Grant: CIHR Fellowship

Vaccines are the most successful medical intervention existing to date. Still, we are lacking efficient and broadly accepted vaccines for newborns against many infectious diseases. This is the most vulnerable demographic, largely due to an inexperienced immune system, and they rely on the transfer of immunity from their mothers. This maternal protection is achieved in part through antibodies, transferred to the neonate through the placenta pre-birth (Immunoglobulin (Ig)G) and via breastmilk after birth (IgG and IgA). Transferred IgA protects mainly through blocking the pathogen from entering the offspring's system, whereas IgG can be actively taken up through the gut wall via the neonatal Fc Receptor (nFcR), potentially shuttling bound pathogen material as an immune complex (IC, antigen:IgG) into the baby's system. Oral vaccination is relatively safe and easy to administer, but to date only two are licensed for babies - Rotavirus (RV) and Pertussis - successful vaccines of which we do not understand the mode of action in any detail. Using our well-established murine RV intestinal infection model, we studied the role of pre-existing maternal immunity in response to neonatal oral RV exposure, mimicking the oral attenuated-live vaccine. We found that maternal antibodies in breastmilk protect the offspring from infection, but also educate the offspring's own immune system to boost long-term immunity, challenging the current theory that maternal antibody might negatively interfere with vaccination efficiency. I will explore the mechanism behind this double layer of protection and engineer antibodies for increased uptake via the nFcR to induce strong adaptive immunity in the absence of infection. My goal is to improve vaccine formulas to enhance vaccine outcomes improving long-term protection. I will use human intestinal organoids to examine translatability of the findings as well as the murine RV infection model to decipher the mechanism behind our observation.