The TLR4 agonist, monophosphoryl lipid A, attenuates the cytokine storm associated with respiratory syncytial virus vaccine-enhanced disease

Formalin-inactivated respiratory syncytial virus vaccine (FI-RSV) induces a poorly understood immunopathological response that leads to disease enhancement upon RSV infection of vaccinees. In the cotton rat model, inclusion of monophosphoryl lipid A (MPL) in the FI-RSV formulation was found to mitigate the lung pathology associated with vaccine-enhanced disease. Here we report that the protective effect of MPL on FI-RSV vaccine-enhanced disease is associated with a dramatic reduction in levels of Th1- and Th2-type cytokines and chemokines normally elicited in response to RSV challenge. Our data illustrate the complexity of proinflammatory response elicited by FI-RSV vaccination and RSV infection and the potential importance of MPL in modifying this response.