Details:

Alternative Title:
PLoS One
Personal Author:
Shukla, Nikunj M. ; Salunke, Deepak B. ; Balakrishna, Rajalakshmi ; Mutz, Cole A. ; Malladi, Subbalakshmi S. ; ... More +
Shukla, Nikunj M. ; Salunke, Deepak B. ; Balakrishna, Rajalakshmi ; Mutz, Cole A. ; Malladi, Subbalakshmi S. ; David, Sunil A. ; Less -
Description:
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 and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. We synthesized a dendrimeric molecule bearing six units of a potent TLR7/TLR8 dual-agonistic imidazoquinoline to explore if multimerization of TLR7/8 would result in altered activity profiles. A complete loss of TLR8-stimulatory activity with selective retention of the TLR7-agonistic activity was observed in the dendrimer. This was reflected by a complete absence of TLR8-driven proinflammatory cytokine and interferon (IFN)-γ induction in human PBMCs, with preservation of TLR7-driven IFN-α induction. The dendrimer was found to be superior to the imidazoquinoline monomer in inducing high titers of high-affinity antibodies to bovine α-lactalbumin. Additionally, epitope mapping experiments showed that the dendrimer induced immunoreactivity to more contiguous peptide epitopes along the amino acid sequence of the model antigen.
Subject:
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Adjuvants, Immunologic
Amino Acid Sequence
Animals
Biology
Cattle
Chemistry
Dendrimers
Epitope Mapping
Female
Humans
Imidazoles
Lactalbumin
Medicine
Models, Molecular
Molecular Sequence Data
Protein Conformation
Quinolines
Rabbits
Research Article
Toll-Like Receptor 7

Source:
PLoS One. 2012 ; 7(8).;
Document Type:
Journal Article ;
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:5402464c17ae4d6359a12699e2449deda440eed39ff05361b11fcba86b805d63
File Type:

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