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. 2023 May 17;20(10):1251–1253. doi: 10.1038/s41423-023-01024-x

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — A The table summarizes HA-based vaccines validated preclinically from 2015 to 2023. MPLA = the detoxified derivative of lipopolysaccharide (LPS) isolated from the gram-negative Salmonella Minnesota R595 bacterial strain; HBsAg = recombinant hepatitis B surface antigen; NPs = nanoparticles; DOTAP = 1,2-dioleoyl-3-trimethylammonium-propane; PEG = poly(ethylene glycol); poly I:C = polyinosinic-polycytidylic acid; CpG ODN = CpG oligodeoxynucleotides; NCs = nanocapsules; SBG = β-glucan schizophyllan; STING = stimulator of interferon genes; HPV = human papilloma virus. B Graphical summary of the HA mechanism of action. Following intramuscular administration, HA-bioconjugates rapidly enter draining lymph nodes due to their small size and ability to bind the LYVE-1 receptor without inducing any inflammatory response at the injection site. In the draining lymph nodes, the bioconjugate is retained longer than soluble antigens, and HA binding to TLRs and CD44 allows optimal interactions with APCs, inducing the maturation of these cells. Additionally, the repetitive display of multiple antigens bound to an HA chain facilitates the crosslinking of B-cell receptors (BCRs) and results in sustained activation of B cells. Created with BioRender.com