Human-Relevant Microphysiological System to De-Risk Vaccine Development in Pregnancy

Vaccines that use messenger RNA (mRNA), a biological instruction molecule, packaged inside tiny fat-like particles called lipid nanoparticles have changed how we prevent infectious diseases. COVID-19 mRNA vaccines saved millions of lives worldwide. However, pregnant people are often left out of early vaccine testing because it is hard to study both how well a vaccine works and whether it is safe for the fetus using current lab and animal models. These models do not reliably reflect human pregnancy or show whether vaccine particles can pass through the placenta. This slows the development and approval of vaccines for use in pregnancy. We will build a new human-based testing tool called an "organ-on-a-chip." These are small lab devices that grow living human cells under realistic flow conditions to mimic how tissues behave in the body. Our platform will connect two chips: one that models the human immune response to vaccination, and one that models the placenta, which controls what passes from mother to fetus. Linking them lets us study vaccine responses and safety at the same time. With this system, we will measure how strongly vaccines trigger protective immune responses, whether helpful antibodies reach the fetal side, and whether vaccine particles themselves cross the placental barrier or cause stress to placental cells. We will first test the platform using well-known COVID-19 mRNA vaccines, then use it to study new influenza mRNA vaccines and different doses and formulations. This project will create a practical new way to test vaccines for pregnancy, helping researchers and vaccine developers design safer and more effective maternal vaccines and better protect pregnant people and newborns.