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| Content Provider | PubMed Central |
|---|---|
| Author | Wong, Pamela T. Leroueil, Pascale R. Smith, Douglas M. Ciotti, Susan Bielinska, Anna U. Janczak, Katarzyna W. Mullen, Catherine H. Groom, Jeffrey V. Taylor, Erin M. Passmore, Crystal Makidon, Paul E. O’konek, Jessica J. Myc, Andrzej Hamouda, Tarek Baker, James R. |
| Editor | Renukaradhya, Gourapura J. |
| Copyright Year | 2015 |
| Abstract | Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate formulations consisting of oil-in-water nanoemulsions that contain various cationic and nonionic surfactants. To facilitate adjuvant development we first evaluated this library in a series of high-throughput, in vitro assays for activities associated with innate and adaptive immune activation in vivo. These in vitro assays screened for the ability of the adjuvant to bind to mucin, induce cytotoxicity, facilitate antigen uptake in epithelial and dendritic cells, and activate cellular pathways. We then sought to determine how these parameters related to adjuvant activity in vivo. While the in vitro assays alone were not enough to predict the in vivo adjuvant activity completely, several interesting relationships were found with immune responses in mice. Furthermore, by varying the physicochemical properties of the surfactant components (charge, surfactant polar head size and hydrophobicity) and the surfactant blend ratio of the formulations, the strength and type of the immune response generated (TH1, TH2, TH17) could be modulated. These findings suggest the possibility of using high-throughput screens to aid in the design of custom adjuvants with unique immunological profiles to match specific mucosal vaccine applications. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0126120 |
| Starting Page | 126120 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 5 |
| Volume Number | 10 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2015-05-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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