Impact of cytomegalovirus infection on heterologous vaccine responsiveness

Persistent infection with cytomegalovirus (CMV) induces massive cellular immune responses in humans. Over time, CMV infection leads to the accumulation of differentiated oligoclonal αβ T cells, NK cells and γδ T cells, a phenomenon often referred to as memory inflation. This infection also contributes to the decline of immune resources and an increased inflammatory status with advanced age, potentially affecting immune responses to unrelated antigens. Here, we discuss studies that highlight a potential influence of CMV infection on heterologous vaccine responsiveness in various contexts, including different types of vaccines, immune responses analysed and the age of vaccine recipients. These studies indicate that CMV infection is associated with reduced primary immune responsiveness to vaccination, particularly in older adults, with notable effects on CD4⁺ T cell and antibody responses. The impact of CMV on vaccine immunogenicity likely stems from the virus amplifying age- or pathology-related alterations in the immunological and inflammatory environment of persistently infected individuals. Consequently, CMV infection may reduce the efficacy of certain vaccinations, particularly in vulnerable populations.This article is part of the discussion meeting issue 'The indirect effects of cytomegalovirus infection: mechanisms and consequences'.