Project Details

Evaluating mRNA-lipid nanoparticle and adjuvants in a measles maternal antibody model

Ross England, MD, PhD

Summary

BACKGROUND: Maternal antibodies (matAbs) limit the effective vaccination of newborns and young infants with most vaccine types and delay initiation of vaccination against measles, a disease that continues to account for > 2% of deaths of children younger than 5 years. I and my colleagues have shown that mRNA-lipid nanoparticle (LNP) vaccines can overcome this maternal antibody interference (MAI) to some vaccines in mice. GAP: Factors that allow mRNA-LNP vaccines to overcome MAI and the degree to which these could be used to augment other vaccine types are not understood. HYPOTHESIS: My central hypothesis is that lipid nanoparticles (LNP) provide adjuvant activity that can allow mRNA-LNP to overcome MAI. I hypothesize that mRNA-LNP and LNP-adjuvanted typical measles vaccines will elicit Ab responses in mice despite matAbs. METHODS: I will vaccinate mouse pups (with or without measles matAbs) with a mRNA-LNP measles vaccine or a typical live attenuated measles vaccine with or without LNP adjuvant. I will quantify matAb placental transfer efficiency and decay using ELISA, de novo Abs in serum using ELISA and MV neutralization assays and measles-specific memory B cells and long-lived plasma cells in spleens and bone marrow using flow cytometry. RESULTS: Pending. IMPACT: The findings from the completion of this research project will help to determine whether mRNA-LNP or LNP-adjuvanted vaccines can overcome maternal antibody interference seen with other measles vaccines, leading to knowledge that can help guide rational vaccine design for infants and, long-term, decrease illness and death due to measles. Website Link: https://www.chop.edu/doctors/england-ross-n