Selective APC-targeting of a novel Fc-fusion multi-immunodominant recombinant protein (tTax-tEnv:mFcγ2a) for HTLV-1 vaccine development

• Published in: Life sciences (1973) 2022-11, Vol.308, p.120920-120920, Article 120920
• Main Authors: Shafifar, Mina, Mozhgani, Sayed-Hamidreza, Razavi Pashabayg, Kobra, Mosavat, Arman, Karbalaei, Mohsen, Norouzi, Mehdi, Rezaee, Seyed Abdolrahim
• Format: Article
• Language: English
• Subjects: ATLL; Fc-fusion vaccine; HAM/TSP; HTLV-1; Recombinant protein; Subunit vaccine
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120920

HTLV-1 causes two life-threatening diseases: adult T-cell leukaemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. Due to the lack of proper treatment, an effective HTLV-1 vaccine is urgently needed. DNA sequences of 11–19 and 178–186 amino acids of HTLV-1-Tax and SP2 and P21 were fused to the mouse-Fcγ2a, or His-tag called tTax-tEnv:mFcγ2a and tTax-tEnv:His, respectively. These constructs were produced in Pichia pastoris, and their immunogenicity and protective properties were assessed in a mouse challenging model with an HTLV-1-MT2 cell line. The immunogenicity assessments showed significant increase in IFN-γ production in animals receiving tTax-tEnv:mFcγ2a (1537.2 ± 292.83 pg/mL) compared to tTax-tEnv:His (120.28 ± 23.9, p = 0.02). IL-12 production also increased in group receiving tTax-tEnv:mFcγ2a than tTax-tEnv:His group, (23 ± 2.6 vs 1.5 ± 0.6, p = 0.01), respectively. The IFN-γ and IL-12 levels in the Fc-immunised group were negatively correlated with PVL (R = -0.82, p