Grant: Project Grant

It has been well-documented that one's first influenza virus infection has a lasting influence on how one responds to future infections. This has concept has been termed "original antigenic sin (OAS)" or "antigenic imprinting". OAS/antigenic imprinting can have either beneficial or detrimental consequences, depending on the situation. Despite extensive descriptive data documenting occurrences of OAS/ antigenic imprinting, very little is known mechanistically about how these phenomena occur. Furthermore, most of what is known about OAS/imprinting in humans comes from historical studies wherein the first exposure to influenza was by acute infection. However, many children are now first exposed to influenza by vaccination. The number of influenza vaccine types continues to expand, and there is strong evidence that the specific nature one's first exposure (ie. infection, split vaccine, live-attenuated vaccine, etc.) has a strong influence on the extent to which OAS/imprinting occur. Using a unique longitudinal cohort of children, we will determine how the nature of a child's first exposure to influenza virus affects OAS/imprinting. We will then perform mechanistic investigations to define the factors that are responsible for the development of OAS/imprinting using mouse models. This information will inform which vaccine formulations should be administered to children, and those vaccine formulations that are most effective for eliciting strain-specific or cross-reactive responses.