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

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.

• Authors: Marina S Boukhvalova, Gregory A Prince, Layla Soroush, Dolores C Harrigan, Stefanie N Vogel, Jorge C G Blanco
• Journal: Vaccine (Vaccine) Vol. 24 Issue 23 Pg. 5027-35 (Jun 05 2006) ISSN: 0264-410X [Print] Netherlands
• PMID: 16675071 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Cytokines
• Lipid A
• Respiratory Syncytial Virus Vaccines
• Toll-Like Receptor 4
• monophosphoryl lipid A

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Cytokines (antagonists & inhibitors, immunology, metabolism)
• Gene Expression Regulation
• Lipid A (analogs & derivatives, pharmacology)
• Lung (metabolism, pathology)
• Respiratory Syncytial Virus Vaccines (adverse effects, immunology)
• Respiratory Syncytial Viruses (immunology)
• Sigmodontinae (immunology)
• Toll-Like Receptor 4 (agonists)