Development of surface engineered antigenic exosomes as vaccines

Exosomes secreted by antigen presenting cells (APCs) can elicit immune responses by carrying major histocompatibility complex (MHC) class I molecules complexed with antigenic peptides and other co-stimulating factors. Researchers at Iowa State University have developed novel immunomagnetic nanographene particles to sequentially isolate, surface engineer, and release intact dendritic cell (DC) exosomes for use as a potential vaccine platform against respiratory syncytial virus (RSV) . The H-2Db-restricted, immunodominant peptides from RSV (M187–195 and NS161–75) were introduced to MHC-I on DC-derived exosomes to express peptide/MHC-I (pMHC-I) complexes. A mouse model of RSV infection was used to define the immunogenicity of surface engineered exosomes for activating virus-specific immune responses. Ex vivo assays demonstrated that engineered exosomes carrying RSV-specific peptides can elicit interferon-gamma (IFN-γ) production by virus-specific CD8+ T cells isolated from RSV-infected C57BL/6 mice. In vivo assays demonstrated that subcutaneous administration of both M187–195 and NS161–75 engineered exosomes to mice, with or without additional adjuvant, appeared safe and well tolerated, however, did not prime antigen-specific CD8+ T cell responses. Surface engineered exosomes are immunogenic and promising for further development as a vaccine platform.

Engineered exosomes were immunogenic for activating RSV-specific CD8 T cells ex vivo

Figure 2

(A) Schematic illustration of the establishment of a DC-CD8 T cell co-culture model. C57BL/6J mice were infected intranasally with RSV strain A2 to generate RSV-specific CD8+ T cells. Magnetic-activated cell sorting (MACS) was used to sort CD8+ T cells from RSV-infected mice and CD11c + DCs from non-infected mice. CD8+ T cells and CD11c + DCs (5:3 ratio) were incubated for 72 h with escalating concentrations (5 μL, 10 μL, 25 μL) of exosomes engineered with M187–195 or NS161–75 peptides with or without LPS (100 ng/mL). (BC) Cell culture supernatants were collected on day 3 of stimulation with M187–195 or NS161–75 engineered exosomes. The samples were diluted 1:4 and analyzed by commercial ELISA for IFN-γ. Data represent means ± SEM. ****p < 0.0001 as determined by one-way ANOVA and Dunnett’s multiple comparisons test. *p < 0.05 as determined by two-way ANOVA and Šídák’s multiple comparisons test.

Hong S, Ruan S, Greenberg Z, He M, McGill JL. (2021) Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus. Sci Rep 11, 21358. [article]

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