Recombinant GPEHT Fusion Protein Derived from HTLV-1 Proteins with Alum Adjuvant Induces a High Immune Response in Mice

• Authors: Hamid Jahantigh, Emory University; Angela Stufano, University of Bari; Farhad Koohpeyma, Shiraz University of Medical Sciences; Vajihe Sadat Nikbin, Pasteur Institute of Iran; Zahra Shahosseini, Iran University of Medical Sciences; Piero Lovreglio, University of Bari
• Journal Title: VACCINES
• Volume: Volume 11, Number 1
• Publisher: MDPI | 2023-01-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/vaccines11010115
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Medicine, Research & Experimental; Research & Experimental Medicine; HTLV-1; HAM; TSP; reverse vaccinology; multi-epitope vaccine; recombinant protein; T-CELLS; B-CELL; VIRUS; TAX; VACCINE; TUMORIGENESIS; TRANSMISSION; INFECTION; EPITOPE

Abstract

The human T-cell leukemia virus type 1 (HTLV-1) is a positive single-stranded RNA virus that belongs to the delta retrovirus family. As a result, a vaccine candidate that can be recognized by B cells and T cells is a good candidate for generating a durable immune response. Further, the GPEHT protein is a multi-epitope protein designed based on the Gag, Pol, Env, Hbz, and Tax proteins of HTLV-1. In developing a suitable and effective vaccine against HTLV-1, the selection of a designed protein (GPEHT) with the formulation of an alum adjuvant was conducted. In this study, we assessed the potential of a multi-epitope vaccine candidate for stimulating the immune response against HTLV-1. In assessing the type of stimulated immune reaction, total IgG, IgG1, and IgG2a isotypes, as well as the cytokines associated with Th1 (IFN-γ), Th2 (IL-4), and Th17 (IL-17), were analyzed. The outcomes showed that the particular antisera (total IgG) were more elevated in mice that received the GPEHT protein with the alum adjuvant than those in the PBS+Alum control. A subcutaneous vaccination with our chimera protein promoted high levels of IgG1 and IgG2a isotypes. Additionally, IFN-γ, IL-4, and IL-17 levels were significantly increased after spleen cell stimulation in mice that received the GPEHT protein. The immunogenic analyses revealed that the GPEHT vaccine candidate could generate humoral and cell-mediated immune reactions. Ultimately, this study suggests that GPEHT proteins developed with an alum adjuvant can soon be considered as a prospective vaccine to more accurately evaluate their protective efficacy against HTLV-1.