August 30, 2016 SPADA Meeting Book

Virus Eradication – Considerations to 1999

 Additional Global Commission sanctioned research – reflect (new) technologies of the time  Cloning of Variola virus genomes in representative segments –  Hybrid viruses* (1981): proof of recombination/“transfection” • Scientific Advisory Group of Experts (1984) o Vaccine research using Vaccinia virus vector  Sequencing of virus genomes – • 1993 - Two complete Variola virus “major” genomes available  Bioterrorism threat once vaccination program ceases  Decision to prohibit genetic manipulation of Variola virus , restrict access to genomic elements and genome  Reports that Russia had attempted to “weaponize” Variola virus *Sam andDumbell Expression ofpoxvirus DNA in coinfected cells and marker rescue of thermosensitive mutants by subgenomic fragments ofDNA  Annales de virologie, 1981 Smallpox Research Agenda: Focused on Preparedness Needs • Institute of Medicine (IOM) Report recommendations for “Assessment of Future Scientific Needs for Live Variola Virus ” (1999) have helped to frame the research agenda. • Protocols approved by WHO technical subcommittee • Research updates provided annually to the WHO Advisory Committee for Variola Virus Research • Collaborative HHS (largely CDC) and DoD (largely USAMRIID) • All U.S. work with live Variola virus occurs within the BSL-4 containment laboratory at the CDC • Inspected regularly by U.S. security and biosafety authorities and WHO biosafety teams

• Genetic manipulation of Variola virus not authorized by WHO – 1994 Ad hoc Orthopoxvirus Advisory Committee recommendation

• Full genomes of Variola virus can only be maintained at the 2 WHO CCs • No lab can have more than 20% of the Variola virus genome, except a WHO Collaborating Center

• All research findings to be made available to the international scientific community