Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 31, Issue 41, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202105059
Keywords
cancer; cytotoxic T lymphocytes; immunotherapy; nanoparticles; SARS-CoV-2
Categories
Funding
- Natural Science Foundation of Shandong Province [ZR2020QB165]
- National Natural Science Foundation of China [22007058]
- Natural Science Foundation of Jiangsu Province [BK20200236]
- State Key Laboratory of Microbial Technology Open Projects Fund [M2020-02]
- Central Government Guide Local Science and Technology Development Funds [YDZX20203700002579]
- National Institute of Allergy and Infectious Diseases [R01AI146210]
- National Cancer Institute [R01 CA225105]
- Qilu Young Scholar Fund of Shandong University
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Cytotoxic T-lymphocytes (CTLs) play a central role in protective immunity against malignancies and infectious diseases. This study developed partially oxidized acetalated dextran nanoparticles (Ox-AcDEX NPs) as a general vaccine delivery platform. By conjugating CTL peptide epitopes and immune-enhancing adjuvants, effective vaccines against cancer and viruses were successfully created, demonstrating the potential for immune protection.
Cytotoxic T-lymphocytes (CTLs) are central for eliciting protective immunity against malignancies and infectious diseases. Here, for the first time, partially oxidized acetalated dextran nanoparticles (Ox-AcDEX NPs) with an average diameter of 100 nm are fabricated as a general platform for vaccine delivery. To develop effective anticancer vaccines, Ox-AcDEX NPs are conjugated with a representative CTL peptide epitope (CTLp) from human mucin-1 (MUC1) with the sequence of TSAPDTRPAP (referred to as Mp1) and an immune-enhancing adjuvant R837 (referred to as R) via imine bond formation affording AcDEX-(imine)-Mp1-R NPs. Administration of AcDEX-(imine)-Mp1-R NPs results in robust and long-lasting anti-MUC1 CTL immune responses, which provides mice with superior protection from the tumor. To verify its universality, this nanoplatform is also exploited to deliver epitopes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to prevent coronavirus disease 2019 (COVID-19). By conjugating Ox-AcDEX NPs with the potential CTL epitope of SARS-CoV-2 (referred to as Sp) and R837, AcDEX-(imine)-Sp-R NPs are fabricated for anti-SARS-CoV-2 vaccine candidates. Several epitopes potentially contributing to the induction of potent and protective anti-SARS-CoV-2 CTL responses are examined and discussed. Collectively, these findings shed light on the universal use of Ox-AcDEX NPs to deliver both tumor-associated and virus-associated epitopes.
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