Public Release: 

Mice immunized with synthetic horsepox protected against vaccinia virus

Horsepox virus synthesized from DNA fragments may offer alternative to the current smallpox vaccine

PLOS

Immunization with a synthetic horsepox virus offers mice similar protection to immunization with vaccinia virus against a lethal dose of vaccinia, according to a study published January 19, 2018 in the Open Access journal PLOS ONE by Ryan Noyce from the University of Alberta, Canada, and colleagues.

The vaccinia virus (VACV) used as a live vaccine protects against smallpox, but is associated with serious side effects. As VACV shows close similarities to the horsepox virus (HPXV), Noyce and his colleagues tested whether HPXV could offer an alternative to the live VACV vaccine.

The only identified specimen of HPXV is unavailable for investigation and it is believed that the HPXV virus has been eradicated. Using similar techniques already used to generate synthetic polio and influenza viruses, the team successfully generated a chimeric HPXV virus using chemically-synthesized DNA fragments based on the previously published HPXV and VACV genomes. They then used cell culture to activate the virus.

The researchers found that the chimeric HPXV produced fewer extracellular virus particles and was less virulent than VACV. Mice intranasally infected with chimeric HPXV developed similar levels of protective antibodies to mice inoculated with VACV, but had less severe reactions. When challenged with lethal dosages of VACV, mice previously immunized with chimeric HPXV were protected against severe illness.

The virus synthesized in the present study is less virulent than the modern strain of vaccinia virus, and therefore does not cause an immediate biosafety or biosecurity risk. However, the authors acknowledge that the generation of the first synthetic poxvirus presents risks of future misuse. The study demonstrates that the technological capacity exists. However, the work also highlights how synthetically engineered viruses might have potential in improving vaccines.

This work was conducted with the knowledge and support of the University of Alberta's biosafety program. Research facilities involved in the project are compliant with the Canadian Biosafety Standard and are properly registered with the Public Health Agency of Canada under the Human Pathogens and Toxins Act. In recognition of the biosecurity risks, the authors also reported their findings to the World Health Organization (WHO) Advisory Committee of Variola Virus Research.

PLOS is committed to the widespread dissemination of research and to responsible publication standards. To this end, PLOS maintains a Dual Use Research of Concern Committee consisting of in-house and external experts. The committee assessed the risks and benefits of publication of the present study and supported publication on the basis that it does not provide new information specifically enabling the creation of a smallpox virus, but uses known methods, reagents and knowledge that have previously been documented and used in the synthesis of other viruses. That the DNA synthesis in this study was performed by a commercial third-party service is not only a testament to the present state of technology, but also underlines the safeguards and risk assessments that need to be considered for studies of this type. PLOS supports an open debate about the associated biosafety and biosecurity concerns.

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In your coverage please use this URL to provide access to the freely available article in PLOS ONE: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188453

Citation: Noyce RS, Lederman S, Evans DH (2018) Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments. PLoS ONE 13(1): e0188453. https://doi.org/10.1371/journal.pone.0188453

Funding: This work was performed under a research agreement with Tonix Pharmaceuticals. The funder played a role in the formulation of the project, the decision to publish, and preparation of the manuscript.

Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: DHE and RDN provide consultation services to Tonix Pharmaceuticals Ltd. SL is the co-founder, CEO and chairman of Tonix Pharmaceuticals Ltd. A US patent application (Synthetic chimeric poxviruses; Application No.: 62/434,794; first provisional filed November 2, 2016) has been filed on behalf of the Governors of the University of Alberta and Tonix Pharmaceuticals claiming the three authors as co-inventors. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The DNAs and reconstructed HPXV strains can be provided upon request. Please direct all such enquiries to Dr. S. Lederman, c/o Tonix Pharmaceuticals.

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