Proteins in Focus: The Impact of Age on Antibody-, CD4+ T Cell-, and Macrophage Immunity targeting the Proteome of Streptococcus pneumoniae

Streptococcus pneumoniae is a bacterial microorganism that causes serious infections, particularly in young children and older adults. It relies on two main types of factors to do this: a sugar-based outer coating and a large set of proteins. While immune responses to the sugar coating—of which nearly hundred serotypes exist—are well studied, current vaccines only target certain serotypes, leaving gaps in protection. In contrast, less is known about how the body acquires responses to serotype-independent bacterial proteins, especially in older adults. This thesis examines how aging affects the body's ability respond to proteins of S. pneumoniae. Older adults contain fewer antibodies in both their saliva and blood than younger adults, and antibodies to some proteins are lost more than others. Additionally, the immune cells that help fight infections, called CD4+ T cells, are less active in older individuals. They also produce lower amounts of key signaling molecules, shown to impair the body’s macrophages to kill the bacteria. At the same time, there are more regulatory T cells in older individuals, lowering the efficiency of their immune response. Overall, the findings show that aging affects several aspects of the immune system's response to the proteins of S. pneumoniae. This could explain why older adults become more vulnerable to infections. Since current vaccines do not cover all serotypes, understanding these age-related shifts in immunity to bacterial proteins could support the development of universal vaccines and strategies, ultimately enhancing protection against pneumococcal disease including in older adults and other high-risk groups.