“Fight flavi with flavi,” suggest the wags at Science Translational Medicine, a journal that has just published an article about the discovery of an insect-specific flavivirus, Binjari virus. This flavivirus, it turns out, is remarkably tolerant for exchange of its structural protein genes with those of pathogenic vertebrate-infecting flaviviruses. The upshot is that Binjari virus looks as though it could serve as a safe platform to generate hybrid flaviviruses. That is, such a platform that could facilitate vaccine development while avoiding the risk that humans could be infected.

The article (“A recombinant platform for flavivirus vaccines and diagnostics using chimeras of a new insect-specific virus”), which appeared December 11, was contributed by scientists based at the University of Queensland and the QIMR Berghofer Medical Research Institute.

“We were originally hoping to gain insights into how mosquito-borne viral diseases evolve—viruses like Zika, yellow fever, and dengue,” said Jody Hobson-Peters, PhD, a researcher at the University of Queensland and one of the article’s lead authors. “We were also hoping to discover new viruses that might be useful for biotechnology or as biological control agents.

“The Binjari virus stood out. While it grows to very high levels in mosquito cells in the lab, it’s completely harmless and cannot infect humans or other vertebrate species.”

Encouragingly, the newly discovered flavivirus can be engineered to house genes from related flaviviruses that cause diseases such as Zika, West Nile, dengue, and yellow fever. By serving as a platform for recombinant approaches, the new flavivirus represents a flexible and noninfectious research tool for testing diagnostics and vaccines for various infectious diseases.

“It is incredibly tolerant for genetic manipulation, allowing us to swap important genes from pathogenic viruses into the Binjari genome,” Hobson-Peters noted. “This produces hybrid, or chimeric, viruses that physically appeared identical to the disease-causing viruses under the electron microscope, but were still unable to grow in human or animal cells.”

In the current study, the scientists engineered chimeric BinJ/VIF-prME viruses that contained genes from Zika or West Nile virus, and they observed that the particles rapidly reproduced in mosquito cells but could not infect vertebrate cells.

“Cryo-electron microscopy and monoclonal antibody binding studies illustrated that the chimeric BinJ/VIF-prME virus particles were structurally and immunologically similar to their parental vertebrate-infecting flaviviruses,” the article’s authors detailed. “Pilot manufacturing in C6/36 cells suggests that high yields can be reached up to 109.5 cell culture infectious dose/mL or ≈7 mg/L. BinJ/VIF-prME viruses showed utility in diagnostic (microsphere immunoassays and ELISAs using panels of human and equine sera) and vaccine applications (illustrating protection against Zika virus challenge in murine IFNAR−/− mouse models).”

A micrograph of the Binjaru and Zika virus chimera particles. [J. Hobson-Peters et al., Science Translational Medicine (2019)]

The Binjari chimeras could be used for various applications: a vaccine based on Binjari-Zika particles protected mice from Zika virus infection, and other chimeras could replace infectious flaviviruses in several assays that test for dengue or West Nile virus. The high replication rate and noninfectious nature of Binjari virus indicates it could be easily manufactured and modified for various medical applications without posing a risk to human health.

“The main advantage of this system is that it is safe,” said one of the article’s senior authors, Andreas Suhrbier, PhD, a professor at the QIMR Berghofer Medical Research Institute. He added that he hopes that the technology can advance down the development pathway toward human applications.

“These hybrids cannot infect humans, meaning that manufacture of vaccines and diagnostic reagents don’t require the strict and expensive biosecurity infrastructure ordinarily needed to grow these pathogenic viruses,” he said. “It’s a technology that will truly revolutionize the manufacture of vaccines—supercharging high-volume vaccine development.”

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