(545d) Surface Properties of Nanoparticle Vaccines for Potent Pulmonary Mucosal Immunity

Direct pulmonary immunization can provide enhanced local humoral and cell mediated mucosal protection, which is critical for vaccination against lung-specific pathogens such as influenza or tuberculosis.  Nanoparticle formulations for pulmonary vaccines offer potential solutions to overcome biological barriers of the lung, inherently targeting APCs and penetrating the mucosal layer.  A wide variety of particle formulations have been investigated in preclinical studies for pulmonary vaccine development, yet the role of surface charge on downstream immune responses remains poorly understood.  We developed a pair of nanoparticles (NP) with varied surface charge which were covalently attached to a model antigen ovalbumin (OVA) that are otherwise identical in size, shape and antigen loading.  OVA-conjugated cationic NPs were found to induce more potent antigen presenting cells (APCs) than anionic NPs both in vitro and in vivo.  Following treatment with cationic NP-OVA, dendritic cells (DCs) induced strong CD4⁺ OTII T cell proliferation in co-culture at ~10 fold lower concentrations than anionic NP-OVA, which was attributed to increased expression of surface receptors and key cytokines/chemokines. In vivo, pulmonary instillation of cationic NPs resulted in enhanced systemic and lung antibody titers, stemming from sufficient particle association with lung DC populations and active particle transport to draining medistinal lymph nodes.  Our results indicate that particle surface charge is a main variable in driving T-cell dependent antibody responses in vivo and suggest the continued role of cationic NP platforms for engendering potent mucosal responses.