The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity
Open accessAbstract
The efficacy of vaccine adjuvants such as Toll-like receptor agonists (TLRa) can be improved through formulation and delivery approaches. Here, we attached small molecule TLR-7/8a to polymer scaffolds (polymer–TLR-7/8a) and evaluated how different physicochemical properties of the TLR-7/8a and polymer carrier influenced the location, magnitude and duration of innate immune activation in vivo. Particle formation by polymer–TLR-7/8a was the most important factor for restricting adjuvant distribution and prolonging activity in draining lymph nodes. The improved pharmacokinetic profile by particulate polymer–TLR-7/8a was also associated with reduced morbidity and enhanced vaccine immunogenicity for inducing antibodies and T cell immunity. We extended these findings to the development of a modular approach in which protein antigens are site-specifically linked to temperature-responsive polymer–TLR-7/8a adjuvants that self-assemble into immunogenic particles at physiologic temperatures in vivo. Our findings provide a chemical and structural basis for optimizing adjuvant design to elicit broad-based antibody and T cell responses with protein antigens.
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Cites
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Cited by
Rodell, C. B., Arlauckas, S. P., Cuccarese, M. F., Garris, C. S., Li, R., Ahmed, M. S., Kohler, R. H., Pittet, M. J., & Weissleder, R. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0236-8 · Cited by 1,099
Towards personalized, tumour-specific, therapeutic vaccines for cancer
Hu, Z., Ott, P. A., & Wu, C. J. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.131 · Cited by 1,067
Novel approaches for vaccine development
Gebre, M. S., Brito, L. A., Tostanoski, L. H., Edwards, D. K., Carfi, A., & Barouch, D. H. (2021) · Cell · doi:10.1016/j.cell.2021.02.030 · Cited by 347
Evolution of macromolecular complexity in drug delivery systems
Kakkar, A., Traverso, G., Farokhzad, O. C., Weissleder, R., & Langer, R. (2017) · Nature Reviews Chemistry · doi:10.1038/s41570-017-0063 · Cited by 320
Designing spatial and temporal control of vaccine responses
Roth, G. A., Picece, V. C. T. M., Ou, B. S., Luo, W., Pulendran, B., & Appel, E. A. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00372-2 · Cited by 316
Metadata
- Authors
- Lynn, G. M., Laga, R., Darrah, P. A., Ishizuka, A. S., Balaci, A. J., Dulcey, A. E., Pechar, M., Pola, R., Gerner, M. Y., Yamamoto, A., Buechler, C. R., Quinn, K. M., Smelkinson, M. G., Vanek, O., Cawood, R., Hills, T., Vasalatiy, O., Kastenmüller, K., Francica, J. R., Stutts, L., Tom, J. K., Ryu, K. A., Esser-Kahn, A. P., Etrych, T., Fisher, K. D., Seymour, L. W., & Seder, R. A.
- Venue
- Nature Biotechnology
- Published
- 2015-10-26
- Volume
- 33
- Issue
- 11
- Pages
- 1201-1210
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2144733364
- Cited by
- 440
- References
- 51
- FWCI
- 14.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Lynn, G. M., Laga, R., Darrah, P. A., Ishizuka, A. S., Balaci, A. J., Dulcey, A. E., Pechar, M., Pola, R., Gerner, M. Y., Yamamoto, A., Buechler, C. R., Quinn, K. M., Smelkinson, M. G., Vanek, O., Cawood, R., Hills, T., Vasalatiy, O., Kastenmüller, K., Francica, J. R., . . . Seder, R. A. (2015). In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity. Nature Biotechnology. https://doi.org/10.1038/nbt.3371
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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