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Principal Investigator: Boris Dominik Juelg
Organization: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Fiscal Year: 2024
Award: $600,000
Funding agency: National Institute of Allergy and Infectious Diseases
Project 2: Summary
While traditionally regarded as a generalized tolerogenic state, emerging data suggest that pregnancy is
far from a simple anti-inflammatory shift but is characterized by dramatic shifts from inflammation to tolerance
over the course of pregnancy, to accommodate changes in the fetus. These dramatic shifts in the immune
response are under exquisite chronological control and are accompanied by significant changes in ex vivo
cellular responsiveness. However, how these immunological dynamics control the systemic immune response
remains incompletely understood. Accumulating data point to immune vulnerabilities during pregnancy, with
enhanced susceptibility to respiratory viral infectious including influenza and SARS-CoV-2 as well as dampened
vaccine induced immunity. However, how the evolving immune response over gestation affects the overall
response to vaccination, how it influences the quality of antibody transfer to infant, as well as how these changes
may influence durability of protection after birth remains incompletely understood. Yet, we are at a unique
moment in history, where a number of novel vaccine platforms are being rolled out to pregnant women in the
battle against SARS-CoV-2. In addition to the currently EUA approved vaccines, additional vaccines will emerge,
enabling the comparison of mRNA, adenoviral vectors, and adjuvanted protein platform comparisons, all of which
will be recommended throughout pregnancy to drive immunity in largely naïve pregnant women and their infants.
However, the ability of vaccines to boost immunity in previous infected mothers as well as to boost immunity in
the future in previously immunized mothers using heterologous prime/boosting strategies will provide a unique
opportunity to begin to define the vaccine strategies able to maximally drive immunity over gestation. Moreover,
linked to recommended booster vaccines to Influenza and Pertussis, this consortium will have a rare opportunity
to contrast immune responses induced by recall/de novo, homologous/heterologous, and distinct vaccine
platforms across the 4 trimesters of pregnancy, providing an opportunity to generate the foundational data on
immune programming of T and B cell immunity. Using both proprietary and established systems immunology
profiling tools, the consortium will focus in Project 2 on mapping the broad antibody-OME and vaccine induced
humoral immune responses as well as to profile the SARS-CoV-2-, Influenza- and Pertussis-specific B and T
cell transcriptome. These data will form the basis of the first pregnant Vaccine-OME to guide next generation
vaccine and therapeutic design to selectively leverage and maximize protection across the maternal:fetal dyad.
Terms: <0-4 weeks old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><Ad vector><Adenoviral Vector><Adenovirus Vector><Adjuvant><Affect><Allografting><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Antibodies><Antibody titer measurement><Antigens><Atlases><Awareness><B blood cells><B cell><B cells><B pertussis infection><B-Cells><B-Lymphocytes><B-cell><B. pertussis infection><Biochemical><Birth><Bordetella pertussis infection><Breast Milk><Breastmilk><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 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 vaccine><COVID-19 virus><COVID-19 years><COVID19 virus><Case Fatality Rates><Cells Placenta-Tissue><Cellular Assay><Cellular Immune Function><Cessation of life><Chronology><Clinical><CoV-2><CoV2><Communicable Diseases><Data><Data Analyses><Data Analysis><Death><Disease><Disorder><Eligibility><Eligibility Determination><Emergencies><Emergency Situation><Fetal Growth><Fetus><Future><Generalized Growth><Genetic><Gestation><Grippe><Growth><H1N1><H1N1 Virus><Health Care Providers><Health Personnel><Healthcare Providers><Healthcare worker><History><Human Milk><Human Mother's Milk><Immune><Immune response><Immunes><Immunity><Immunization><Immunize><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Infant><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammation><Inflammatory><Influenza><Influenza A Virus, H1N1 Subtype><Link><Mammary Gland Milk><Maps><Maternal-fetal medicine><Messenger RNA><Morbidity><Morbidity - disease rate><Mother's Milk><Mothers><Newborn Infant><Newborns><Normal Placentoma><Parturition><Pertussis><Phase><Phenotype><Placenta><Placenta Embryonic Tissue><Placental Development><Placentation><Placentome><Population><Predisposition><Pregnancy><Pregnancy Trimesters><Pregnant Women><Property><Proteins><Protocol Screening><R-Series Research Projects><R01 Mechanism><R01 Program><RNA vaccine><RNA-based vaccine><Race><Races><Recommendation><Recording of previous events><Research Grants><Research Project Grants><Research Projects><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 vaccine><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Safety><Sampling><Serology><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 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><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 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Shapes><Specialist><Susceptibility><Syndrome><System><T cell response><T-Cells><T-Lymphocyte><Therapeutic><Tissue Growth><Vaccination><Vaccination acquired immunity><Vaccination induced immunity><Vaccine Design><Vaccines><Viral><Vulnerable Populations><Whooping Cough><Woman><Work><Wuhan coronavirus><adaptive immune response><adeno vector><adenovector><antibody titering><antibody transfer><booster dose><booster shot><booster vaccine><cell assay><co-morbid><co-morbidity><comorbidity><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 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 vaccine><coronavirus disease-19 virus><data interpretation><deploy vaccines><design><designing><distribute vaccines><expectant mother><expecting mother><experience><fetal><global gene expression><global transcription profile><hCoV19><health care personnel><health care worker><health provider><health workforce><healthcare personnel><hemodynamics><histories><host response><immune function><immune reconstitution><immune system response><immunogen><immunogenic><immunoresponse><implantation><infected with B pertussis><infected with B. pertussis><infected with Burkholderia pertussis><infection risk><intervention design><intra-uterine growth><intrauterine growth><mRNA><mRNA vaccine><mRNA-based vaccine><maternal milk><medical personnel><mortality><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neonate><new vaccines><newborn child><newborn children><next generation><next generation vaccines><novel><novel vaccines><ontogeny><pandemic><pandemic disease><phase 3 trial><phase III trial><pregnant><pregnant mothers><racial><racial background><racial origin><rational design><respiratory><response><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><success><therapy design><thymus derived lymphocyte><tool><transcriptome><treatment design><treatment provider><vaccine acquired immunity><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 antibodies><vaccine associated immunity><vaccine boost><vaccine candidates against SARS-CoV-2><vaccine deployment><vaccine distribution><vaccine for novel coronavirus><vaccine induced antibodies><vaccine platform><vaccine response><vaccine responsiveness><vaccine roll-out><vaccine rollout><vaccine safety><vaccine strategy><vaccine-induced antibodies><vaccine-induced immunity><vaccine-induced protection><vaccine-induced response><vaccines preventing COVID><vaccines to prevent COVID><vulnerable group><vulnerable individual><vulnerable people>