Vault nanocapsules as adjuvants favor cell-mediated over antibody-mediated immune responses following immunization of mice

• Published in: PloS one 2012-07, Vol.7 (7), p.e38553
• Main Authors: Kar, Upendra K, Jiang, Janina, Champion, Cheryl I, Salehi, Sahar, Srivastava, Minu, Sharma, Sherven, Rabizadeh, Shahrooz, Niazi, Kayvan, Kickhoefer, Valerie, Rome, Leonard H, Kelly, Kathleen A
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - genetics; Albumin; Animals; Antigens; Bacterial diseases; Bacterial infections; Bioengineering; Biology; Cancer; Casing (process); CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell-mediated immunity; Deoxyribonucleic acid; DNA; Drug Compounding; Engineering schools; Female; Gene expression; Genetic engineering; Genetically modified organisms; Health aspects; Humans; Immune response; Immune response (cell-mediated); Immune system; Immunity; Immunity (cell-mediated); Immunity, Cellular - drug effects; Immunity, Humoral - drug effects; Immunization; Immunoglobulin G; Immunoglobulin G - biosynthesis; Immunoglobulin G - immunology; Immunoglobulins; Immunologic Memory - drug effects; Immunological memory; Inflammation; Influenza; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Isotypes; Laboratories; Liposomes; Liposomes - administration & dosage; Liposomes - immunology; Lymphocytes; Lymphocytes T; Medical research; Medicine; Memory cells; Metastasis; Mice; Mucosa; Nanocapsules - administration & dosage; Nanocapsules - chemistry; Nanoparticles; Ovalbumin; Ovalbumin - administration & dosage; Ovalbumin - immunology; Pathology; Pharmaceutical sciences; Proteins; Recombinant Proteins - administration & dosage; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Sucrose; T cells; Vaccines; Vaults; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038553

Modifications of adjuvants that induce cell-mediated over antibody-mediated immunity is desired for development of vaccines. Nanocapsules have been found to be viable adjuvants and are amenable to engineering for desired immune responses. We previously showed that natural nanocapsules called vaults can be genetically engineered to elicit Th1 immunity and protection from a mucosal bacterial infection. The purpose of our study was to characterize immunity produced in response to OVA within vault nanoparticles and compare it to another nanocarrier. We characterized immunity resulting from immunization with the model antigen, ovalbumin (OVA) encased in vault nanocapsules and liposomes. We measured OVA responsive CD8(+) and CD4(+) memory T cell responses, cytokine production and antibody titers in vitro and in vivo. We found that immunization with OVA contain in vaults induced a greater number of anti-OVA CD8(+) memory T cells and production of IFNγ plus CD4(+) memory T cells. Also, modification of the vault body could change the immune response compared to OVA encased in liposomes. These experiments show that vault nanocapsules induced strong anti-OVA CD8(+) and CD4(+) T cell memory responses and modest antibody production, which markedly differed from the immune response induced by liposomes. We also found that the vault nanocapsule could be modified to change antibody isotypes in vivo. Thus it is possible to create a vault nanocapsule vaccine that can result in the unique combination of immunogen-responsive CD8(+) and CD4(+) T cell immunity coupled with an IgG1 response for future development of vault nanocapsule-based vaccines against antigens for human pathogens and cancer.