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Principal Investigator: Kristian Graugaard Andersen
Organization: SCRIPPS RESEARCH INSTITUTE, THE
Fiscal Year: 2024
Award: $642,549
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary - Project 2
The objective of Project 2 is to investigate the complex interplay of virus genetics and host immunity in
determining epidemiology and outcome of infection with Lassa virus, Ebola virus, and SARS-CoV-2. Our
central hypothesis is that both host and virus factors play key roles in determining the severity of clinical
outcomes including survival, disease severity and the development of long-term sequelae. To test this
hypothesis, we will investigate viral genetics, development of host immunity, and how these processes
interact as a result of viral infection or vaccination. In focusing on the host-pathogen interface, we will
complement the host-focused studies from Project 1 to better understand the complex factors that
determine the clinical outcome and epidemiology of Lassa, Ebola, and COVID-19.
To accomplish this, we will complete the following: In Aim 1, we will refine viral sequencing techniques to
generate large catalogs of Lassa virus and SARS-CoV-2 genomic diversity. We will then integrate these
data with environmental and demographic data and apply phylodynamic models to identify virus
mutations and variants most likely to have an effect on disease severity. In Aim 2, we will perform single
cell sequencing and transcriptomics to deeply characterize the evolution of adaptive immunity in
response to acute Lassa virus infection or vaccination. We will also isolate monoclonal antibodies from
individuals previously infected with or vaccinated against Lassa virus, Ebola virus, or SARS-CoV-2 to
understand the diversity of the human humoral response. In Aim 3, we will extend the multi-omics work
proposed in Aim 2 to individuals infected with different viral variants, with the goal of developing a
predictive model of immune response and clinical outcome. This model will integrate the systems
serology data from Project 1 as part of a framework of repeated cycles of experimental data generation,
integration, application, validation, and refinement to identify predictive biological markers of human
disease and outbreak dynamics. Finally, in Aim 4, we will validate the findings from the previous aims in a
BSL-4 setting (the biosafety level required for working with live Ebola or Lassa virus) and use the results of
animal models to further refine our predictive models of clinical outcome.
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global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Seasons><Serology><Seroprevalences><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome coronavirus disease><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Sierra Leone><Single cell seq><System><Systems Biology><Techniques><Technology><Testing><Vaccinated><Vaccination><Validation><Variant><Variation><Viral><Viral Diseases><Viral Genetics><Viral Genome><Viral Hemorrhagic Fevers><Virulence><Virus><Virus Diseases><Work><Wuhan coronavirus><adaptive immunity><bio-markers><biologic marker><biomarker><case report><catalog><clinical predictive model><complementation><computer based prediction><corona virus><coronavirus disease 2019><coronavirus disease 2019 associated morbidity><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health 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response><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><long-term sequelae><mAbs><model of animal><monoclonal Abs><multiomics><multiple omics><nCoV2><open source><panomics><pathogen><predictive modeling><response><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><single cell next generation sequencing><single cell sequencing><social role><technological innovation><transcriptomics><validations><variants of concern><viral infection><virus genetics><virus genome><virus infection><virus-induced disease>