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Hyaluronic acid conjugates of TLR7/8 agonists for targeted delivery to secondary lymphoid tissue

(2018) BIOCONJUGATE CHEMISTRY. 29(8). p.2741-2754
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Abstract
Immunogens carried in lymphatic fluid drain via afferent vessels into regional lymph nodes and facilitate the efficient induction of appropriate immune responses. The lymphatic system possesses receptors recognizing hyaluronic acid (HA). Covalent conjugates of small-molecule TLR7/8 agonists with HA are entirely devoid of immunostimulatory activity in vitro. In murine models of immunization, however, such conjugates traffic to lymph nodes, where they are "unmasked", releasing the small molecule TLR7/8 agonist from the carrier polysaccharide. The resulting focal immunostimulation is manifested in potent adjuvantic effects with negligible systemic exposure. The efficient delivery of immunogens has been a major challenge in the development of subunit vaccines, and enhancing targeted delivery of immunogens to secondary lymphoid organs might be a promising approach for improving vaccine efficacy, as well as safety.
Keywords
T-CELL RESPONSES, IMMUNE-RESPONSE, LYMPHATIC-SYSTEM, CANCER-THERAPY, RECEPTOR 7, IN-VIVO, B-CELLS, VACCINE, NODE, RESIQUIMOD

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Citation

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Chicago
Yoo, Euna, Alex CD Salyer, Michael JH Brush, Yupeng Li, Kathryn L Trautman, Nikunj M Shukla, Ans De Beuckelaer, et al. 2018. “Hyaluronic Acid Conjugates of TLR7/8 Agonists for Targeted Delivery to Secondary Lymphoid Tissue.” Bioconjugate Chemistry 29 (8): 2741–2754.
APA
Yoo, E., Salyer, A. C., Brush, M. J., Li, Y., Trautman, K. L., Shukla, N. M., De Beuckelaer, A., et al. (2018). Hyaluronic acid conjugates of TLR7/8 agonists for targeted delivery to secondary lymphoid tissue. BIOCONJUGATE CHEMISTRY, 29(8), 2741–2754.
Vancouver
1.
Yoo E, Salyer AC, Brush MJ, Li Y, Trautman KL, Shukla NM, et al. Hyaluronic acid conjugates of TLR7/8 agonists for targeted delivery to secondary lymphoid tissue. BIOCONJUGATE CHEMISTRY. 2018;29(8):2741–54.
MLA
Yoo, Euna, Alex CD Salyer, Michael JH Brush, et al. “Hyaluronic Acid Conjugates of TLR7/8 Agonists for Targeted Delivery to Secondary Lymphoid Tissue.” BIOCONJUGATE CHEMISTRY 29.8 (2018): 2741–2754. Print.
@article{8582825,
  abstract     = {Immunogens carried in lymphatic fluid drain via afferent vessels into regional lymph nodes and facilitate the efficient induction of appropriate immune responses. The lymphatic system possesses receptors recognizing hyaluronic acid (HA). Covalent conjugates of small-molecule TLR7/8 agonists with HA are entirely devoid of immunostimulatory activity in vitro. In murine models of immunization, however, such conjugates traffic to lymph nodes, where they are {\textacutedbl}unmasked{\textacutedbl}, releasing the small molecule TLR7/8 agonist from the carrier polysaccharide. The resulting focal immunostimulation is manifested in potent adjuvantic effects with negligible systemic exposure. The efficient delivery of immunogens has been a major challenge in the development of subunit vaccines, and enhancing targeted delivery of immunogens to secondary lymphoid organs might be a promising approach for improving vaccine efficacy, as well as safety.},
  author       = {Yoo, Euna and Salyer, Alex CD and Brush, Michael JH and Li, Yupeng and Trautman, Kathryn L and Shukla, Nikunj M and De Beuckelaer, Ans and Lienenklaus, Stefan and Deswarte, Kim and Lambrecht, Bart and De Geest, Bruno and David, Sunil A},
  issn         = {1043-1802},
  journal      = {BIOCONJUGATE CHEMISTRY},
  language     = {eng},
  number       = {8},
  pages        = {2741--2754},
  title        = {Hyaluronic acid conjugates of TLR7/8 agonists for targeted delivery to secondary lymphoid tissue},
  url          = {http://dx.doi.org/10.1021/acs.bioconjchem.8b00386},
  volume       = {29},
  year         = {2018},
}

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