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

Simposio; Simposio; Keystone Symposia "The Modes of Action of Vaccine Adjuvants"; 2014; 2014

Previous results demonstrated that a Brucellaprotein (BP) administered by the oral route has self-adjuvant properties andprompted us to study its potential application as adjuvant for other antigens(Ags). Also, our results indicated that BP is able to inhibit in vitro theactivity of many proteases present at the gastrointestinal tract whichsuggested its potential application in oral vaccine delivery. In BALB/c miceoral delivery of OVA in the presence of BP resulted in a significantlyincreased OVA-specific T cell response (DTH assay) and OVA-specific IFN-gproducing CD4+ and CD8+ T cells at the mucosal (MLNs) and systemic (spleen)level. Furthermore, we assessed BP?s adjuvant capacity in a vaccine formulationagainst an actual pathogen. Oral immunization of BALB/c mice with a heat-killedSalmonella extract (HKS) plus BP resulted in an increase in anti-HKS specificIgA in feces and IgG in serum of immunized animals. Induction of systemic andmucosal cellular response was evidenced by an increment in IL-17 production inspleen as well as higher IFN-g levels both in spleen and MLNs. A significantlyincreased HKS-specific in vivo T cell response (DTH assay) and higher a4b7expression in memory T lymphocytes migrating to the gut were also observed whenthe Ag was co-delivered with BP. Finally, immunization with HKS+BPsignificantly reduced bacterial load in Balb/c mice after oral challenge withvirulent S. Typhimurium. Altogether, our results suggest that BP would be anideal mucosal adjuvant bypassing the harsh environment of the gastrointestinaltract and enhancing Ag-specific immune responses