TAX and HBZ: hFc Ɣ 1 proteins as targets for passive immunotherapy

Document Type : Original Article

Authors

1 Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

4 Animal Laboratory, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Blood Borne Infections Research Center, Academic Center for Education, Culture, and Research (ACECR), Razavi Khorasan, Mashhad, Iran

Abstract

Objective(s): 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 Pichia pastoris. 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 vitro. 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. 

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 25, Issue 5
May 2022
Pages 586-596

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