Abstract
Recombinant filamentous fd bacteriophages (rfd) expressing antigenic peptides were shown to induce cell-mediated immune responses in the absence of added adjuvant, being a promising delivery system for vaccination. Here, we tested the capacity of rfd phages to protect against infection with the human protozoan Trypanosoma cruzi, the etiologic agent of Chagas Disease. For this, C57BL/6 (B6) and Tlr9−/− mice were vaccinated with rfd phages expressing the OVA257–264 peptide or the T. cruzi-immunodominant peptides PA8 and TSKB20 and challenged with either the T. cruzi Y-OVA or Y-strain, respectively. We found that vaccination with rfd phages induces anti-PA8 and anti-TSKB20 IgG production, expansion of Ag-specific IFN-γ, TNF-α, and Granzyme B-producing CD8+ T cells, as well as in vivo Ag-specific cytotoxic responses. Moreover, the fd-TSKB20 vaccine was able to protect against mortality induced by a high-dose inoculum of the parasite. Although vaccination with rfd phages successfully reduced both parasitemia and parasite load in the myocardium of WT B6 mice, Tlr9−/− animals were not protected against infection. Thus, our data extend previous studies, demonstrating that rfd phages induce Ag-specific IgG and CD8+ T cell-mediated responses and confer protection against an important human parasite infection, through a TLR9-dependent mechanism.
Highlights
Filamentous fd bacteriophages are non-lytic viruses that infect and replicate only in host bacteria and, have been considered safe for the vertebrate host so far
Previous studies have shown that antigen peptides expressed on the phage capsid can be displayed through MHC class I and class II pathways on antigen-presenting cells (APCs), resulting in the capacity of inducing immune responses mediated by specific antibodies fd-Bacteriophage Vaccine Against Parasite Infection and by helper and cytotoxic T lymphocytes [2, 3]
It has been previously shown that recombinant fd phages, expressing a CD8 epitope and directed to CD205+ dendritic cells (DCs), are potent inducers of Ag-specific CTL responses and are more effective than other immunization strategies for inhibiting the growth of the B16 tumor in vivo [1], reviewed in Ref. [24]
Summary
Filamentous fd bacteriophages are non-lytic viruses that infect and replicate only in host bacteria and, have been considered safe for the vertebrate host so far. Previous studies have shown that antigen peptides expressed on the phage capsid can be displayed through MHC class I and class II pathways on antigen-presenting cells (APCs), resulting in the capacity of inducing immune responses mediated by specific antibodies fd-Bacteriophage Vaccine Against Parasite Infection and by helper and cytotoxic T lymphocytes [2, 3]. A single-chain antibody fragment (scFv), able to target dendritic cells (DCs) through the endocytic receptor DEC-205 ( known as CD205), can be introduced at the N-terminus of the pIII protein, further improving phage-uptake by DCs and their maturation These fdsc-αDEC particles were shown to induced a strong and sustained CD8+ T cell-mediated anti-tumor response [1]. The present work extends previous studies on the immunogenicity mechanisms mediated by fd phages, reinforcing the potential use of these particles as a valuable delivery system for immunization without the need of exogenous adjuvant administration and shows, for the first time, its promising use in vaccination against intracellular parasites
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