Vaccine nanodiscs plus polyICLC elicit robust CD8+ T cell responses in mice and non-human primates
| Autor: | Marisa E. Aikins, Kathryn E. Foulds, Yao Xu, Alireza Hassani Najafabadi, Dan H. Barouch, Emeka B. Okeke, David P. Adams, James J. Moon, Mitzi M. Donaldson, Jutaek Nam, Priyan Weerappuli, Andres M. Salazar, Robert A. Seder, Patrick A Lester, Zeynab Izadi Najaf Abadi, Taryn Hetrick, Wenmin Yuan, Anna Schwendeman |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Agonist
medicine.drug_class medicine.medical_treatment T cell Pharmaceutical Science Biology CD8-Positive T-Lymphocytes medicine.disease_cause Cancer Vaccines Article 03 medical and health sciences Mice 0302 clinical medicine Antigen Cancer immunotherapy Adjuvants Immunologic medicine Cytotoxic T cell Animals 030304 developmental biology 0303 health sciences Vaccines Synthetic Simian immunodeficiency virus Virology Macaca mulatta 3. Good health medicine.anatomical_structure Adjuvant CD8 030215 immunology |
| Zdroj: | J Control Release |
| Popis: | Conventional cancer vaccines based on soluble vaccines and traditional adjuvants have produced suboptimal therapeutic efficacy in clinical trials. Thus, there is an urgent need for vaccine technologies that can generate potent T cell responses with strong anti-tumor efficacy. We have previously reported the development of synthetic high-density protein (sHDL) nanodiscs for efficient lymph node (LN)-targeted co-delivery of antigen peptides and CpG oligonucleotides (a Toll-like receptor-9 agonist). Here, we performed a comparative study in mice and non-human primates (NHPs) to identify an ideal vaccine platform for induction of CD8+ T cell responses. In particular, we compare the efficacy of CpG class B, CpG class C, and polyICLC (a synthetic double-stranded RNA analog, a TLR-3 agonist), each formulated with antigen-carrying sHDL nanodiscs. Here, we report that sHDL-Ag admixed with polyICLC elicited robust Ag-specific CD8+ T cell responses in mice, and when used in combination with α-PD-1 immune checkpoint inhibitor, sHDL-Ag + polyICLC completely eliminated large established (~100 mm(3)) MC-38 tumors in mice. Moreover, sHDL-Gag + polyICLC induced robust Simian immunodeficiency virus Gag-specific, polyfunctional CD8+ T cell responses in rhesus macaques and could further amplify the efficacy of recombinant adenovirus-based vaccine. Notably, while both sHDL-Ag-CpG-B and sHDL-Ag-CpG-C generated strong Ag-specific CD8+ T cell responses in mice, their results were mixed in NHPs. Overall, sHDL combined with polyICLC offers a strong platform to induce CD8+ T cells for vaccine applications. |
| Databáze: | OpenAIRE |
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