Overcoming T cell-mediated immunopathology to achieve safe RSV vaccination

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in young children. Premature infants, immunocompromised individuals, and the elderly exhibit an increased risk for the development of severe disease after RSV infection. Currently, there is not a safe and effective RSV vaccine available, in part due to our incomplete understanding of how severe immunopathology was induced following RSV infection of children previously immunized with a formalin-inactivated RSV vaccine. Much of our current understanding of RSV vaccine-enhanced disease can be attributed to the establishment of multiple mouse models of RSV vaccination. Studies analyzing the RSV-specific immune response in mice have clearly demonstrated that both CD4 and CD8 memory T cells contribute to RSV-induced immunopathology. In this review we will focus our discussion on data generated from the mouse models of RSV immunization that have advanced our understanding of how virus-specific T cells mediate immunopathology and RSV vaccine-enhanced disease.

Figure 1

Models of the mechanisms of respiratory syncytial virus (RSV) vaccine-enhanced disease. Proposed models for the cells and cytokines required for the development of pulmonary eosinophilia and weight loss in mice immunized with (A) a recombinant vaccinia virus (vacv) expressing the attachment (G) protein of RSV (vacvG), (B) co-immunization with vacvG and a vacv expressing the M2 protein of RSV (vacvM2), and (C) a recombinant vacv expressing the fusion (F) protein of RSV (vacvF).