The Global Virome Project The Beginning of the End of the - - PowerPoint PPT Presentation

The Global Virome Project

The Beginning of the End

• f the

Pandemic Era

We a are n not prepared f for

• r 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

• f their laboratory-enhanced variants

The risks posed by these dual threats are

• utpacing 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

50 100 150 200 250 300 1945 1955 1965 1975 1985 1995 2005 2015 2025 2035 2045 2055

Actual Projected

Decades Number of EVD Events Each year, approx. 3 new Viral Diseases emerge Driven by

• Population expansion (1.6

billion in 1900 to 11.5 billion people in 2100)

• Increased encroachment

into wildlife habitat which accelerates the “spillover” from wildlife to humans

Source: Jones et al. (2008) Nature

The “nat atural al” t threat at f from v virus uses i is incr creas asing ing

HIV Nipah Avian Influenza SARS Zika H1N1 Ebola MERS

The he thr threat fr from

• m “

“lab-enha hanced” viruse ses i is i intensi sify fying

https://www.theguardian.com/commentisfree/cifamerica/2011/sep/15/anthrax-iraq

• 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

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-

• ccurring 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

Of the total, 500,000 - 700,000 viral species have the potential to cause human infection

• For every “known” corona virus

(e.g. MERS) there are an estimated 3-5,000 distinct “unknown” viruses

• f 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: Virus Evolution, 2017, 3(1): vex012

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/ genomic sequence generation Sequence database

Viral Atlas Database A comprehensive ecologic and genetic database on all naturally-

• ccurring viruses

Metadata on “viral ecology” – host range, geographic distribution, epidemiology

Enabling An Enhanced Public Health Tool Box

Advanced development of “broad spectrum” countermeasures for natural and laboratory-enhanced “high risk” viruses

Ability to target high impact interventions to PREVENT “spillover” at high risk animal- human interface

Enhanced Public Health “Tool Box”

Naturally-Occurring Viruses Laboratory-Enhanced Viruses

Targeted surveillance enables early DETECTION and effective RESPONSE to future spillover” events Ability to rapidly recognize a lab-enhanced virus against the Viral Atlas database on viral ecology and genomic sequence

GVP: Impact

Im Impa pact 1: De : Development o

• f B

Broad Co Countermeasures

GVP

will enable the comparative analysis of thousands of members of each viral family and the advanced development of next generation countermeasures that are broadly effective – rather than against individual viruses (e.g. MERS, SARS)

MERS SARS

Converting Virology into a data-rich field

Thousands of other Corona Viruses

Universal Corona Virus Vaccine

Impac act 2 2: Pa Pandemic ic/Ep /Epid idemi mic Preven ention

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 threat and the targeting of measures to prevent spillover

Minimizing the Risk of Spillover

Drive Targeted, High-Impact Risk Mitigation

Virus surveillance and collection Virus isolation/ genomic sequence generation Sequence database Bioinformatics Comprehensive database of all naturally-occurring viruses

GVP Molecular-based Surveillance

Impact ct 3: 3: Ra Rapid id I Identifica cation of

• f lab-enhance

ced vi viru ruses

Enables Rapid Confirmation of lab- enhanced/unnatural phenotype

Im Impa pact 4 4: : The he “Halo E

• 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)

• 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

Stages of “Emergence”

• 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

Paral arallels t to the the Hum Human Ge Genome Project

GVP: Feasibility

Feasibi bili lity: : Larg rge sca cale “ “Pr Proof o

• f Co

Concept”

• Spanning >35 countries
• Over $170 million invested between 2009-present

The feasibility of GVP was validated through USAID’s PREDICT Project

Zoonotic disease surveillance - from how to safely collect and handle samples, laboratory diagnostics, and data management and interpretation.

