TAX and HBZ: HFc Ɣ 1 Proteins As Targets for Passive Immunotherapy
Overview
Authors
Affiliations
Objectives: Human T leukemia virus type one (HTLV-1) causes two life-threatening diseases in around five percent of infected subjects, a T cell malignancy and a neurodegenerative disease. TAX and HBZ are the main virulence agents implicated in the manifestation of HTLV-1-associated diseases. Therefore, this study aims to produce these HTLV-1 factors as recombinant Fc fusion proteins to study the structures, their immunogenic properties as vaccines, and their capability to produce specific neutralization antibodies.
Materials And Methods: TAX and HBZ sequences were chosen from the NCBI-nucleotide database, then designed as human Fc chimers and cloned into . Produced proteins were purified by HiTrap affinity chromatography and subcutaneously injected into rabbits. Rabbit Abs were purified by batch chromatography, and their neutralization activities for the HTLV-1-infected MT-2 cell line were assessed. Furthermore, the protective abilities of recombinant proteins were evaluated in Tax or HBZ immunized rabbits by MT-2 cell line inoculation and measurement of HTLV-1-proviral load.
Results: Specific Abs against Tax and HBZ can eliminate 2 million MT-2 cells in 1/1000 dilution . In challenging assays, the immunization of the animals using Tax or HBZ had no protective activity as HTLV-1 PVL was still positive.
Conclusion: The result suggests that recombinant TAX and HBZ: hFcγ1 proteins can produce a proper humoral immune response. Therefore, they could be considered a passive immunotherapy source for HTLV-1-associated diseases, while total TAX and HBZ proteins are unsuitable as HTLV-1 vaccine candidates.
Ahmadi Ghezeldasht S, Momen Heravi M, Valizadeh N, Rafatpanah H, Shamsian S, Mosavat A Appl Biochem Biotechnol. 2022; 195(3):1862-1876.
PMID: 36399306 PMC: 9673214. DOI: 10.1007/s12010-022-04259-y.