Non-replicating Newcastle Disease Virus as an adjuvant for DNA vaccine enhances antitumor efficacy through the induction of TRAIL and granzyme B expression

Mohebbi, A and Ebrahimzadeh, M and Baghban Rahimi, S and Saeidi, M and Tabarraei, A and Mohebbi, S and Shirian, S and Gorji, A and Ghaemi, A (2019) Non-replicating Newcastle Disease Virus as an adjuvant for DNA vaccine enhances antitumor efficacy through the induction of TRAIL and granzyme B expression. Virus Research, 261.

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Abstract

The potential of non-replicating Newcastle Disease Virus (NDV) as an adjuvant for DNA vaccination remains to be elucidated. To assess the therapeutic effects of DNA vaccine (HPV-16 E7 gene) adjuvanted with NDV, female C57/BL6 mice were inoculated with murine TC-1 cells of human papillomavirus (HPV)-related carcinoma, expressing human papillomavirus 16 (HPV-16) E6/E7 antigens, and immunized with DNA vaccine alone or pretreated with NDV. One week after third immunization, Cytotoxic T lymphocytes (CTLs), splenocyte proliferation, cytokine balance (IFN-γ IL-4 and IL-12 secretions) and intratumoral expression of cytotoxicity related proteins in tumor lysates were investigated. The results showed that treatment with non-replicating NDV prior to DNA vaccine induced tumor-specific cytolytic and splenocyte proliferation responses. The levels of cytokines IL-12, IL-4 and IFN–γ after treating with combined E7-DNA -non-replicating NDV (NDV-DNA Vaccine) were significantly higher than those of control groups. The intratumoral granzyme B and Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL)-mediated apoptosis was also significantly increased. Tumor therapeutic experiments showed that the NDV pretreatment could reduce the tumor progression of established E7-expressing TC-tumors. Taken together these data suggest that the significant antitumor responses evidenced during treatment with non-replicating NDV prior to DNA vaccine are due, in part, to strong E7-induced cellular immunity and enhanced expression of cytotoxicity related proteins in the tumor microenvironment. These observations indicated the potential of non-replicating NDV as an adjuvant for enhancing therapeutic DNA vaccines -induced immunity and antitumor responses.

Item Type: Article
Uncontrolled Keywords: Cervical cancer, DNA vaccine, Granzyme B, HPV-16 E7, Newcastle Disease Virus, TRAIL
Subjects: W General medicine- Health professions
WC Communicable Diseases
WD Nutrition Disease and metabolic diseases
WK Endocrine System
QU Biochemistry
QW Microbiology and Immunology
Divisions: Faculty of Medicine > Basic Sciences Academic Groups > Department of Microbiology
Depositing User: Unnamed user with email nazari@skums.ac.ir
Date Deposited: 06 Apr 2019 10:11
Last Modified: 17 Apr 2019 04:02
URI: http://eprints.skums.ac.ir/id/eprint/7594

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