Potent Adjuvanticity of a Pure TLR7-Agonistic Imidazoquinoline Dendrimer

• DOI: 10.1371/journal.pone.0043612
• Publication Date: 2012-08-28T21:52:03Z
• Authors: Nikunj M. Shukla; Deepak B. Salunke; Rajalakshmi Balak...; Cole A. Mutz; Subbalakshmi S. M...; Sunil A. David
• Keywords: Proinflammatory cytokine; TLR7

Engagement of toll-like receptors (TLRs) serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary anamnestic responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine We synthesized a dendrimeric molecule bearing six units potent TLR7/TLR8 dual-agonistic imidazoquinoline explore if multimerization TLR7/8 would result in altered activity profiles. A complete loss TLR8-stimulatory selective retention the TLR7-agonistic was observed dendrimer. This reflected by absence TLR8-driven interferon (IFN)-γ induction human PBMCs, preservation TLR7-driven IFN-α induction. The dendrimer found superior monomer high titers high-affinity antibodies bovine α-lactalbumin. Additionally, epitope mapping experiments showed that induced immunoreactivity more contiguous peptide epitopes along amino acid sequence model antigen.