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

Shafifar, Mina; Mozhgani, Sayed‐Hamidreza; Pashabeyg, Kobra Razavi; Mosavat, Arman; Keikha, Masoud; Norouzi, Mehdi; Rezaee, Seyed Abdolrahim

doi:10.1016/j.lfs.2022.120920

Cited by 10 publications

(13 citation statements)

References 53 publications

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“…Additionally, generating a single-epitope peptide vaccine against HTLV-1 might result in inadequate immune reactions. Thus, based on our previous report and unlike the previous candidate vaccine, which relied on a portion of the HTLV-1 genome, in this work we proposed a recombinant peptide-based vaccine originating from different parts of the HTLV-1 genome to induce a high immune response in mice [ 28 , 33 ]. Moreover, several subunit vaccines failed to provide preventive and consistent immune actions.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, an efficient vaccine against viral infections should generate cellular or humoral immunity. In HTLV-1 infections, various authors have recommended that both cellular and humoral immunity are needed to develop a reliable protective immune reaction [ 33 ]. A particular antibody can prevent the virus from entering target cells [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, previous reports on mice showed that more Th1/Th2 negatively correlated with the proviral load of HTLV-1 in animal models. Thus, a weak to modest Th2 immune reaction is needed to generate a suitable immune action against HTLV-1 infection and stop Th1 hypersensitivity [ 33 ]. In addition, our previous investigation and other reports showed that a high IFN-γ response is essential to protect the body from viral infection.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, previous reports and our investigation showed that high antibody responses could induce a high protective effect against HTLV-1 infection. For instance, a recent study by Shafifar et al (2022) showed that high antibody production can negatively correlate with the proviral load of HTLV-1 [ 33 ]. Additionally, a study by Kabiri et al (2018) showed that high IgG2a and IgG1 antibodies can induce TH1 and TH2 activation and offer strong protective effects against HTLV-1 infection [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…Accordingly, anti-HIV protease as a therapeutic agent invalidates further research [31]. Hence, the present study intended to introduce the Fc tag of the IgG1 antibody as a cell-mediated inducer by selective targeting of the APCs [21,25,[32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel HTLV-1 Protease: Human Fcγ1 Recombinant Fusion Molecule in the CHO Eukaryotic Expression System

Ghezeldasht

Heravi

Valizadeh

et al. 2022

Appl Biochem Biotechnol

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Human T-cell leukaemia virus type 1 (HTLV-1) is the causative agent of two life-threatening diseases, adult T cell leukaemia/lymphoma (ATLL), and HTLV-1-associated myelopathy/tropical spastic (HAM/TSP). HTLV-1 protease (HTLV-1-PR) is an aspartic protease that represents a promising target for therapeutic purposes like human immunodeficiency virus-PR inhibitors (HIV-PR). Therefore, in this study, the human Fc fusion recombinant-PR (HTLV-1-PR:hFcγ1) was designed and expressed for two applications, finding a blocking substrate as a potential therapeutic or a potential subunit peptide vaccine. The PCR amplified DNA sequences encoding the HTLV-1-PR from the MT2-cell line using specific primers with restriction enzyme sites of Not1 and Xba1. The construct was then cloned to pTZ57R/T TA plasmid and, after confirming the PR sequence, subcloned into the pDR2ΔEF1α Fc-expression vector to create pDR2ΔEF1α.HTLV-1-PR:hFcγ1. The integrity of recombinant DNA was confirmed by sequencing to ensure that the engineered construct was in the frame. The recombinant fusion protein was then produced in the Chinese hamster ovary cell (CHO) system and was purified from its supernatant using HiTrap-rPA column affinity chromatography. Then, the immunofluorescence assay (IFA) co-localisation method showed that HTLV-1-PR:hFc recombinant fusion protein has appropriate folding as it binds to the anti-Fcγ antibody; the Fcγ1 tag participates to have HTLV-1-PR:hFcγ1 as a dimeric secretory protein. The development and production of HTLV-1-PR can be used to find a blocking substrate as a potential therapeutic molecule and apply it in an animal model to assess its immunogenicity and potential protection against HTLV-1 infection. KeywordsAdult T cell leukaemia/lymphoma (ATLL) • Chinese hamster ovary cell (CHO) expression system • HTLV-1 protease • Human T-cell leukaemia virus type 1 (HTLV-1) • Recombinant Fc-fusion protein * Arman Mosavat

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Novel insights into human T‐lymphotropic virus type‐1 (HTLV‐1) pathogenesis‐host interactions in the manifestation of HTLV‐1‐associated myelopathy/tropical spastic paraparesis

Ahmadi Ghezeldasht,

Mosavat,

Rezaee

2024

Reviews in Medical Virology

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Human T‐lymphotropic virus type‐1 (HTLV‐1) was the first discovered human oncogenic retrovirus, the etiological agent of two serious diseases have been identified as adult T‐cell leukaemia/lymphoma malignancy and HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating chronic neuro‐myelopathy. Despite more than 40 years of molecular, histopathological and immunological studies on HTLV‐1‐associated diseases, the virulence and pathogenicity of this virus are yet to be clarified. The reason why the majority of HTLV‐1‐infected individuals (∼95%) remain asymptomatic carriers is still unclear. The deterioration of the immune system towards oncogenicity and autoimmunity makes HTLV‐1 a natural probe for the study of malignancy and neuro‐inflammatory diseases. Additionally, its slow worldwide spreading has prompted public health authorities and researchers, as urged by the WHO, to focus on eradicating HTLV‐1. In contrast, neither an effective therapy nor a protective vaccine has been introduced. This comprehensive review focused on the most relevant studies of the neuro‐inflammatory propensity of HTLV‐1‐induced HAM/TSP. Such an emphasis on the virus‐host interactions in the HAM/TSP pathogenesis will be critically discussed epigenetically. The findings may shed light on future research venues in designing and developing proper HTLV‐1 therapeutics.

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

Cited by 10 publications

References 53 publications

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

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

Development of a Novel HTLV-1 Protease: Human Fcγ1 Recombinant Fusion Molecule in the CHO Eukaryotic Expression System

Novel insights into human T‐lymphotropic virus type‐1 (HTLV‐1) pathogenesis‐host interactions in the manifestation of HTLV‐1‐associated myelopathy/tropical spastic paraparesis

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