Adjuvanting influenza hemagglutinin vaccine with a human pulmonary surfactantmimicking synthetic compound SF-10 induces local and systemic cell-mediated immunity in mice

Abstract

We reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific IgA in nasal and lung washes and IgG in sera with their neutralizing activities. Since CD8+ T cell-mediated protection is an important requirement for adaptive immunity, we investigated in this study the effects of SF-10 with antigen on local and systemic cell-mediated immunity. Nasal instillation of ovalbumin, a model antigen, combined with SF-10 efficiently delivered antigen to mucosal dendritic and epithelial cells and promoted cross-presentation in antigen presenting cells, yielding a high percentage of ovalbumin-specific cytotoxic T lymphocytes in the nasal mucosa, compared with ovalbumin alone. Nasal immunization of HAv-SF-10 also induced HAv-specific cytotoxic T lymphocytes and upregulated granzyme B expression in splenic CD8+ T cells with their high cytotoxicity against target cells pulsed with HA peptide. Furthermore, nasal vaccination of HAv-SF-10 significantly induced higher cytotoxic T lymphocytes-mediated cytotoxicity in the lungs and cervical lymph nodes in the early phase of influenza virus infection compared with HAv alone. Protective immunity induced by HAv-SF-10 against lethal influenza virus infection was partially and predominantly suppressed after depletion of CD8+ and CD4+ T cells (induced by intraperitoneal injection of the corresponding antibodies), respectively, suggesting that CD4+ T cells predominantly and CD8+ T cells partially contribute to the protective immunity in the advanced stage of influenza virus infection. These results suggest that SF-10 promotes effective antigen delivery to antigen presenting cells, activates CD8+ T cells via cross-presentation, and induces cell-mediated immune responses against antigen.