A virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A provides protection against viral challenge without priming for enhanced disease in cotton rats

作者：Kamphuis Tobias; Stegmann Toon; Meijerhof Tjarko; Wilschut Jan; de Haan Aalzen^*

来源：Influenza and Other Respiratory Viruses, 2013, 7(6): 1227-1236.

DOI：10.1111/irv.12112

• Adjuvant
• cotton rat
• enhanced respiratory disease
• monophosphoryl lipid A
• respiratory syncytial virus
• vaccine
• virosomes

Background Non-replicating respiratory syncytial virus (RSV) vaccine candidates could potentially prime for enhanced respiratory disease (ERD) due to a T-cell-mediated immunopathology, following RSV infection. Vaccines with built-in immune response modifiers, such as Toll-like receptor (TLR) ligands, may avoid such aberrant imprinting of the immune system. %26lt;br%26gt;Methods We developed reconstituted RSV envelopes (virosomes) with incorporated TLR4 ligand, monophosphoryl lipid A (RSV-MPLA virosomes). Immune responses and lung pathology after vaccination and challenge were investigated in ERD-prone cotton rats and compared with responses induced by live virus and formaldehyde-inactivated vaccine (FI-RSV), a known cause of ERD upon RSV challenge. %26lt;br%26gt;Results Vaccination with RSV-MPLA virosomes induced higher levels of virus-neutralizing antibodies than FI-RSV or live virus infection and provided protection against infection. FI-RSV, but not RSV-MPLA virosomes, primed for increases in expression of Th2 cytokines IL-4, IL-5, IL-13, and Th1 cytokine IL-1b, 6 hour-5 days after infection. By contrast, RSV-MPLA virosomes induced IFN-gamma transcripts to similar levels as induced by live virus. Animals vaccinated with FI-RSV, but not RSV-MPLA virosomes showed alveolitis, with prominent neutrophil influx and peribronchiolar and perivascular infiltrates. %26lt;br%26gt;Conclusion These results show that RSV-MPLA virosomes represent a safe and immunogenic vaccine candidate that warrants evaluation in a clinical setting.

• 出版日期2013-11