The Global Virome Project The Beginning of the End of the Pandemic Era
We a are n not prepared f for or t the Dual T Threa reats s Posed by Em Emer ergi ging I Infecti tious D Dis iseas ases The world is facing an increasing dual threat from I. the natural emergence of deadly infectious pathogens, and II. the accidental &/or intentional release of their laboratory-enhanced variants The risks posed by these dual threats are outpacing our ability to develop effective and timely countermeasures There is an urgent need to be able to prepare our responses in ADVANCE of any future threats – natural and lab-enhanced
The “nat atural al” t threat at f from v virus uses i is incr creas asing ing Each year, approx. 3 new Viral Diseases emerge 300 Number of EVD Events Actual 250 Ebola Projected Driven by MERS 200 Avian Influenza • Population expansion (1.6 Zika SARS H1N1 Nipah billion in 1900 to 11.5 150 HIV billion people in 2100) 100 • Increased encroachment 50 into wildlife habitat which 0 1945 1955 1965 1975 1985 1995 2005 2015 2025 2035 2045 2055 accelerates the “spillover” from wildlife to humans Decades Source: Jones et al . (2008) Nature
The he thr threat fr from om “ “lab-enha hanced” viruse ses i is i intensi sify fying • Gain of function and “DIY” research is elevating the risk of the accidental and/or deliberate release of deadly novel biological agents • Historical examples demonstrate both indirect and direct impacts of this threat • Illnesses and deaths • Mass hysteria and panic https://www.theguardian.com/commentisfree/cifamerica/2011/sep/15/anthrax-iraq
The Global al V Virome P Proje ject ct The Global Virome Project (GVP) is a ten year global partnership to better prepare the world for these dual threats, by: • Developing a global database of virtually all of the planet’s naturally- occurring viral threats • Transforming the world of emerging diseases into a data-rich field – driving the advanced development of countermeasures, against all future threats, and • Enabling rapid detection of natural and laboratory-enhanced threats
GVP: Making the Unknown Known
GVP VP: Ma Making futu ture t threa eats s known ~1.6 million natural viral species spanning 23 “high consequence” viral families are estimated to be circulating in mammals and water fowl
GV GVP: Making ng futu ture threats known • For every “known” corona virus (e.g. MERS) there are an estimated 3-5,000 distinct “unknown” viruses of the same corona virus family circulating among wild animals* • It is likely the same holds for HIV and retroviruses, Ebola and filoviruses, Zika and flaviviruses, etc. – there are thousands of “unknown” viruses for each viral family. *Anthony et al: Global patterns in coronavirus diversity: Of the total, 500,000 - 700,000 Virus Evolution, 2017, 3(1): vex012 viral species have the potential to cause human infection
GV GVP: M Making ng futu ture t threa eats s known The Global Virome Project presents a path to identifying and characterizing those viruses that have the greatest potential to infect humans, and their laboratory enhanced variants - so we can prepare for them before they jump to us
GVP B Build lds a a Compre rehe hensive V Viral D Databa base GVP viral surveillance and collection Virus isolation/ Metadata on “viral genomic sequence ecology” – host generation range, geographic distribution, epidemiology Sequence database Viral Atlas Database A comprehensive ecologic and genetic database on all naturally- occurring viruses Enabling An Enhanced Public Health Tool Box
Enhanced Public Health “Tool Box” Naturally-Occurring Viruses Laboratory-Enhanced Viruses Ability to target high impact interventions to PREVENT “spillover” at high risk animal- Ability to rapidly recognize a human interface lab-enhanced virus against the Targeted surveillance enables Viral Atlas database on viral early DETECTION and effective ecology and genomic sequence RESPONSE to future spillover” events Advanced development of “broad spectrum” countermeasures for natural and laboratory-enhanced “high risk” viruses
GVP: Impact
Im Impa pact 1: De : Development o of B Broad Co Countermeasures Converting Virology into a data-rich field GVP Universal Corona Virus will enable the comparative analysis of thousands of Vaccine members of each viral family and the advanced development of next MERS generation countermeasures SARS that are broadly effective – rather than against individual Thousands of other Corona Viruses viruses ( e.g. MERS, SARS)
