Tunable T cell immunity towards a protein antigen using polymersomes vs. solid-core nanoparticles

• Published in: Biomaterials 2013-06, Vol.34 (17), p.4339-4346
• Main Authors: Stano, Armando, Scott, Evan A, Dane, Karen Y, Swartz, Melody A, Hubbell, Jeffrey A
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Antigens - immunology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - secretion; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Degranulation - drug effects; Cell Degranulation - immunology; Cell Proliferation - drug effects; Cytokines - biosynthesis; Cytokines - secretion; Cytotoxicity, Immunologic - drug effects; Dentistry; Female; Flow cytometry; Immune response; Immunity - drug effects; Immunomodulation; Immunostimulation; Mice; Mice, Inbred C57BL; Nanoparticle; Nanoparticles - chemistry; Ovalbumin - immunology; Phenotype; Polyethylene Glycols - pharmacology; Spleen - cytology; Sulfides - pharmacology; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - physiology
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.02.024

Abstract Using poly(propylene sulfide) (PPS) and poly(ethylene glycol) (PEG) as components of a nanocarrier platform, we sought to compare immune responses induced by PPS- bl -PEG polymersomes (PSs; watery-core structures, with antigen incorporated within the PSs) and PEG-stabilized PPS nanoparticles (NPs; solid-core structures, with antigen conjugated upon the NP surface). We have previously shown strong CD8+ T cell responses to antigen conjugated to NPs via a disulfide link, and here we investigated the extent to which antigen incorporated within oxidatively-sensitive PSs could induce CD4+ or CD8+ T cell responses. C57BL/6 mice were subcutaneously immunized with free ovalbumin (OVA) as a model antigen, or equivalent doses of OVA-loaded into PSs, conjugated onto NPs, or given as a mixture of the two. Free CpG was used as an adjuvant. Antigen-loaded PSs induced enhanced frequencies of antigen-specific CD4+ T cells in the spleen, lymph nodes and lungs as compared to the NP formulation, whereas antigen-conjugated NPs induced stronger CD8+ T cell responses. Co-administration of both PSs and NPs elicited T cell immunity characteristic of the two nanocarriers at the same time, i.e. both strong CD4+ and CD8+ T cell responses. These results have important implications for particulate-based vaccine design and highlight the potential of using different antigen-delivery systems for the induction of both T helper and cytotoxic T lymphocyte immune responses.