AUTHOR=Gomes-Neto João F. , Sartorius Rossella , Canto Fábio B. , Almeida Thamyres S. , Dias André A. , Barbosa Carlos-Henrique D. , Melo Guilherme A. , Oliveira Ana Carolina , Aguiar Pedro-Henrique N. , Machado Carlos R. , de Matos Guedes Herbert L. , Santiago Marcelo F. , Nóbrega Alberto , De Berardinis Piergiuseppe , Bellio Maria 

TITLE=Vaccination With Recombinant Filamentous fd Phages Against Parasite Infection Requires TLR9 Expression

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01173

DOI=10.3389/fimmu.2018.01173

ISSN=1664-3224

ABSTRACT=<p>Recombinant filamentous <italic>fd</italic> bacteriophages (r<italic>fd</italic>) 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 r<italic>fd</italic> phages to protect against infection with the human protozoan <italic>Trypanosoma cruzi</italic>, the etiologic agent of Chagas Disease. For this, C57BL/6 (B6) and <italic>Tlr9<sup>−</sup></italic><sup>/</sup><italic><sup>−</sup></italic> mice were vaccinated with r<italic>fd</italic> phages expressing the OVA<sub>257–264</sub> peptide or the <italic>T. cruzi</italic>-immunodominant peptides PA8 and TSKB20 and challenged with either the <italic>T. cruzi</italic> Y-OVA or Y-strain, respectively. We found that vaccination with r<italic>fd</italic> phages induces anti-PA8 and anti-TSKB20 IgG production, expansion of Ag-specific IFN-γ, TNF-α, and Granzyme B-producing CD8<sup>+</sup> T cells, as well as <italic>in vivo</italic> Ag-specific cytotoxic responses. Moreover, the <italic>fd</italic>-TSKB20 vaccine was able to protect against mortality induced by a high-dose inoculum of the parasite. Although vaccination with r<italic>fd</italic> phages successfully reduced both parasitemia and parasite load in the myocardium of WT B6 mice, <italic>Tlr9<sup>−/−</sup></italic> animals were not protected against infection. Thus, our data extend previous studies, demonstrating that r<italic>fd</italic> phages induce Ag-specific IgG and CD8<sup>+</sup> T cell-mediated responses and confer protection against an important human parasite infection, through a TLR9-dependent mechanism.</p>