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

Autor: Daian E Silva DSO; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil.; GIPH - Grupo Interdisciplinar de Pesquisas em HTLV, Interdisciplinary HTLV Research Group, Belo Horizonte, Brazil., Cox LJ; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil.; GIPH - Grupo Interdisciplinar de Pesquisas em HTLV, Interdisciplinary HTLV Research Group, Belo Horizonte, Brazil., Rocha AS; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil.; GIPH - Grupo Interdisciplinar de Pesquisas em HTLV, Interdisciplinary HTLV Research Group, Belo Horizonte, Brazil., Lopes-Ribeiro Á; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil., Souza JPC; Centro de Tecnologia de Vacinas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, 31270-901, Brazil., Franco GM; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil.; GIPH - Grupo Interdisciplinar de Pesquisas em HTLV, Interdisciplinary HTLV Research Group, Belo Horizonte, Brazil., Prado JLC; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil., Pereira-Santos TA; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil.; GIPH - Grupo Interdisciplinar de Pesquisas em HTLV, Interdisciplinary HTLV Research Group, Belo Horizonte, Brazil., Martins ML; GIPH - Grupo Interdisciplinar de Pesquisas em HTLV, Interdisciplinary HTLV Research Group, Belo Horizonte, Brazil.; Gerência de Desenvolvimento Técnico Científico, Fundação Centro de Hematologia e Hemoterapia do Estado de Minas Gerais - Hemominas, Belo Horizonte, Brazil., Coelho-Dos-Reis JGA; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil.; GIPH - Grupo Interdisciplinar de Pesquisas em HTLV, Interdisciplinary HTLV Research Group, Belo Horizonte, Brazil., Gomes-de-Pinho TM; Centro de Tecnologia de Vacinas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, 31270-901, Brazil., Da Fonseca FG; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil.; Centro de Tecnologia de Vacinas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, 31270-901, Brazil., Barbosa-Stancioli EF; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil. edelfb@icb.ufmg.br.; GIPH - Grupo Interdisciplinar de Pesquisas em HTLV, Interdisciplinary HTLV Research Group, Belo Horizonte, Brazil. edelfb@icb.ufmg.br.
Jazyk: angličtina
Zdroj: Virology journal [Virol J] 2023 Dec 19; Vol. 20 (1), pp. 304. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1186/s12985-023-02264-z
Abstrakt: Background: 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.
Methods: 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.
Results: T CD4 + and T CD8 + lymphocytes cells stimulated by HBZ-peptides (HBZ 42-50 and HBZ 157-176 ) 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 +High /CD62L -Low ), 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.
Conclusions: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.
(© 2023. The Author(s).)
Databáze: MEDLINE
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