Exosomes as Potent Cell-Free Peptide-Based Vaccine. II. Exosomes in CpG Adjuvants Efficiently Prime Naive Tc1 Lymphocytes Leading to Tumor Rejection

TLDR

Vaccines should be stable, safe, defined, and readily available reagents that elicit robust effector and memory antigen‑specific T‑cell responses, and dendritic‑cell‑derived exosomes, carrying discrete protein sets and functional MHC I/II molecules, meet these criteria and have shown safety in early phase I trials. This study demonstrates that Toll‑like receptor 3 and 9 ligands serve as effective adjuvants to prime MHC‑restricted CD8⁺ T‑cell responses when combined with exosomes. The authors combine clinically available TLR3/9 ligands with exosomes, leveraging the exosomes’ MHC presentation capability to activate CD8⁺ T cells in vivo. Human exosomes mixed with CpG oligonucleotides induced strong anti‑melanoma immunity in HLA‑A2 transgenic mice, confirming CpG as ideal adjuvants for exosome‑based cancer vaccines.

Abstract

Abstract Ideal vaccines should be stable, safe, molecularly defined, and out-of-shelf reagents efficient at triggering effector and memory Ag-specific T cell-based immune responses. Dendritic cell-derived exosomes could be considered as novel peptide-based vaccines because exosomes harbor a discrete set of proteins, bear functional MHC class I and II molecules that can be loaded with synthetic peptides of choice, and are stable reagents that were safely used in pioneering phase I studies. However, we showed in part I that exosomes are efficient to promote primary MHC class I-restricted effector CD8+ T cell responses only when transferred onto mature DC in vivo. In this work, we bring evidence that among the clinically available reagents, Toll-like receptor 3 and 9 ligands are elective adjuvants capable of triggering efficient MHC-restricted CD8+ T cell responses when combined to exosomes. Exosome immunogenicity across species allowed to verify the efficacy of good manufactory procedures-manufactured human exosomes admixed with CpG oligonucleotides in prophylactic and therapeutic settings of melanoma in HLA-A2 transgenic mice. CpG adjuvants appear to be ideal adjuvants for exosome-based cancer vaccines.