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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.

Author information

Yoo E1, Salyer ACD1,2, Brush MJH2, Li Y2, Trautman KL2, Shukla NM1, De Beuckelaer A3, Lienenklaus S4, Deswarte K3, Lambrecht BN3, De Geest BG3, David SA2.
1
Department of Medicinal Chemistry , University of Kansas , Lawrence , Kansas 66045 , United States.
2
Department of Medicinal Chemistry , University of Minnesota , Minneapolis , Minnesota 55455 , United States.
3
Department of Pharmaceutics and Center for Inflammation Research , Ghent University , 9000 Ghent , Belgium.
4
Institute for Laboratory Animal Science , Hannover Medical School , 30625 Hannover , Germany.