Enhancing Polysaccharide Immunity through Intranasal Immunizations

Abstract

AbstractObjectiveA model conjugate vaccine incorporating a pneumococcal polysaccharide with EcoCRM197 was used to determine vaccine efficacy when administered with our clinical-stage mucosal stimulating adjuvant, NE01. This was the first attempt at combining NE01 with a polysaccharide conjugate vaccine to elicit mucosal immunity against respiratory bacterial infection through intranasal immunizations.ResultsIntranasal immunizations using the NE01 adjuvant incorporating a polysaccharide conjugate resulted in the generation of a robust IgG and IgA responses in both serum and mucosa. Our data also demonstrated the active homing of immunological memory cells to the lower respiratory tract as evidenced by an increase of IgG- and IgA-producing memory B-cells in the lungs. Further, intranasal immunization enhanced the induction of a balanced Th1/Th2/ Th17 immune response with clear homing of memory T-cells to the lungs. Serum antibodies generated by this formulation and route of administration demonstrated excellent efficacy in killing S. pneumonia in an in vitro OPK assay, a biomarker of vaccine efficacy. Our data suggest that further optimization of the dose and schedule as well as evaluation of the efficacy of this new formulation in animal models of colonization and infection are warranted.