Oral co-administration of a bacterial protease inhibitor in a vaccine formulation increases antigen delivery and immunogenicity

GABRIELA RISSO; ANDRÉS IBAÑEZ; MARIANELA CARABAJAL; LORENA CORIA; LAURA BRUNO; KARINA PASQUEVICH; GABRIEL BRIONES; JULIANA CASSATARO

Seattle

Simposio; Keystone Symposia on Molecular and Cellular Biology: The modes of action of Vaccine adjuvant; 2014

Keystone Symposia

Previous results demonstrated that a Brucella protein (BP) administered by the oral route has self-adjuvant properties and prompted us to study its potential application as adjuvant for other antigens (Ags). Also, our results indicated that BP is able to inhibit in vitro the activity of many proteases present at the gastrointestinal tract which suggested its potential application in oral vaccine delivery. BALB/c mice oral delivered OVA in the presence of BP resulted in a significantly increased OVA-specific T cell response (DTH assay) and OVA-specific IFN-γ producing CD4+ and CD8+ T cells at the mucosal (MLNs) and systemic (spleen) level. Furthermore, we assessed BP?s adjuvant capacity in a vaccine formulation against an actual pathogen. We showed that in BALB/c mice oral delivery of a heat-killed Salmonella extract (HKS) in the presence of BP resulted in an increase in anti-HKS specific IgA in feces and IgG in serum of immunized animals. Induction of systemic and mucosal cellular response was evidenced by an increment in IL-17 production in spleen as well as higher IFN gamma levels both in spleen and MLNs. A significantly increased HKS-specific in vivo T cell response (DTH assay) and higher  expression in memory T lymphocytes migrating to the gut were also observed when the Ag was co-delivered with BP. When challenged with virulent S. Typhimurium, mice immunized with HKS+BP induced lower CFU burden than those immunized with HKS alone. Altogether, our results suggest that BP would be an ideal mucosal adjuvant bypassing the harsh environment of the gastrointestinal tract and enhancing Ag-specific immune responses. This work was supported by Bill & Melinda Gates Foundation through the Grand Challenges Explorations Initiative and by the Agencia Nacional de Promoción Científica y Tecnológica (Argentina).