Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments.

Summary

# Editorial Summary: Horsepox Virus as a Potential Vaccine Alternative Concerns about adverse reactions to conventional vaccinia virus (VACV)-based smallpox vaccines have prompted investigation into horsepox virus (HPXV) as a safer alternative, particularly given evidence that Jenner's original vaccine likely originated from equine sources. Researchers synthesised the entire 212 kilobase horsepox genome from chemically constructed DNA fragments, assembling ten large segments (10–30 kb each) and recombining them within cells co-infected with Shope fibroma virus to generate a fully synthetic chimeric HPXV. The resulting virus demonstrated notably reduced virulence compared to VACV—producing smaller plaques, lower titres of extracellular virus, and diminished pathogenicity in murine models—whilst retaining sufficient immunogenicity to protect against lethal VACV challenge. For equine professionals, these findings carry implications for future vaccine development, particularly if horsepox-based formulations prove safer than current preparations, though clinical translation to equine vaccination programmes remains distant. This represents a landmark application of synthetic biology to poxvirus construction and opens the possibility of rationally attenuating viral vaccines by design rather than empirical selection.

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Key Findings

• •Synthetic horsepox virus (scHPXV) was successfully constructed from chemically synthesized DNA fragments totaling 212 kbp
• •scHPXV produced smaller plaques, less extracellular virus, and exhibited lower virulence in mice compared to vaccinia virus (VACV)
• •scHPXV provided effective vaccine protection against lethal VACV challenge despite reduced virulence profile

Conditions Studied