Document text
Principal Investigator: Andrea Goldberg Edlow
Organization: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Fiscal Year: 2024
Award: $669,960
Funding agency: National Institute of Allergy and Infectious Diseases
Project 1: Summary
The COVID-19 pandemic has revolutionized our ability to decode the rules of maternal immunity. There is a
significant gap in knowledge regarding innate and adaptive immune responses over the course of pregnancy
and how trimester-specific perturbations in the maternal immunological signature might manifest in attributable
risk or benefit to the maternal-fetal dyad. The COVID-19 vaccines and their real-world use by pregnant women
present a unique opportunity to define the baseline, trimester-specific immune signature, and to examine the
maternal immune response after in vivo perturbation with both de novo (never before seen by the immune
system) and recall (boosted responses such as influenza and pertussis) vaccines across the trimesters of
pregnancy. In Project 1 in the Maternal ‘Omics to Maximize Immunity (MOMi) consortium, we propose to
apply a multi-‘OMICs approach to deeply and comprehensively capture shifts in the maternal immune
response before and after maternal immunization across pregnancy. We will profile maternal peripheral
blood mononuclear cells, plasma, placental cell isolates, and stool from pre- and post-maternal vaccination,
using single cell RNA-Seq (scRNA-Seq), Assay for Transposase-Accessible Chromatin with high-throughput
sequencing (scATAC-Seq), Cellular Indexing of Transcriptomes and Epitopes by Sequencing (scCITE-Seq),
proteomics, metabolomics, and metagenomics, and integrate all data through the Data Management and
Analysis Core (DMAC). In collaboration with Project 2, the ultimate goal is to define maternal immunity
longitudinally across pregnancy trimesters in the normal baseline and vaccinated state, in order to build the most
comprehensive Pregnancy Immune Atlas of innate and adaptive immune profiling across the maternal-fetal
dyad. We will examine how the cellular transcriptome, microbiome, metabolome, and proteome shifts over the
course of pregnancy, and how they are modified in response to different vaccine platforms (mRNA, adenovirus,
adjuvanted protein) and types (de novo versus recall), providing a unique opportunity to profile the maternal
immune response with unprecedented resolution. This detailed map of pregnancy immunity will generate critical
data to open previously unrecognized therapeutic windows in this unusual and understudied area of human
immunology.
Terms: <0-11 years old><2019-nCoV vaccine><Address><Adenoviridae><Adenoviruses><Adjuvant><Age><Antigens><Area><Assay><Atlases><B pertussis infection><B. pertussis infection><B. pertussis vaccine><BMI><BMI percentile><BMI z-score><Bioassay><Biological Assay><Blood Plasma><Body mass index><Bordetella pertussis infection><Bordetella pertussis vaccine><CITE sequencing><CITE-seq><CITEseq><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 negative><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 vaccination><COVID-19 vaccine><COVID-19 years><COVID19 negative><Cell Body><Cell Isolation><Cell Segregation><Cell Separation><Cell Separation Technology><Cells><Cells Placenta-Tissue><Cellular Assay><Cellular Indexing of Transcriptomes and Epitopes by Sequencing><Characteristics><Child><Child Youth><Children (0-21)><Chromatin><Clinical><Collaborations><Complex><Data><Data Analyses><Data Analysis><Decidua Basalis><Disease><Disorder><Enrollment><Ensure><Equilibrium><Fc Receptor><Feces><Functional Metagenomics><Future><GI microbiome><Gestation><Goals><Grippe><High-Throughput Nucleotide Sequencing><High-Throughput Sequencing><History><Human><Immune><Immune Tolerance><Immune response><Immune system><Immunes><Immunity><Immunochemical Immunologic><Immunologic><Immunologic Tolerance><Immunological><Immunological response><Immunologically><Immunologics><Immunology><In Vitro><Infant><Infection><Inflammation><Influenza><Influenza Vaccines><Infrastructure><Innate Immune Response><Knowledge><Maps><Maternal Immunity><Maternal Mortality><Maternal placenta><Maternally-Acquired Immunity><Messenger RNA><Metabolic Diseases><Metabolic Disorder><Metagenomics><Modern Man><Mothers><Normal Placentoma><PBMC><Peripheral Blood Mononuclear Cell><Pertussis><Pertussis Vaccine><Placenta><Placenta Embryonic Tissue><Placentome><Plasma><Plasma Serum><Population><Pregnancy><Pregnancy Trimesters><Pregnant Women><Proliferating><Proteins><Proteome><Proteomics><Quetelet index><R-Series Research Projects><R01 Mechanism><R01 Program><Recording of previous events><Research Grants><Research Project Grants><Research Projects><Resolution><Reticuloendothelial System, Serum, Plasma><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 negative><SARS-CoV-2 pandemic><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><Sampling><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Shapes><Shotguns><Systems Biology><Therapeutic><Thesaurismosis><Time><Transposase><Vaccinated><Vaccination><Vaccine Design><Vaccine against B. pertussis><Vaccine against Bordetella pertussis><Vaccine against pertussis><Vaccines><Whooping Cough><Woman><Work><adaptive immune response><ages><antibody receptor><antibody transfer><attributable risk><balance><balance function><booster dose><booster shot><booster vaccine><cell assay><cell sorting><cell type><cellular indexing of transcriptomes and epitopes by single cell sequencing><cohort><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 negative><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 vaccination><coronavirus disease 2019 vaccine><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 vaccine><data integration><data interpretation><data management><develop a vaccine><develop vaccines><development of a vaccine><digestive tract microbiome><early pregnancy><emerging pathogen><enroll><enteric microbiome><expectant mother><expecting mother><experiment><experimental research><experimental study><experiments><fetal><flu vaccine><flu virus vaccine><gastrointestinal microbiome><global gene expression><global transcription profile><gut microbiome><gut-associated microbiome><healthy pregnancy><high dimensionality><histories><host response><immune system response><immune system tolerance><immune unresponsiveness><immunogen><immunological paralysis><immunoresponse><in vivo><infected with B pertussis><infected with B. pertussis><infected with Burkholderia pertussis><influenza virus vaccine><insight><intestinal biome><intestinal microbiome><kids><mRNA><maternal death><maternal immune system><maternal immunization><maternal vaccination><metabolism disorder><metabolism measurement><metabolome><metabolomics><metabonome><metabonomics><metagenome sequencing><metagenomic sequencing><microbial><microbiome><mother immune system><multidisciplinary><multiomics><multiple omics><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><neonate><new pathogen><next generation><novel><novel pathogen><pandemic><pandemic disease><panomics><pathogen><placental transfer><pregnant mothers><prospective><receptor expression><resolutions><response><scRNA-seq><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 negative><sex><shot gun><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><stool><therapeutic agent development><therapeutic development><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><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 against flu><vaccine against influenza><vaccine boost><vaccine candidates against SARS-CoV-2><vaccine development><vaccine for novel coronavirus><vaccine platform><vaccine response><vaccine responsiveness><vaccine strategy><vaccine-induced response><vaccines preventing COVID><vaccines to prevent COVID><youngster>