Animais , Armoracia/química , Ensaios de Migração de Leucócitos , Café/química , Ensaio de Imunoadsorção Enzimática , Feminino , Peroxidase do Rábano Silvestre/metabolismo , Imunoglobulina A/metabolismo , Imunoglobulina G/sangue , Lignina/metabolismo , Lipossomos/administração & dosagem , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The aim of this study was to clarify the mechanism of adjuvant action induced by negatively charged liposomes composed of phosphatidylserine (PS-liposomes). Coculture of mouse splenic adherent cells with ovalbumin (OVA)-specific Th1 clone (42-6A) cells in the presence of PS-liposomes encapsulating OVA resulted in high levels of IL-12 and IFN-gamma productions compared with those of positively charged or neutral liposomes. IL-12 and IFN-gamma productions were dose-dependent on antigens in PS-liposomes. The expression of CD40L on 42-6A cells was enhanced by treatment with PS-liposomes encapsulating OVA. IL-12 production, but not IFN-gamma, was completely inhibited by the addition of anti-CD40L mAb. These results indicate that PS-liposomes encapsulating antigens could enhance antigen-dependent IL-12 production through the interaction between CD40 on macrophage/dendritic cells and CD40L on 42-6A cells.