Penn Medicine, Philadelphia: $12 Million Grant Propels Research of Immune Systems of Pregnant Individuals

To reveal how the immune system may drive health and disease in pregnant people and better understand how to best leverage vaccines to ensure maternal and fetal protection from infectious disease, a team of researchers has been awarded a five-year, over $12 million grant from the National Institute of Allergy and Infectious Diseases’ Human Immunology Project Consortium (HIPC) for the promotion of multidisciplinary investigations and the advancement of maternal health. The grant recipients include faculty from the Perelman School of Medicine at the University of Pennsylvania, Massachusetts General Hospital (MGH)/Harvard Medical School, and MIT. Ultimately, the researchers hope their work leads to new interventions that improve the lives of mothers and their babies.

Michal Elovitz, MD, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at Penn; Galit Alter, PhD, a professor of Medicine at Harvard Medical School and group leader at the Ragon Institute; Douglas A. Lauffenburger, PhD, the Ford Professor of Engineering at MIT; and Andrea Edlow, MD, MSc, a Maternal-Fetal Medicine specialist at MGH and associate professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School, will lead investigations focused on uncovering the sequence of immune system changes in pregnant people and the development of the fetal immune system.

This project is the first time a HIPC project will support research into the immunology of pregnancy. Findings from the research will create a “Pregnancy Immune Atlas,” a platform which would not only provide insight into the optimal moments for vaccinations but would also reveal how variations in the immune system during pregnancy may lead to different health conditions.

“COVID-19 revealed what many of us taking care of pregnant individuals already knew—that there is insufficient understanding of how the immune system works in pregnancy and that the exclusion of pregnant people in both translational and clinical research has not protected them but, in fact, harmed them,” Elovitz said. “Our goal with this research is to map out what the immune system looks like and how it functions across pregnancy—so that we can have a platform on which to understand how to best utilize maternal vaccination and to help improve outcome from pregnancy complications driven by changes in the maternal immune system.”

This research collaborative marks a continued relationship between the Ragon Institute of MGH, MIT, and Harvard, and Penn. That includes a study last year published in the American Journal of Obstetrics & Gynecology that found the mRNA COVID-19 vaccine offered immune protection to the virus for pregnant and lactating women at greater levels than prior infection. It also found that immune protection was transferred to neonates through the placenta and through breast milk.

“We are in the midst of a scientific revolution in immunology due to the application of systems biology to all facets of human health and disease, yet pregnancy represents one of the most unique immunological states in humans that is so poorly understood,” said Alter. “It is truly exciting that the NIH HIPC program has moved to include our Maternal ’Omics to Maximize Immunity (MOMI) consortium in the systems biology family for the first time.”

“The COVID-19 pandemic and development of numerous COVID-19 vaccine platforms provide an unprecedented opportunity to understand the trimester-specific maternal immune profile, at baseline and in response to new and familiar vaccines,” said Edlow. “We want to use cutting-edge technologies to create a uniquely comprehensive scientific picture of pregnancy immunity, but also to generate pragmatic knowledge that can be rapidly translated to optimize care for pregnant patients and their developing fetuses.”