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Principal Investigator: Maria Virginia Pascual
Organization: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
Fiscal Year: 2024
Award: $1,688,409
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
Viral respiratory infections are responsible for major morbidity and mortality in early life. Infants account for a
significant proportion of influenza hospitalizations and are considered a top high-risk group. In addition to the
acute morbidity, initial immune responses to influenza shape/imprint the immune system and affect subsequent
responses to influenza infections and vaccinations, which tend to induce humoral responses skewed towards
epitopes present in the first influenza antigen encountered. In contrast, SARS-CoV-2 infection in infants is
generally mild and less severe than in older individuals. This is remarkable and suggests that there are unique
features on how the infant immune system responds to SARS-CoV-2, compared to its responses against other
respiratory viruses, that can be leveraged to improve our understanding of early life immunity.
On the basis of these observations, we hypothesize that early life viral respiratory infections elicit virus-specific
immune responses that lead to distinct immune developmental trajectories. To address this hypothesis, we will
compare three longitudinal cohorts: i) infants infected with SARS-CoV-2; ii) infants infected with influenza virus;
and as reference iii) healthy infants with none of those two infections. After acute infection children will be
followed longitudinally for three years and immune responses assessed in the context of influenza and COVID-
19 vaccinations.
We designed two integrated research projects, supported by three cores. Project 1 will define: 1) the differences
of blood transcriptional immune signatures in infants with SARS-CoV-2 versus infants with influenza infection;
2) the magnitude, immunodominance pattern and breath of the antibody responses to influenza virus and
evolution of antibody responses to SARS-CoV-2; and 3) perform high-throughput longitudinal evaluation of B
cell responses to influenza and SARS-CoV-2. Project 2 will: 1) Assess the blood cell composition, transcriptome
and epigenome in response to influenza and SARS-CoV-2 infection occurring in the first six months of life at the
single cell level; and 2) Characterize the PBMC phenotype/cell composition, transcriptome and epigenome in
response to vaccination against influenza and SARS-CoV-2.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><ATAC sequencing><ATAC-seq><ATACseq><Acute><Address><Affect><Antibodies><Antibody Response><Antibody titer measurement><Antigenic Determinants><Antigens><Assay for Transposase-Accessible Chromatin using sequencing><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding Determinants><Blood><Blood Cells><Blood Reticuloendothelial System><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CITE sequencing><CITE-seq><CITEseq><COVID-19 infection><COVID-19 vaccination><COVID-19 vaccine><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Cell Body><Cell Nucleus><Cell surface><Cells><Cellular Assay><Cellular Indexing of Transcriptomes and Epitopes by Sequencing><Child><Child Youth><Children (0-21)><CoV-2><CoV2><Development><Disease><Disorder><Drop-seq><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Epitopes><Evaluation><Evolution><Exposure to><Flu vaccination><Gene Transcription><Genes><Genetic Transcription><Grippe><Hospital Admission><Hospitalization><Immune><Immune response><Immune system><Immunes><Immunity><Immunologic Subtyping><Immunological response><Immunophenotyping><Infant><Infection><Influenza><Influenza Virus><Influenza immunization><Influenza vaccination><Learning><Life><Long-term cohort><Longitudinal cohort><Longterm cohort><Morbidity><Morbidity - disease rate><Multivariate Analyses><Multivariate Analysis><Nucleus><Older Population><PBMC><Participant><Pattern><Pattern recognition receptor><Peripheral Blood Cell><Peripheral Blood Mononuclear Cell><Phenotype><Production><Prophylactic vaccination against influenza><R-Series Research Projects><R01 Mechanism><R01 Program><RNA Expression><Research Grants><Research Project Grants><Research Projects><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><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 CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><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 infection><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Shapes><Specificity><T8 Cells><T8 Lymphocytes><Transcription><Vaccination><Vaccines><Viral Diseases><Viral Respiratory Tract Infection><Virus><Virus Diseases><Wuhan coronavirus><acute infection><antibody titering><assay for transposase accessible chromatin followed by sequencing><assay for transposase accessible chromatin seq><assay for transposase accessible chromatin sequencing><assay for transposase-accessible chromatin with sequencing><cell assay><cellular indexing of transcriptomes and epitopes by single cell sequencing><coronavirus disease 2019 infection><coronavirus disease 2019 vaccination><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19 vaccine><coronavirus disease-19 virus><cytokine><design><designing><developmental><droplet sequencing><epigenetically><epigenome><flu immunisation><flu infection><flu virus infection><global gene expression><global transcription profile><hCoV19><high dimensional data><high risk group><high risk individual><high risk people><high risk population><host response><immune system response><immunogen><immunophenotype><immunoresponse><imprint><improved><infant infection><infected infant><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with flu><infected with flu virus><infected with influenza><infected with influenza virus><infected with severe acute respiratory syndrome coronavirus 2><influenza infection><influenza virus infection><influenza virus vaccination><influenzavirus><kids><mortality><multidimensional data><multidimensional datasets><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><older groups><older individuals><older person><respiratory virus><response><seasonal flu><seasonal influenza><transcriptome><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccination against influenza><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine candidates against SARS-CoV-2><vaccine for novel coronavirus><vaccines preventing COVID><vaccines to prevent COVID><viral infection><viral respiratory infection><virus infection><virus-induced disease><youngster>