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Functionalized aluminum hydroxide-based self-adjuvanted nanovaccine orchestrates antitumor immune responses via Dectin-1 signaling. | LitMetric

Functionalized aluminum hydroxide-based self-adjuvanted nanovaccine orchestrates antitumor immune responses via Dectin-1 signaling.

J Control Release

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Centre for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:

Published: December 2024

AI Article Synopsis

Article Abstract

Self-adjuvanted vaccine delivery platforms possess potential for targeted delivery of antigens and initiation of potent immune responses. Although aluminum-containing adjuvants have been approved and widely used in human vaccines, their effectiveness in inducing Th1-type immune responses is far from satisfactory. To facilitate antigen delivery and activate potent antitumor immune responses, a self-adjuvanted nanovaccine (CPBG-Al@OVA) is constructed by functionalizing aluminum hydroxide with β-1,3-glucan, which recognizes pattern recognition receptors via Dectin-1. Carboxymethyl-phosphorylated β-1,3-glucan (CPBG) has been synthesized and optimized to achieve superior adjuvanticity while maintaining water solubility. CPBG then self-assembles with aluminum hydroxide and the targeted antigen, leading to the formation of a nanovaccine CPBG-Al@OVA. Owing to the favorable nanoscale size distribution, CPBG-Al@OVA effectively drains to the lymph nodes and is internalized by antigen-presenting cells (APCs) through Dectin-1-mediated endocytosis, activating the Syk and Raf1 signaling pathways and leading to upregulated TNFSF15 and OX40L expression to activate APCs. Following immunization, CPBG-Al@OVA activates potent CD8 T cell and humoral responses to inhibit tumor growth. Notably, mice vaccinated with CPBG-Al@OVA showed extended survival, with more than 70 % of the mice surviving for over 50 days post-tumor challenge. Moreover, the CPBG-Al nanoparticle also possesses personalized immune-activating capacity by encapsulating tumor lysate as an antigen, specifically suppressing tumor growth. This strategy synergizes the adjuvant effects of aluminum and β-1,3-glucan, offering a platform for self-adjuvanted nanovaccine design with significant clinical translational potential.

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Source
http://dx.doi.org/10.1016/j.jconrel.2024.12.035DOI Listing

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