Siglec-1-targeting single domain antibodies block or enhance pathogen binding to dendritic cells.

Authors

Hendrik J Brink, Alsya J Affandi, Shirley Man, Noah C C T Dekker, Enno A Großewichtrup, Rianne G Bouma, Negisa Seyed Toutounchi, Veronique A L Konijn, Joeke G C Stolwijk, John L van Hamme, Katarzyna Olesek, Dijmphna A M Heijnen, Alexander Fish, Angeliki Moutsiopoulou, Patrick H N Celie, Gillian Dekkers, Raimond Heukers, Enrico Mastrobattista, Martine J Smit, Yvette van Kooyk, Marit J van Gils, Astrid P Heikema, Neeltje A Kootstra, Teunis B H Geijtenbeek, Joke M M den Haan

Published in

The Journal of biological chemistry. Pages 113542. Sep 08, 2026. Epub Sep 08, 2026.

Abstract

Siglec-1 (Sialoadhesin/CD169), expressed on myeloid cells, is a receptor for sialic acids that mediates adhesion to host cells and pathogens. However, certain pathogens exploit Siglec-1 binding for further dissemination and interfering with this binding may serve as potential therapeutic interventions. Here we identified high-affinity single domain antibodies, (also known as VHHs or Nanobodies) that allo- or orthosterically modulate ligand binding of Siglec-1. VHH clone 2C2 bound directly to the ligand binding site of Siglec-1 and effectively blocked binding of a diverse set of ligands, such as ganglioside liposomes, Campylobacter jejuni, and SARS-CoV-2, to monocyte-derived dendritic cells (moDCs) and ex vivo Siglec-1⁺ DCs. In contrast, VHH 1B5 and 1C1 bound outside of the ligand binding site and enhanced Siglec-1 interactions with ganglioside liposomes and Campylobacter jejuni. Mechanistically, VHH 1B5 and 1C1 appear to interfere with the cis-binding sialic acids present on the Siglec-1-expressing cell surface, thereby facilitating increased trans-interactions with ligands. In conclusion, we have isolated VHH that bind to different sites on Siglec-1 and thereby enhance or block ligand binding to a variety of sialylated pathogens. Moreover, unlike conventional blocking antibodies targeting specific pathogens, Siglec-1 binding VHH may serve as broad-spectrum pathogen blocking agents.

PMID:
42710659
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.