Efficient Induction of HTLV-1-Specific CTL Response by HTLV-1/HBc Chimeric Particle without Adjuvant as a Prophylactic for HTLV-1- Associated T-Cell Leukemia
Authors: Kozako Tomohiro , Fukada Katsuhiko , Hirata Shinya , Harao Michiko , Nishimura Yasuharu , Kino Youichiro , White Yohann , Arima Naomichi 
Published: October 2019

Abstract
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm that develops only after long-term chronic infection with human T-cell leukemia virus-1 (HTLV-1). HTLV-1-specific Cytotoxic T lymphocytes (CTL) play an important role in suppressing proliferation of HTLV-1-infected or transformed T cells in vitro. The development of ATLL in approximately 2% of persons chronically infected with HTLV-1 may suggest a specific immunegenetic background predisposing to CTL failure in a proportion of HTLV-1 carriers. On the other hand, virus like particle is demonstrated to induce stronger humoral, T helper and cytotoxic T-cell responses without adjuvant. As free synthetic peptides or proteins are usually poor immunogens, the hepatitis B core (HBc) particle is a potential target carrier protein to induce immunity without use of an adjuvant. In this study, we examined the efficient induction of HTLV-1-specific CD8+ T-cell response by HTLV-1/HBc chimeric particles inserting HLA-A*0201-restricted HTLV-1 Tax-epitope without adjuvant (Figure 1). The immunization of HLA-A*0201 transgenic mice with the chimeric particle induced antigen-specific IFN-□ reaction by ELISPOT assay, whereas epitope peptide only induced no reaction (Figure 2). HTLV-1/HLA tetramer assay detected induction of HTLV-1-specific CD8+ T-cells in both splenic and inguinal lymph node cells by HTLV-1/HBc chimera particles. Furthermore, upon exposure of these dendritic cells (DCs) to the chimeric particles, the expression of CD86 was increased in a dose-dependent manner. These results suggest that HTLV-1/HBc chimeric particles are capable of inducing strong cellular immune responses without adjuvant via effective maturation of DCs and are potentially useful as an effective vaccine carrier for the treatment of cancers and infectious diseases by varying the epitope peptide.
Figure 1. Electronmicrographs of recombinant HTLV-1 Tax/HBc chimeric particles. Figure 1. Electronmicrographs of recombinant HTLV-1 Tax/HBc chimeric particles. Figure 2. Induction of cellular immunity by intradermal immunization with HTLV-1/HBc chimeric particle. Mice were immunized twice with recombinant HTLV-1/HBc chimeric particle, HTLV-1 peptide and HTLV-1 peptide + HBc particle. The number of IFN-□-producing cells was measured by ELISPOT assay. IFN-□ spots show the number of peptide-loaded target cells to peptide-unloaded target cells. *P<0.05, **P<0.01 vs PBS group. The experiments were performed in triplicate. Mean S.E. are shown in the results. Figure 2. Induction of cellular immunity by intradermal immunization with HTLV-1/HBc chimeric particle. Mice were immunized twice with recombinant HTLV-1/HBc chimeric particle, HTLV-1 peptide and HTLV-1 peptide + HBc particle. The number of IFN-□-producing cells was measured by ELISPOT assay. IFN-□ spots show the number of peptide-loaded target cells to peptide-unloaded target cells. *P<0.05, **P<0.01 vs PBS group. The experiments were performed in triplicate. Mean S.E. are shown in the results.