The Eastern Province of Sierra Leone has the world?s highest incidence of Lassa fever. Members of this researchteamhavebeenworkingonLassafeverattheKenemaGovernmentHospital(KGH)forovertwelve years. The 2013-16 West African Ebola epidemic began less than a four-hourdrivefromKGHandwasthe ?rst Ebola outbreak to occur in an area close to an existing facility for viral hemorrhagic fever basic and clinical research. KGH manages up to 600 suspected Lassa fever patients per year, and Kenema and surroundingdistrictsexperiencedalargenumberofEbolacase.Wewillleverageexistingsamplesfromthese established cohorts of humans infected with Lassa fever or Ebola. While it is well established that asymptomaticormildlysymptomaticinfectionsoccurinbothLassafeverandEbola,itisunknownwhichhost factors determine the progression to fulminant hemorrhagic fever. Likewise, a substantial portion of Lassa fever and Ebola survivors develop a plethora of serious sequelae, but factors that predicate these complications remain elusive. Our research program supports both Lassa fever and Ebolasurvivorgroups. We propose to integrate experimental approaches and computational modeling to test and validate hypothesesofsigni?cancetoLassafeverandEbola.Ourassembledteamhasatrackrecordofcollaboration, uniqueexpertisewithbothLassavirusandEbolavirusandtheappropriatemultidisciplinaryrepresentationin systems and computational biology, virology, immunology, genomics, proteomics, machine learning, statisticalmethodsandmodelingrequiredtoexecutetheproposedprogram.OuroverallgoalinProject1isto generateanintegrateddatasetthatcanbeusedtobuildpredictivemodelsofpatientoutcomesinLassafever and Ebola. Studies proposed underSpeci?cAim1willde?nephysiologicalattributesthatdistinguishLassa fever and Ebola survivors and non-survivors, and individuals that develop serioussequelae.Speci?cAim2 willelucidatetheevolutionandfunctionofsuccessfulantibodynetworksinEbolaandLassafeversurvivors.T cell dynamics and the role human leukocyte antigens leading to successful clearance of Ebola virus and Lassaviruswillbede?nedinstudiesdescribedinSpeci?cAim3.InSpeci?cAim4wewilldevelopandtest predictive models for the role of host factors in Lassa fever and Ebola outcome. Project 1 on hostfactors complements the studies described in Project 2onviralfactorsandintegrateswithandutilizeseachofthe Cores.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Scripps Research Institute
La Jolla
United States
Zip Code
Suchard, Marc A; Lemey, Philippe; Baele, Guy et al. (2018) Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evol 4:vey016
Gunn, Bronwyn M; Yu, Wen-Han; Karim, Marcus M et al. (2018) A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus. Cell Host Microbe 24:221-233.e5
Saphire, Erica Ollmann; Schendel, Sharon L; Gunn, Bronwyn M et al. (2018) Antibody-mediated protection against Ebola virus. Nat Immunol 19:1169-1178
Rambaut, Andrew; Drummond, Alexei J; Xie, Dong et al. (2018) Posterior Summarization in Bayesian Phylogenetics Using Tracer 1.7. Syst Biol 67:901-904
Siddle, Katherine J; Eromon, Philomena; Barnes, Kayla G et al. (2018) Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018. N Engl J Med 379:1745-1753
Saphire, Erica Ollmann; Schendel, Sharon L; Fusco, Marnie L et al. (2018) Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection. Cell 174:938-952.e13
Holmes, Edward C; Rambaut, Andrew; Andersen, Kristian G (2018) Pandemics: spend on surveillance, not prediction. Nature 558:180-182