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Development of a gene-deleted live attenuated candidate vaccine against fish virus (ISKNV) with low pathogenicity and high protection.

ABSTRACT: Aquaculture provides important food, nutrition, and income sources for humans. However, aquaculture industry is seriously threatened by viral diseases. Infectious spleen and kidney necrosis virus (ISKNV) disease causes high mortality and economic losses to the fish culture industry in Asia and has been listed as a certifiable disease by the International Epizootic Office. Vaccine development is urgent to control this disease. Here, a gene-deleted live attenuated candidate vaccine (ΔORF022L) against ISKNV with low pathogenicity and high protection was developed. ΔORF022L replicated well in mandarin fish fry-1 cells and showed similar structure with wild-type ISKNV. However, the pathogenicity was significantly lower as 98% of the mandarin fish infected with ΔORF022L survived, whereas all those infected with wild-type ISKNV died. Of importance, 100% of the ΔORF022L-infected fish survived the ISKNV challenge. ΔORF022L induced anti-ISKNV specific antibody response and upregulation of immune-related genes. This work could be beneficial to the control of fish diseases.

SUBMITTER: Zeng R

PROVIDER: S-EPMC8261673 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Glioblastoma (GBM) is the deadliest type of brain tumor, and glioma stem cells (GSCs) contribute to tumor recurrence and therapeutic resistance. Thus, an oncolytic virus targeting GSCs may be useful for improving GBM treatment. Because Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we investigated the safety and efficacy of a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the treatment of human GBM in a GSC-derived orthotopic model. Intracerebral injection of ZIKV-LAV into mice caused no neurological symptoms or behavioral abnormalities. The neurovirulence of ZIKV-LAV was more attenuated than that of the licensed Japanese encephalitis virus LAV 14-14-2, underlining the superior safety of ZIKV-LAV for potential GBM treatment. Importantly, ZIKV-LAV significantly reduced intracerebral tumor growth and prolonged animal survival by selectively killing GSCs within the tumor. Mechanistically, ZIKV infection elicited antiviral immunity, inflammation, and GSC apoptosis. Together, these results further support the clinical development of ZIKV-LAV for GBM therapy.IMPORTANCE Glioblastoma (GBM), the deadliest type of brain tumor, is currently incurable because of its high recurrence rate after traditional treatments, including surgery to remove the main part of the tumor and radiation and chemotherapy to target residual tumor cells. These treatments fail mainly due to the presence of a cell subpopulation called glioma stem cells (GSCs), which are resistant to radiation and chemotherapy and capable of self-renewal and tumorigenicity. Because Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we tested a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the treatment of human GBM in a human GSC-derived orthotopic model. Our results showed that ZIKV-LAV retained good efficacy against glioblastoma by selectively killing GSCs within the tumor. In addition, ZIKV-LAV exhibited an excellent safety profile upon intracerebral injection into the treated animals. The good balance between the safety of ZIKV-LAV and its efficacy against human GSCs suggests that it is a potential candidate for combination with the current treatment regimen for GBM therapy.

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Development of a gene-deleted live attenuated candidate vaccine against fish virus (ISKNV) with low pathogenicity and high protection.

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