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oai:figshare.com:article/34038018 2026-10-01T04:05:22Z category_7 category_12 category_21 category_46 category_811 category_64 category_135 portal_63 item_type_6 month_year_10_2026

An NIR-II-Traceable Nanovaccine Programs Systemic Antigen Residence to Establish Checkpoint-Responsive Progenitor-Exhausted CD8-Positive T‑Cell Reservoirs for Effective Cancer Immunotherapy Muye Ma (17674482) Shiqiang Xie (25151526) Han Zhang (110653) Haoran Ma (1732840) Tao Wang (12008) Xinyue Wang (286629) Zhihao Zhao (7284848) Huize Han (10977606) Yongliang Zhang (122202) Jianjun He (104318) Rui Tian (635672) Wei Tang (53470) Medicine Cell Biology Biotechnology Immunology Mathematical Sciences not elsewhere classified Cancer Computational Biology upon programmed death sup >+</ sup polyethylene glycol 2000 lymphoid signals peaking improved melanoma control immune niches antigens engineerable biomaterial parameter traceable nanovaccine strategy dendritic cell maturation tumor immune remodeling nirvax also accumulates ii )- traceable ‑ cell reservoirs tumor microenvironment residence nanovaccine hematopoietic remodeling cell responses cell generation cell fate vivo </ tme ). sustain checkpoint specific progenitor slos ), second near responsive progenitor responsive immunity report nirvax ova ). limited capacity ligand 1 intravenous administration infrared window gradual clearance establish checkpoint epitope spreading distearoyl phosphoethanolamine covalent conjugation couples real biased differentiation Nanovaccines offer an opportunity to define where, how long, and in which immune niches antigens are presented. However, many cancer vaccine systems still preferentially induce transient effector CD8⁺ T-cell responses with limited capacity to sustain checkpoint-responsive immunity. Here, we report NIRVax, a second near-infrared window (NIR-II)-traceable, long-residence nanovaccine that couples real-time <i>in vivo</i> tracking to programmable systemic antigen residence. NIRVax is assembled from a triphenylamine-based NIR-II fluorophore and distearoyl phosphoethanolamine-polyethylene glycol 2000 (DSPE-PEG₂₀₀₀), followed by covalent conjugation of the model protein antigen ovalbumin (OVA). After intravenous administration, NIRVax sustains antigen residence across secondary lymphoid organs (SLOs), with lymphoid signals peaking at day 4 postinjection followed by gradual clearance. This material residence profile enhances antigen uptake, dendritic cell maturation, and stem-like CD8⁺ T-cell generation. NIRVax also accumulates at bone-associated sites, where it is associated with hematopoietic remodeling, myeloid-biased differentiation, and a reduced suppressive myeloid output. Functionally, systemic NIRVax vaccination establishes antigen-specific progenitor-exhausted CD8⁺ T-cell (T_PEX) reservoirs across lymphoid tissues and the tumor microenvironment (TME). Upon programmed death-ligand 1 (PD-L1) blockade, these reservoirs are mobilized into effector CD8⁺ T-cell responses, leading to tumor immune remodeling, epitope spreading, and improved melanoma control. These findings establish spatiotemporal antigen residence as an engineerable biomaterial parameter for shaping the CD8⁺ T-cell fate and provide a NIR-II-traceable nanovaccine strategy for potentiating checkpoint cancer immunotherapy. 2026-10-01T00:00:00Z Text Journal contribution 10.1021/acsnano.6c12073.s001 https://figshare.com/articles/journal_contribution/An_NIR-II-Traceable_Nanovaccine_Programs_Systemic_Antigen_Residence_to_Establish_Checkpoint-Responsive_Progenitor-Exhausted_CD8-Positive_T_Cell_Reservoirs_for_Effective_Cancer_Immunotherapy/34038018 CC BY-NC 4.0