Dendritic cell–specific intercellular adhesion molecule‐3‐grabbing nonintegrin (DC‐SIGN) is a cellular receptor for delta inulin adjuvant

Author:

Stewart Erica L123ORCID,Counoupas Claudio123,Steain Megan13,Ashley Caroline13,Alca Sibel13,Hartley‐Tassell Lauren4,von Itzstein Mark4ORCID,Britton Warwick J2,Petrovsky Nikolai5,Triccas James A123ORCID

Affiliation:

1. Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health The University of Sydney Camperdown NSW Australia

2. Centre for Infection and Immunity, Centenary Institute The University of Sydney Camperdown NSW Australia

3. School of Medical Sciences, Faculty of Medicine and Health The University of Sydney Camperdown NSW Australia

4. Institute for Glycomics Griffith University Southport QLD Australia

5. Vaxine Pty Ltd Adelaide SA Australia

Abstract

AbstractDelta inulin, or Advax, is a polysaccharide vaccine adjuvant that significantly enhances vaccine‐mediated immune responses against multiple pathogens and was recently licensed for use in the coronavirus disease 2019 (COVID‐19) vaccine SpikoGen. Although Advax has proven effective as an immune adjuvant, its specific binding targets have not been characterized. In this report, we identify a cellular receptor for Advax recognition. In vitro uptake of Advax particles by macrophage cell lines was substantially greater than that of latex beads of comparable size, suggesting an active uptake mechanism by phagocytic cells. Using a lectin array, Advax particles were recognized by lectins specific for various carbohydrate structures including mannosyl, N‐acetylgalactosamine and galactose moieties. Expression in nonphagocytic cells of dendritic cell–specific intercellular adhesion molecule‐3‐grabbing nonintegrin (DC‐SIGN), a C‐type lectin receptor, resulted in enhanced uptake of fluorescent Advax particles compared with mock‐transfected cells. Advax uptake was reduced with the addition of ethylenediaminetetraacetic acid and mannan to cells, which are known inhibitors of DC‐SIGN function. Finally, a specific blockade of DC‐SIGN using a neutralizing antibody abrogated Advax uptake in DC‐SIGN–expressing cells. Together, these results identify DC‐SIGN as a putative receptor for Advax. Given the known immunomodulatory role of DC‐SIGN, the findings described here have implications for the use of Advax adjuvants in humans and inform future mechanistic studies.

Funder

National Institutes of Health

National Health and Medical Research Council

Publisher

Wiley

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