DNA-Encoded Flagellin Activates Toll-Like Receptor 5 (TLR5), Nod-like Receptor Family CARD Domain-Containing Protein 4 (NRLC4), and Acts as an Epidermal, Systemic, and Mucosal-Adjuvant

Vaccines
Sanna NyströmSteven E Applequist

Abstract

Eliciting effective immune responses using non-living/replicating DNA vaccines is a significant challenge. We have previously shown that ballistic dermal plasmid DNA-encoded flagellin (FliC) promotes humoral as well as cellular immunity to co-delivered antigens. Here, we observe that a plasmid encoding secreted FliC (pFliC(-gly)) produces flagellin capable of activating two innate immune receptors known to detect flagellin; Toll-like Receptor 5 (TLR5) and Nod-like Receptor family CARD domain-containing protein 4 (NRLC4). To test the ability of pFliC(-gly) to act as an adjuvant we immunized mice with plasmid encoding secreted FliC (pFliC(-gly)) and plasmid encoding a model antigen (ovalbumin) by three different immunization routes representative of dermal, systemic, and mucosal tissues. By all three routes we observed increases in antigen-specific antibodies in serum as well as MHC Class I-dependent cellular immune responses when pFliC(-gly) adjuvant was added. Additionally, we were able to induce mucosal antibody responses and Class II-dependent cellular immune responses after mucosal vaccination with pFliC(-gly). Humoral immune responses elicited by heterologus prime-boost immunization with a plasmid encoding HIV-1 from gp160 ...Continue Reading

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Citations

Jun 16, 2018·Journal of Medical Virology·Sumit SharmaLennart Svensson
Nov 23, 2019·International Journal of Cancer. Journal International Du Cancer·Sebastian FelgnerMarc Erhardt
Sep 2, 2017·Experimental & Molecular Medicine·Irshad A HajamJohn Hwa Lee
Feb 20, 2021·Nature Immunology·Katherine A Deets, Russell E Vance

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Datasets Mentioned

BETA
D13689

Methods Mentioned

BETA
PCR
ELISA
transfection
flow cytometry
IgA
glycosylation

Software Mentioned

BLASTP
FlowJo
GraphPad Prism

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