Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein

Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV...

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Bibliographic Details
Published in:Virology journal 2023-12, Vol.20 (1), p.304-304, Article 304
Main Authors: Daian E Silva, D S O, Cox, L J, Rocha, A S, Lopes-Ribeiro, Á, Souza, J P C, Franco, G M, Prado, J L C, Pereira-Santos, T A, Martins, M L, Coelho-Dos-Reis, J G A, Gomes-de-Pinho, T M, Da Fonseca, F G, Barbosa-Stancioli, E F
Format: Article
Language:English
Subjects:
Analysis
Animals
Antigens
Basic-Leucine Zipper Transcription Factors
CD4 antigen
CD44 antigen
CD8 antigen
CD8-Positive T-Lymphocytes
Cell activation
Cell proliferation
Chronic infection
Cloning
Cytotoxicity
DNA
DNA binding proteins
DNA vaccines
Dosage and administration
E coli
Effector cells
Enzyme-linked immunosorbent assay
Ethylenediaminetetraacetic acid
Flow cytometry
Granzyme B
Granzymes - genetics
HBZ
Health aspects
Human T-lymphotropic virus 1
Humans
Immune response
Immune response (humoral)
Immunogenicity
Immunoglobulin G
Immunological memory
Immunosurveillance
Immunotherapy
Infection
Infections
L-selectin
Leucine zipper proteins
Lymphocytes T
Memory (Computers)
Memory cells
Mice
Patient outcomes
Peptides
Plasmid DNA vaccine (pcDNA3.1(+)-HBZ)
Proteins
Recombinant Modified Vaccinia virus Ankara (MVA-HBZ)
Retroviridae Proteins - genetics
Splenocytes
T cells
Testing
Tumor Necrosis Factor-alpha
Tumor necrosis factor-α
Vaccine
Vaccines
Vaccines, DNA - genetics
Vaccinia virus - genetics
Viral Proteins - metabolism
γ-Interferon
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Summary:Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4 and T CD8 ) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. T CD4 and T CD8 lymphocytes cells stimulated by HBZ-peptides (HBZ and HBZ ) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8 cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44 /CD62L ), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8 T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.
ISSN:1743-422X
1743-422X
DOI:10.1186/s12985-023-02264-z