Deletion of multiple genes induces virulence reduction of vaccinia virus Tiantan strain.

Virus Res

Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun 130021, PR China; Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun 130122, PR China; Jiang su Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China. Electronic address:

Published: January 2020

AI Article Synopsis

  • The study aimed to create attenuated strains of the vaccinia virus by knocking out two non-essential gene fragments related to virulence and immunomodulation.
  • The researchers successfully constructed shuttle plasmids that incorporated a promoter and a screening marker, allowing for the easy identification of gene deletions.
  • The modified virus, rVTT-TC-TJ, showed reduced virulence while maintaining strong immunogenicity, indicating its potential use as a safe vaccine or viral vector.

Article Abstract

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virusres.2019.197807DOI Listing

Publication Analysis

Top Keywords

vaccinia virus
8
gene fragments
8
exogenous screening
8
screening marker
8
deletion multiple
4
multiple genes
4
genes induces
4
induces virulence
4
virulence reduction
4
reduction vaccinia
4

Similar Publications

Oncolytic vaccinia virus armed with anti-CD47 nanobody elicit potent antitumor effects on multiple tumor models via enhancing innate and adoptive immunity.

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).

View Article and Find Full Text PDF

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 PDF

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.

View Article and Find Full Text PDF

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 PDF

Multi-Component Protein Vaccine Induces a Strong and Long-Term Immune Response Against Monkeypox Virus.

Vaccines (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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!