MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA. (November 2021)

• Record Type: Journal Article
• Authors: Del Médico Zajac, María Paula; Molinari, Paula; Gravisaco, María José; Maizon, Daniel Omar; Morón, Gabriel; Gherardi, María Magdalena; Calamante, Gabriela
• Is Part Of: Molecular immunology. Volume 139(2021)
• Page Start: 115
• Page End: 122
• Publication Date: 2021-11
• Subjects: MVA Modified vaccinia Ankara virus -- OVA ovalbumin -- VACV vaccinia virus -- IL-18 bp interleukin-18 binding protein -- CEFs chicken embryo fibroblasts -- MO5 B16F10-OVA melanoma-derived cells -- TV transfer vector -- pE/L poxviral synthetic early-late promoter -- GUS β-glucuronidase enzyme -- pH6 promoter of vaccinia virus H6 gene -- TK thymidine kinase -- dpv days post vaccination -- Con A Concavalin A -- IFN-γ Interferon gamma -- ICS intracellular cytokine staining -- CTLs cytotoxic T lymphocytes -- MFI media fluorescence intensity -- i.p. intraperitoneal -- i.v. intravenous -- s.c. subcutaneous -- i.n. intranasal; MVA -- Optimized vectors -- IL-18 bp -- OVA protein -- Immune response -- Vector efficacy; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.08.004
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: MVAΔ008-OVA induces ex vivo IFN-γ secretion and in vivo cytotoxicity response against OVA. This response has higher magnitude than the elicited by the conventional MVA vector. Recombinant MVAs induce full protection against MO5 challenge (prophylactic scheme). In a therapeutic scheme, both MVAs delay tumor growth and prolong mice survival. Abstract: Modified vaccinia Ankara virus (MVA) is extensively used as a vaccine vector. We have previously observed that MVAΔ008, an MVA lacking the gene that codes for interleukin-18 binding protein, significantly increases CD8+ and CD4+ T-cell responses to vaccinia virus (VACV) epitopes and recombinant HIV antigens. However, the efficacy of this vector against pathogens or tumor cells remains unclear. Thus, the aim of this study was to evaluate the cellular immune response and the protection induced by recombinant MVAs encoding the model antigen ovalbumin (OVA). We used the MO5 melanoma tumor model (OVA-expressing tumor) as an approach for evaluating the vector-induced efficacy. Our results show that MVAΔ008-OVA (optimized vector) induced higher in vivo specific cytotoxicity and ex vivo T-cell IFN-γ responses against OVA than the conventional MVA vector. Importantly, the recombinant vectors were capable of controlling MO5 tumor growth. Indeed, the administration of MVAΔ008-OVA or MVA-OVA in prophylactic and therapeutic schemes provided total protection and longer survival of mice, respectively. Overall, our results demonstrate the improved immunogenicity and the protective capacity of MVAΔ008 against a heterologous model antigen. These findings suggest that MVAΔ008 constitutes an excellent candidate for vaccine development against pathogens or cancer therapy.