1. The TLR4 agonist, monophosphoryl lipid A, attenuates the cytokine storm associated with respiratory syncytial virus vaccine-enhanced disease
- Author
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Marina S. Boukhvalova, Gregory A. Prince, Jorge C. G. Blanco, Stefanie N. Vogel, Dolores C. Harrigan, and Layla Soroush
- Subjects
viruses ,medicine.medical_treatment ,Monophosphoryl Lipid A ,Biology ,Virus ,Proinflammatory cytokine ,Adjuvants, Immunologic ,medicine ,Respiratory Syncytial Virus Vaccines ,Animals ,Cotton rat ,Sigmodontinae ,Lung ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,virus diseases ,respiratory system ,medicine.disease ,biology.organism_classification ,Virology ,Respiratory Syncytial Viruses ,Vaccination ,Toll-Like Receptor 4 ,Infectious Diseases ,Cytokine ,Lipid A ,Gene Expression Regulation ,Immunology ,TLR4 ,Molecular Medicine ,Cytokines ,Cytokine storm - Abstract
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.
- Published
- 2005