mRNA-LNP Vaccines Can Overcome Maternal Antibody Inhibition and Enable de novo IgG Resposnes in Mouse Pups 4796

Abstract Description Introduction Maternal antibody (matAb) may inhibit vaccine responses in early life. As children younger than 6 months have increased risk for severe respiratory disease, effective immunization strategies to prevent infant morbidity and mortality are needed. We developed a mouse immunization model to study pup vaccine elicited humoral responses within the context of vaccine specific matAb. Methods Pups were immunized with PBS or 5ug of SARS-CoV-2 mRNA-LNP vaccine, mRNA-1273, via intramuscular injection. Peripheral blood and spleens were collected at various timepoints p.i. We measured Spike specific IgG in mouse pups exposed or unexposed to vaccine specific maternal IgG. Results Spike specific maternal IgG (matIgG) is detectable at high levels in pup peripheral blood. MatIgG wanes to below the positive cutoff by three weeks post immunization (p.i.), coinciding with peak vaccine elicited IgG levels in unexposed pups. Pups exposed to matAb have a lower level of Spike specific IgG compared to unvaccinated pups at two weeks p.i. however by three weeks p.i. pups exposed to matAb reach comparable anti-Spike IgG levels. Conclusions Using SARS-CoV-2 mRNA vaccines as a model, we found that matAb exposed or unexposed pups reach comparable vaccine specific IgG levels. These findings indicate that the mRNA-LNP platform may provide a vaccine option in early life. Funding Sources Thrasher Pediatric Research Fund Topic Categories Vaccines and Immunotherapy (VAC)