Induction of Cytotoxic T-Lymphocyte Responses Upon Subcutaneous Administration of a Subunit Vaccine Adjuvanted With an Emulsion Containing the Toll-Like Receptor 3 Ligand Poly(I:C)

Frontiers in Immunology
Signe Tandrup SchmidtDennis Christensen

Abstract

There is an unmet medical need for new subunit vaccines that induce cytotoxic T-lymphocyte (CTL) responses to prevent infection with a number of pathogens. However, stimulation of CTL responses via clinically acceptable subcutaneous (s.c.) and intramuscular (i.m.) injection is challenging. Recently, we designed a liposomal adjuvant [cationic adjuvant formulation (CAF)09] composed of the cationic lipid dimethyldioctadecylammonium (DDA) bromide, a synthetic monomycoloyl glycerol analog and polyinosinic:polycytidylic acid, which induce strong CTL responses to peptide and protein antigens after intraperitoneal administration. By contrast, CAF09 does not stimulate CTL responses upon s.c. or i.m. injection because the vaccine forms a depot that remains at the injection site. Hence, we engineered a series of nanoemulsions (CAF24a-c) based on the active components of CAF09. The oil phase consisted of biodegradable squalane, and the surface charge was varied systematically by replacing DDA with zwitterionic distearoylphosphoethanolamine. We hypothesized that the nanoemulsions drain to the lymph nodes to a larger extent than CAF09, upon s.c. co-administration with the model antigen chicken egg ovalbumin (OVA). This results in an increase...Continue Reading

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Citations

Jan 10, 2019·ILAR Journal·Signe Tandrup SchmidtDennis Christensen
Jul 11, 2021·Scientific Reports·Srijita BasakAnurag P Srivastava
Sep 12, 2020·Chemical Reviews·Wen-Hao Li, Yan-Mei Li

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Methods Mentioned

BETA
dynamic light scattering
flow cytometry
enzyme-linked immunosorbent assay
confocal microscopy
ELISA

Software Mentioned

FlowJo
GraphPad Prism
Zetasizer
GraphPad

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