388 - Developing a measles maternal antibody mouse model using mRNA-lipid nanoparticles

Publication Number: 2377.388

Sue-Ling M. Gannon, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Jordan T. Ort, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Ross N.. England, Childrens Hospital of Philadelphia, Havertown, PA, United States

Background: Maternal antibodies (matAbs) protect infants against infection but also inhibit immune responses to most vaccines, delaying effective immunization in early life. This limitation is particularly important for measles, which continues to cause over 100,000 child deaths annually and accounts for >2% of global mortality in children under five. mRNA-lipid nanoparticle (LNP) vaccines have shown potential to overcome maternal antibody interference (MAI) in some models, but the mechanisms and relevance to measles remain poorly understood.

Objective: To establish a mouse model of measles maternal antibody interference to test whether mRNA-LNP vaccination can elicit immune responses despite the presence of matAbs.

Design/Methods: Female C57BL/6 mice were immunized intramuscularly with 1e5 pfu of measles virus Edmonston strain (MeV Edm) at time of mating. Measles H-specific IgG was quantified in dams and offspring by ELISA to determine placental transfer efficiency and antibody decay kinetics. 3-week-old pups (lacking matAbs) were vaccinated with either MeV Edm (1e5 – 1e7 pfu) or an mRNA-LNP encoding the membrane-bound H glycoprotein (0.3 – 1 µg). H-specific serum antibody titers were measured at 0, 1, and 4 weeks post-vaccination.

Results: MeV Edm-immunized dams generated high-titer MeV H-specific IgG, which was transferred to all pups with a placental transfer ratio of 0.43 (95% CI 0.31 – 0.61). Antibody levels declined predictably over time, defining a measurable window for MAI studies. In naïve pups, MeV Edm doses of 1e5, 1e6, 1e7 pfu elicited geometric mean titers (GMTs) of 1,285, 4,425, and 4,825, respectively (p < 0.05 vs control). mRNA-LNP doses of 0.3 and 1 µg elicited GMTs of 1,695 and 23,332, respectively (p < 0.05 vs control).

Conclusion(s): These data define measles maternal antibody transfer and decay and immunogenic dosing for live-attenuated and mRNA-LNP measles vaccines in weanling pups necessary for the establishment of a measles mRNA-LNP maternal antibody mouse model. Ongoing studies will determine whether mRNA-LNP vaccination can overcome MAI and elucidate immune mechanisms enabling MAI breakthrough. These findings will guide the rational development of next-generation vaccines for newborns and young infants.