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Positive nanoparticle charge increased pulmonary immunization efficacy
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Pulmonary immunization may be more effective when protein-loaded nanoparticles are synthesized with a positive surface charge, according to recent data.
Researchers from the University of North Carolina and North Carolina State University synthesized hydrogel nanoparticles using the Particle Replication in Non-wetting Templates platform (Liquidia Technologies). Nanoparticles were identical in size, shape and antigen loading, with the only difference being a positive or negative surface charge.
“Pulmonary immunization enhances local humoral and cell-mediated mucosal protection, which are critical for vaccination against lung-specific pathogens such as influenza or tuberculosis,” the researchers wrote. “A variety of nanoparticle formulations have been tested preclinically for pulmonary vaccine development, yet the role of nanoparticle surface charge on downstream immune responses remains poorly understood.”
Increased systemic and lung antibody titers were observed after immunization with positively charged ovalbumin-conjugated cationic nanoparticles, while a weaker response was seen when using negatively charged nanoparticles. Additionally, dendritic cells treated with ovalbumin-conjugated cationic nanoparticles ex vivo led to antigen-specific T-cell proliferation 100-fold more potent than treatment with soluble ovalbumin alone.
“Enhanced T-cell expansion correlated with increased expression of surface MHC-II, T-cell coactivating receptors and key cytokines/chemokine expression by dendric cells treated with cationic nanoparticles, which were not observed with anionic nanoparticles or soluble ovalbumin,” the researchers wrote. “These studies highlight the importance of nanoparticle surface charge when designing pulmonary vaccines, and our findings support the notion that cationic nanoparticle platforms engender potent humoral and mucosal immune responses.”
Disclosure: One researcher is a founder and maintains financial interest in Liquidia Technologies, the biopharmaceutical company that produces the PRINT platform.
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