A General Strategy toward Self‐assembled Nanovaccine Based on Cationic Lentinan to Induce Potent Humoral and Cellular Immune Responses

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2024-10, Vol.20 (43), p.e2402792-n/a
• Main Authors: Yu, Ruihong, Jin, Lan, Song, Zuchen, Jiao, Lina, Wang, Zheng, Zhou, Yantong, Ma, Yan, Guan, Sumei, Zhang, Zhimin, Wang, Deyun, Liu, Huina, Sun, Yuechao, Zhang, Shun, Cai, Ting, Sun, Haifeng, Qiu, Yawei, Miao, Jinfeng, Liu, Zhenguang
• Format: Article
• Language: English
• Subjects: Adjuvants; Animals; antigen delivery; Bone marrow; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Cations; Cations - chemistry; Cytokines; Dendritic Cells - drug effects; Dendritic Cells - immunology; immune responses; Immune system; Immunity, Cellular - drug effects; Immunity, Humoral - drug effects; Lentinan; Lentinan - chemistry; Lentinan - pharmacology; Lymphocytes; Melanoma, Experimental - immunology; Mice; Mice, Inbred C57BL; Nanoparticles - chemistry; Nanovaccines; Ovalbumin; Ovalbumin - immunology; Proteins; Receptors; Retinoic acid; Self-assembly; self‐assembled nanovaccines; targeted delivery; Tumor necrosis factor-TNF; Vaccines; Vaccines - immunology
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202402792

Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self‐assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self‐assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll‐like receptors 2/4 (TLR2/4) to produce effective antigen cross‐presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA‐specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid‐inducible gene I (RIG‐I) receptor, and cytokine‐cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)‐expressing B16 melanoma cell (B16‐OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self‐assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system. A self‐assembled nanovaccine (CLNTO nanovaccine) is prepared by cationic Lentinan and ovalbumin. CLNTO nanovaccine induces the uptake and maturation of bone marrow dendritic cells via the TLR2/4 receptor to produce effective antigen cross‐presentation. CLNTO nanovaccine has lymph node targeting and prolongs antigen release in the lymph nodes. Furthermore, CLNTO nanovaccine promote the interactions between T cells and B cells, and the generation of robust cellular and humoral immune responses.