https://ir.ymlib.yonsei.ac.kr/handle/22282913/168844 2026-06-17T14:07:51Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211761 Title: A transferable SARS-CoV-2 IRES module enables dual translation initiation for enhanced antigen expression in COVID-19 mRNA vaccines Authors: Seo, Han Young; Jung, Haewon; Lee, Se-Young; Jung, Hae-Gwang; Son, Yu-Min; Bak, Yeonju; Hwang, Seo-Yeon; Kim, Jung-Hee; Park, In Ho; Shin, Jeon-Soo; Oh, Jong-Won Abstract: mRNA vaccines are a versatile platform for infectious disease prevention and therapeutic applications, yet their performance is limited by exclusive reliance on cap-dependent translation, which is markedly suppressed under hypoxia and cellular stress. Here, we report a hybrid 5 ' untranslated region (5 ' UTR) that enables dual translation initiation via both cap-dependent and internal ribosome entry site (IRES) mechanisms. This element integrates a minimal stem-loop 4.5-5 module (SL4.5-5) from the SARS-CoV-2 genomic 5 ' UTR, in which a conserved 5 '-UUUCGU-3 ' motif within the SL5 loops is essential for function. Incorporating the SL4.5-5 module downstream of conventional 5 ' UTRs confers cap-independent translation capacity and enhances overall translation efficiency under translation-restrictive conditions such as hypoxia. When applied to the 5 ' UTRs of clinically validated COVID-19 vaccines, this module improves antigen expression in both modified and unmodified mRNAs. Notably, unmodified Omicron BA.5 and XBB.1.5 mRNA vaccines containing this element elicited potent humoral and cellular immune responses at sub-microgram doses, comparable to those induced by the approved N1-methylpseu-douridine-incorporated mRNA vaccine, raxtozinameran. These findings identify SL4.5-5 as a modular IRES element that enables dual translation initiation, promoting efficient protein synthesis under cap-dependent translation-restrictive conditions and expanding the functional landscape of mRNA vaccines and therapeutics beyond cap-dependent limitations. 2026-06-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/212477 Title: On-site loading of powder-attached microneedles enables quantitative and reproducible intradermal vaccine delivery Authors: Kim, Suwan; Kim, Hyemi; Kwon, Min-Ju; Ryu, Minwoo; Kim, Ji Seok; Baek, Seung-Ki; Kim, Chaiwon; Lee, Jae Myun; Kwak, Kihyuck; Park, Jung-Hwan Abstract: Conventional vaccination relies on liquid formulations that require cold-chain storage and administration by trained healthcare personnel, creating logistical barriers in resource-limited settings. Microneedle-based intradermal delivery enables solid vaccine administration; however, most microneedle vaccines are manufactured as pre-loaded products, limiting on-demand preparation and increasing operational and regulatory complexity. This study presents an on-site loaded powder-attached microneedle platform (On-site P-MNs), in which vaccine-free MNs bearing a silicone adhesive surface and solid OVA powders are supplied separately and combined immediately prior to administration. Lyophilized OVA formulations stabilized with trehalose were prepared, milled, and size-controlled to obtain powders suitable for reproducible attachment. A bead-assisted shaking process enabled practical on-site loading, and a portable air-blow step selectively removed weakly bound powder to improve loading uniformity and mechanical stability. Using identical microneedle geometry and the same powder batch, on-site loading achieved predictable protein content. Ex vivo porcine skin studies confirmed complete insertion and comparable OVA delivery efficiency between pre-loaded and On-site P-MNs. In a mouse immunization study, On-site P-MNs induced antigen-specific IgG responses comparable to those of Pre-loaded PMNs at the same nominal dose. Overall, On-site P-MNs provide a simple, portable strategy for on-demand intradermal delivery of solid vaccine formulations. 2026-06-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/212475 Title: A responder-informed gut microbial consortium enhances anti-PD-1 efficacy in a mouse cancer model Authors: Jeong, Uk Jin; Ali, Mohammed; Park, Yun Jee; You, Jin Sun; Yoon, Sang Sun Abstract: Aim: Immune checkpoint inhibitors (ICIs), particularly anti-programmed cell death protein 1 (PD-1) therapy, have improved cancer treatment outcomes, yet durable benefit is achieved in only a subset of patients. Growing evidence implicates the gut microbiome as a modulator of ICI responsiveness, but defined and experimentally validated microbial strategies remain limited. This study aimed to identify responder-associated gut microbes and to evaluate a defined bacterial consortium for enhancing PD-1 blockade efficacy. Methods: Publicly available shotgun metagenomic datasets from anti-PD-1-treated cancer patients were re-analyzed to compare gut microbiome profiles between responders and non-responders. Bacterial taxa reproducibly enriched in responders were selected based on consistency across analytical criteria and cultivability and assembled into a four-strain consortium (UJ-04). The immune-adjuvant potential of UJ-04, alone or combined with anti-PD-1 therapy, was evaluated in a B16-F10 melanoma mouse model, with tumor growth and immune responses assessed by flow cytometry. Results: Metagenomic re-analysis identified four commensal bacterial taxa consistently enriched in responder patients, forming the defined UJ-04 consortium. While UJ-04 alone showed minimal antitumor activity, combination treatment with anti-PD-1 significantly enhanced tumor growth inhibition compared with anti-PD-1 monotherapy. This effect was accompanied by increased intratumoral CD8+T cells and natural killer cells, with concordant immune trends in peripheral compartments. Conclusion: A responder-informed, defined microbial consortium functionally translates clinical microbiome associations into in vivo validation and enhances PD-1 blockade efficacy by modulating host antitumor immunity. These findings support defined bacterial consortia as microbiome-based immunomodulatory adjuncts for immunotherapy. 2026-06-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/212570 Title: Enhanced tuberculosis control via leveraging dendritic cell-mediated Th1 responses in preventive and immunotherapeutic vaccine strategies Authors: Kim, Hongmin; Kim, Jong-Seok; Kwon, Kee Woong; Kim, Woo Sik; Park, Minchul; Ha, Sang-Jun; Choi, Sangwon; Kim, Jiseon; Shin, Sung Jae Abstract: Introduction: Insufficient vaccine efficacy of the Bacillus Calmette-Gu & eacute;rin (BCG) and long, expensive tuberculosis (TB) treatments highlight the need for better TB control measures. Methods: This study evaluated whether the adoptive transfer of dendritic cell (DC)-based vaccines pulsed with culture filtrate antigens (CFA) of Mycobacterium tuberculosis (Mtb) could enhance BCG efficacy and support anti-TB drug therapy. Results: In BCG-vaccinated mice, adoptive transfer of CFA-pulsed DCs promoted swift T cell recruitment to the lung parenchyma, reducing bacterial load within 1 week post-infection, promoting the generation of tissue-resident T cells and expansion of CD4* T cells co-producing IFN-c, IL-2, and/or TNF-a. The vaccine efficacy persisted for a prolonged period post-infection, with protection found in both high dose and low dose Mtb infection models. Additionally, CFA-DC administration during chemotherapy enhanced treatment efficacy, maintaining CD4' ' T cell responses. In latent TB models, mice were protected from Mtb reactivation in both drug-sensitive , multidrug-resistant TB models. Conclusions: DC-based prophylactic and immunotherapeutic vaccine strategies enhance protective immunity during BCG vaccination and chemotherapy, offering new insights into TB control strategies. (c) 2025 The Author(s). Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 2026-05-01T00:00:00Z