Exosome co-delivery of a STING agonist augments immunogenicity elicited by CVB3 VP1 vaccine via promoting antigen cross-presentation of CD8+DCs
Exosome co-delivery of a STING agonist augments immunogenicity elicited by CVB3 VP1 vaccine via promoting antigen cross-presentation of CD8+DCs
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DOI：
10.1016/j.ijbiomac.2024.129518
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发表时间：
2024-01-28
影响因子：
8.2
通讯作者：
Yue，Yan
中科院分区：
文献类型：
--
作者：
Zhang，Changwei;Cao，Qinghui;Yue，Yan
The induction of a robust CD8+T cell response is critical for the success of an antiviral vaccine. In this study, we incorporated a STING agonist (SA) 2′3’-cGAMP into a previously developed exosome-based CVB3 viral myocarditis vaccine (Exo-VP1) to enhance its ability to induce CD8+T cell responses and immunoprotection. Our results showed that compared to free SA adjuvant, exosome-mediated co-delivery (ExoSA-VP1) significantly enhanced SA uptake by dendritic cells (DCs) and more potently stimulated DC maturation. Immunization of mice showed that the ExoSA-VP1 vaccine-induced higher levels of CVB3-specific T cell proliferation and cytotoxicity, significantly increased the percentage of IFN-γ+CD8+rather than CD4+T cells, effectively reduced cardiac viral loads, attenuated myocarditis and improved survival in mice compared to the previous Exo-VP1 vaccine. Further investigation showed that ExoSA-VP1 significantly increased both the percentage and antigen cross-presentation capacity of splenic CD8+DCs. Depletion of these CD8+DCs by cytochrome C administration nearly abolished the advantage of ExoSA-VP1 in dominantly inducing IFN-γ+CD8+cytotoxic T lymphocyte (CTL) production in immunized mice. Taken together, our results demonstrated the potential of ExoSA-VP1 as a promising candidate for anti-CVB3 vaccines and provide insights into immune-enhancing strategies aiming at augmenting antigen cross-presentation by DCs and enhancing potent CTL responses.
