The purpose of this study was to knock out two non-essential gene fragments (TC7L-TK2L and TJ2R) related to virulence, immunomodulation, and host range in the vaccinia virus Tian Tan strain (VTT), and combining with double-label screening and exogenous screening marker knockout techniques to construct attenuated strains with multiple gene deletions(rVTT-TC-TJ). The shuttle plasmids pSK-TC and pSK-TJ were constructed by designing 2 pairs of recombinant arms, combined with poxvirus early and late complex strong promoter pE/L and exogenous screening marker enhanced green fluorescent protein(EGFP). The results showed that knocking out the two gene fragments does not affect the replication ability of the virus and displays a good genetic stability. Furthermore, a series of in vivo and in vitro experiments demonstrate that although virulence of rVTT-TC-TJ is attenuated significantly, high immunogenicity was maintained. These results support the potential development of rVTT-TC-TJ as a safe viral vector or vaccine.
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http://dx.doi.org/10.1016/j.virusres.2019.197807 | DOI Listing |
J Immunother Cancer
December 2024
Department of Clinical Laboratory, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China
Objective: Targeting CD47 for cancer immunotherapy has been studied in many clinical trials for the treatment of patients with advanced tumors. However, this therapeutic approach is often hampered by on-target side effects, physical barriers, and immunosuppressive tumor microenvironment (TME).
Methods: To improve therapeutic efficacy while minimizing toxicities, we engineered an oncolytic vaccinia virus (OVV) encoding an anti-CD47 nanobody (OVV-αCD47nb).
JYNNEOS, a third-generation smallpox vaccine, is integral to monkeypox virus (MPXV) control efforts, but the durability of this modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine's effectiveness is undefined. We optimized and used a plaque reduction neutralization test (PRNT) with authentic clade IIa MPXV and vaccinia virus to assess antibody responses over 12 months in 8 donors vaccinated with 2 doses of JYNNEOS. One donor previously received the ACAM2000 vaccine; 7 donors were smallpox vaccine-naive.
View Article and Find Full Text PDFClin Cancer Res
January 2025
University of Leeds, Leeds, United Kingdom.
Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous or intratumoural administration routes.
Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine to fifteen mCRC patients.
CPT Pharmacometrics Syst Pharmacol
January 2025
Astellas Pharma Inc., Northbrook, Illinois, USA.
The antitumor efficacy of an intratumoral injection of a genetically engineered oncolytic vaccinia virus carrying human IL-7 and murine IL-12 genes (hIL-7/mIL-12-VV) was demonstrated in CT26.WT-bearing mice. In the CT26.
View Article and Find Full Text PDFVaccines (Basel)
December 2024
State Key Laboratory of Pathogens and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China.
Background/objectives: Since 2022, outbreaks of monkeypox have raised widespread concern and have been declared a public health emergency of international concern by the World Health Organization. There is an urgent need to develop a safe and effective vaccine against the monkeypox virus (MPXV). Recombinant protein vaccines play a significant role in the prevention of infectious diseases due to their high safety and efficacy.
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