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Massachusetts Institute of Technology

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Grant title: Maternal ‘Omics to Maximize Immunity (MOMi)

Grant number: 1U19AI167899

Lead institution: Massachusetts Institute of Technology, Massachusetts General Hospital, Mount Sinai Hospital

Center PI(s): Prof. Douglas Lauffenburger, Dr. Andrea Edlow, Dr. Michal Elovitz, Dr. Boris Juelg

From the moment of fertilization to birth, the maternal immune system evolves, adapts, and supports the growth of a fetal allograft that ultimately perpetuates the human race. Immunological changes throughout a pregnancy play a key deterministic role in the success of the pregnancy. While pregnancy was historically regarded as a simple shift towards tolerance, emerging immunological data point to remarkable dynamic changes during pregnancy. The pregnancy immunome must protect the fetus from a maternal attack while at the same time it must afford the maternal-fetal dyad protection from invading pathogens. The health of the mother and the fetus requires that these two opposing immunological tasks work in concert. Thus collectively, pregnancy marks a whirlwind of immune adaptations that render the pregnant immune system a truly unique immunologic marvel. Despite our growing appreciation for these highly controlled dynamic shifts, the precise mechanisms that lead to optimal pregnancy health, profoundly impacting both mother and fetus, are incompletely understood, delaying the development of targeted therapies for this population. Capitalizing on this unique moment in vaccine history, with the introduction of several novel-vaccine platforms for SARS-CoV-2, the consortium will build a Pregnancy Immune Atlas via the application of high-density immunological profiling technologies to deeply and comprehensively dissect the overall changes that occur across pregnancy and how the immune system, as a collective, responds to in vivo perturbations with vaccines. Using both de novo vaccine induced immune responses and booster vaccination, the consortium will capture overall changes in the pregnant ImmunOME as well as shifts in the pregnant AdaptOME to fully capture the immunological mechanisms that govern the balanced growth of the fetus and battle of the maternal:fetal dyad against invading pathogens. Thus, together the Maternal ‘Omics to Maximize Immunity (MOMi) consortium seeks to build the foundational data to advance our knowledge of natural tolerance, fertility, shifts in immunity during pregnancy to better understand this evolutionary marvel required for the perpetuation of the human species.