Trained field & lab staff Optimized Sampled labs wild animals

Viruses detected Systems and Capacities Built

Feasibi bili lity: : Extra rapola

• lating N

Number o r of Sample les

Discovery Curves Show the Number of Samples Requiredmber 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

With the collaboration of Prof. Ralph Baric in North Carolina University - Menachery et al., Nat Med, 2015; PNAS, 2016

SARS-CoV and SHC014 SARS-CoV and WIV1

Serological evidence of SL-CoV infection in human

Severe acute diarrhea syndrome (SADS)

• From 28 October 2016, fatal

swine disease outbreaks were

• bserved 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

• the

he Sou

• urce

Mammals and water fowl are viral reservoirs

Mammalian Habitat ranges Waterfowl breeding hotspots

• Mammalian biodiversity
• Uniqueness of diversity in field sites
• Zoonotic viral yield
• Access costs of field work
• Overlap between sample sites

Maximize: Minimize:

Approac ach: h: Prioritiz tizin ing S Sites f for GVP S Samplin ing

• 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

Predicting Zoonotic Risk:

Ap Approa

• ach

ch: Zeroin ing I In on

• n Mammali

lian S Sampling S Sites

Sampling Sites Selected:

• 108 Sampling Sites (SS) selected
• 3 Phases proposed for sample collection

covering: 36, 43, and 29 SUs

• Total cost: $968,220,000
• A minimal number of efficient, high-

diversity sample units were selected from a global grid

• Each sample site covers 20,000 km2

Selection Process:

The he Glo Global Vi Virome me: Site S Sele lection

Phase 1: 10 countries, 1,562 mammals, $425.2 M Phase 2: 15 countries, 994 mammals, $350.9 M Phase 3 23 countries, 423 mammals, $192.1 M

Over 10 years, will target: 68.5% of global mammalian viruses, by sampling 63.5% of global mammalian diversity, to find 71% of potential zoonoses

108 Global Sampling Sites

GVP VP: Ma Making t the he Unknown Kno KnownGVP

Phase 2: 24% Phase 1: 38% Phase 3: 9%

85% of Global Virome

Water fowl: 14%

The G Global al V Virome P Proje ject ct: In P n Pract actice ice

• Optimal targeting: 10 years, 85+% of likely zoonoses, ~$1

billion – will enable the fast tracking of a high impact “tool box” for preventing, detecting, and responding to dual threats.

• The modeling strategy is not wholly prescriptive – many other

sites could potentially contribute to the GVP without significantly increasing costs.

• Using host factors, we can further optimize within chosen

sampling units to decide which species to target first.

• The models can be used as a monitoring tool to verify

predictions about:

• Saturation rate of viral curves
• Rate of sample acquisition across various sites
• Analytical approaches (modeling and lab-based) to assess zoonotic

potential of discovered viruses and whether site selection is delivering a higher rate of zoonotic discovery

Phase 1: First Wave Countries

GVP : : “Fi “First t Wave” C e” Countr try S y Sites

Costa Rica: 1 site Cameroon: 3 sites Uganda: 1 site China: 4 sites Thailand: 1 site

• 10 sampling sites in 5 countries
• 816 unique mammal species targeted
• 22% of the global mammalian virome captured
• $217.6M

5 initial GVP launch countries: Costa Rica, Cameroon, Uganda, Thailand, China

Phase 1: Second Wave Countries

GV GVP: “Seco cond nd Wave” C e” Countr try S y Sites

Brazil: 7 sites DR Congo: 2 sites Indonesia: 7 sites

• 27 sampling sites in 5 countries
• 746 mammal species targeted
• 19% of the global mammalian virome captured
• $207.6M

5 GVP launch countries: Colombia, Brazil, DR Congo, Vietnam, Indonesia

Colombia: 8 sites Vietnam: 3 sites

GVP: : Core re P Principle les

The GVP is committed to achieving its goals through core principles that:

• Embrace an international scope, while fostering

local ownership

• Promote equitable access to data and benefits
• Foster transparency
• Build national capabilities for “prevention,

detection and response” for emerging viral threats

• Foster global ownership through an international

alliance

GVP O Organiz anizatio iona nal Par Partne ners i incl clude de:

The END

• f the

Pandemic Era