The maternal antibody paradox: Characterising mechanisms and devising solutions for rotavirus vaccination (360G-Wellcome-211138_Z_18_Z)

Maternal antibodies (MA) are transferred to fetus and infant via the placenta and through breast milk, providing protection against pathogens when the immune response is immature. However, MA also suppress the development of B cell responses to pathogens via mechanisms that are not well defined. MA can therefore result in poor vaccine performance in the infant, placing them at risk against potentially life-threatening pathogens such as rotavirus. Rotavirus infection poses a substantial threat to human health globally. The virus is a major cause of acute gastroenteritis in young children, resulting in ~215,000 deaths each year. Rotavirus vaccines have recently been applied with great success in developed countries, however it is unknown why rotavirus vaccines are much less effective in low-income countries. Whilst malnutrition and the gut microbiome may contribute to poor vaccine efficacy, interference by MA is also considered to be a major prohibitive factor. This study aims to unravel the mechanisms by which MA limit development of effective antibody responses to rotavirus vaccination in infants. This project also aims to translate mechanistic results into rational design of improved vaccines. This work has the potential to generate vaccines that induce protection against rotavirus in younger children across all economic areas.