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Principal Investigator: Andrea Goldberg Edlow
Organization: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Fiscal Year: 2022
Award: $470,797
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: <2019-nCoV vaccine><Address><Adenoviridae><Adenoviruses><Adjuvant><Age><Antigens><Area><Assay><Atlases><B pertussis infection><B. pertussis infection><BMI><BMI percentile><BMI z-score><Bioassay><Biologic Assays><Biological Assay><Blood Plasma><Body mass index><Bordetella pertussis infection><CITE sequencing><CITE-seq><CITEseq><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 negative><COVID-19 pandemic><COVID-19 public health crisis><COVID-19 vaccination><COVID-19 vaccine><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 negative><COVID19 pandemic><COVID19 public health crisis><COVID19 vaccination><COVID19 vaccine><Cell Body><Cells><Cellular Assay><Cellular Indexing of Transcriptomes and Epitopes by Sequencing><Characteristics><Chromatin><Clinical><Collaborations><Complex><Data><Data Analyses><Data Analysis><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 response><Immune system><Immunes><Immunity><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><In Vitro><Infant><Infection><Inflammation><Influenza><Influenza Vaccines><Infrastructure><Knowledge><Maps><Maternal Immunity><Maternally-Acquired Immunity><Messenger RNA><Metabolic Diseases><Metabolic Disorder><Metagenomics><Modern Man><Mothers><PBMC><Peripheral Blood Mononuclear Cell><Pertussis><Pertussis Vaccine><Plasma><Plasma Serum><Population><Pregnancy><Pregnancy Trimesters><Pregnant Women><Proteins><Proteome><Proteomics><Quetelet index><R-Series Research Projects><R01 Mechanism><R01 Program><Recording of previous events><Research Grants><Research 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response><ages><allergic/immunologic body system><allergic/immunologic organ system><antibody receptor><antibody transfer><balance><balance function><booster dose><booster shot><booster vaccine><cell assay><cellular indexing of transcriptomes and epitopes by single cell sequencing><cohort><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><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 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generation><novel><novel pathogen><pandemic><pandemic disease><pathogen><placental transfer><pregnant mothers><prospective><receptor expression><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 COVID19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against COVID19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><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 development><vaccine for novel coronavirus><vaccine platform><vaccine response><vaccine responsiveness><vaccine strategy><vaccine-induced response>