Impac act 2 2: Pa Pandemic ic/Ep /Epid idemi mic Preven ention Drive Targeted, High-Impact Risk Mitigation GVP will enable through detailed characterization of every virus's ecologic profile – spanning host range, geographic distribution, and epidemiology – the identification of viruses that pose the greatest potential Minimizing the Risk of Spillover threat and the targeting of measures to prevent spillover
Impact ct 3: 3: Ra Rapid id I Identifica cation of of lab-enhance ced vi viru ruses GVP Molecular-based Surveillance Virus surveillance Virus isolation/ and collection genomic sequence generation Sequence Bioinformatics database Comprehensive database of all naturally-occurring viruses Enables Rapid Confirmation of lab- enhanced/unnatural phenotype
Im Impa pact 4 4: : The he “Halo E o Effect” As in the Human Genome • Project, data generated by the GVP will dramatically accelerate the development of new diagnostic & analytic tools Data generated will have • unanticipated impact – for example, the identification of potential viral threats to livestock or unknown viral causes of chronic diseases like cancer
The “ e “Halo E Effec ect” ( ” (cont nt) Stages of “Emergence” Investing in a global GVP database will • serve as a critically important “snap shot in time” on viral ecology, epidemiology, and genetics • GVP’s surveillance and laboratory platforms have the potential to remain beyond the GVP as a long term system for monitoring evolving viral threats – as well as future “man made” threats, ensuring early detection and rapid deployment of biomedical and preventive countermeasures
Paral arallels t to the the Hum Human Ge Genome Project • An audacious but doable visionary project • Clear metrics and goals • Disruptive and transformative • Can be done in phases where each phase itself generates useful information • The potential to change the way we do science and engage global health
GVP: Feasibility
Feasibi bili lity: : Larg rge sca cale “ “Pr Proof o of Co Concept” The feasibility of GVP was validated through USAID’s PREDICT Project Spanning >35 countries Over $170 million invested between 2009-present Systems and Capacities Built Viruses detected Trained Optimized Sampled Zoonotic disease surveillance - from how to safely collect and handle samples, laboratory diagnostics, and data management and interpretation. labs wild animals field & lab staff
Feasibi bili lity: : Extra rapola olating N Number o r of Sample les Discovery Curves Show the Number of Samples Required mber of samples required to discover most of the unknown viruses • PREDICT research has demonstrated that far fewer samples than previously expected are required to identify all the viruses in a given species • These viral discovery curve studies provide a roadmap to sampling needs for GVP
Feasibi bili lity: : Targ rgeting “ “High R h Risk” S Species
Fea easib ibil ilit ity: Ran anking Whic Which Viru iruses Are Are Mo Most “R t “Ris isky”
Pathogenesis of SL-CoVs in transgenic mice SARS-CoV and SHC014 SARS-CoV and WIV1 With the collaboration of Prof. Ralph Baric in North Carolina University - Menachery et al., Nat Med, 2015; PNAS, 2016
Serological evidence of SL-CoV infection in human
Severe acute diarrhea syndrome (SADS) • From 28 October 2016, fatal swine disease outbreaks were observed in a pig farm in Qingyuan, Guangdong Province, China • On 2nd May 2017, the disease has resulted in the death of 24,693 piglets from four farms. In Farm A alone, 64% (4659/7268) of all piglets born in February died. • A coronavirus similar to bat CoV HKU2 was detected in diseased pigs
Diverse SADS-CoV related viruses were detected in bats Zhou et al., unpublished results
GVP: The Approach
GVP VP: Ge Get t to o the he Sou ource Mammals and water fowl are viral reservoirs Waterfowl breeding hotspots Mammalian Habitat ranges
Approac ach: h: Prioritiz tizin ing S Sites f for GVP S Samplin ing Maximize: - Mammalian biodiversity - Uniqueness of diversity in field sites - Zoonotic viral yield Minimize: - Access costs of field work - Overlap between sample sites Predicting Zoonotic Risk: - Host traits used to predict zoonotic risk: • Order and habitat range size • Human population in habitat range Urban/rural human population ratio • • Human population density • Zoogeographic region of habitat
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