Exosome co-delivery of a STING agonist augments immunogenicity elicited by CVB3 VP1 vaccine via promoting antigen cross-presentation of CD8 + DCs.
Int J Biol Macromol
; 261(Pt 1): 129518, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38244740
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vacinas Virais
/
Exossomos
/
Miocardite
Limite:
Animals
Idioma:
En
Revista:
Int J Biol Macromol
Ano de publicação:
2024
Tipo de documento:
Article