TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display

Abstract

Although the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects lepidopteran invertebrates as natural hosts, represents an efficient vector for vaccine development. Baculovirus surface display induces strong humoral responses against viruses and parasites. A novel strategy based on capsid display carrying foreign antigens in the AcMNPV particle further improved the immune response by eliciting CD8+ T cell activation. In this study, we analyze the intracellular mechanisms and signalling pathways involved in CD8+ T cell activation by capsid display. Our results show that baculovirus can attach to the cell surface, enter dendritic cells (DCs), transit within endocytic vesicles and escape to the cytosol for further degradation by the proteasome. We found that the availability of viral proteins, endosomal acidification, and proteasome activity are needed for efficient Major Histocompatibility Complex class‐I presentation by baculovirus carrying Ovalbumin in the viral capsid. Importantly, we demonstrated with this strategy that the induction of cytotoxic T cells and IL‐12 production by DCs are TLR9‐dependent and STING‐independent. Finally, our study shows differential intracellular processing for capsid and surface baculovirus proteins in DCs and highlights the role of different danger receptors during cytotoxic T cell priming through the capsid display delivery system, which could lead to improved baculovirus‐based vaccines development.

Epstein-Barr virus suppresses N6-methyladenosine modification of TLR9 to promote immune evasion

“…Molinari et al. revealed that Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) carrying a fragment of OVA (chicken egg ovalbumin) fused to the N terminus of VP39 protein (BV-cOVA) triggers endosomal TLR9 signaling in DCs, which triggers a CD8 + T cell-mediated adaptive immune response through the TLR9/MyD88 pathway ( 80 ). We identified that STM2457 treatment in the cocultured cell systems can inhibit the expression levels of CD107a + and IFN-γ + in CD8 + T and CD4 + T cells upon CpG-ODN stimulation.…”

Vaccination with parasite-specific TcTASV proteins combined with recombinant baculovirus as a delivery platform protects against acute and chronic Trypanosoma cruzi infection

“…Presentation of the antigen at the capsid or envelope surface of recombinant BV is crucial because differential immune responses are triggered (Tavarone et al, 2017). In particular, we have previously demonstrated that the expression and presentation of a model antigen at the BV capsid promotes strong cellular responses, along with a specific IFNɣ production by cytotoxic CD8+ lymphocytes (Molinari et al, 2011(Molinari et al, , 2022.…”

Vaccine against Trypanosoma cruzi infection using the Parasite Antigen TcTASV Displayed at Baculovirus Capsid

“…In particular, we have previously demonstrated that the expression and presentation of a model antigen at the BV capsid promotes strong cellular responses, along with a specific IFNɣ production by cytotoxic CD8+ lymphocytes 25,26 .…”