期刊
VACCINE
卷 30, 期 35, 页码 5206-5214出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2012.06.011
关键词
RSV fusion protein; Protection; Polyphosphazene microparticles
资金
- Krembil Foundation
- Canadian Institutes of Health Research (CIHR)
- Bill and Melinda Gates Foundation
Although respiratory syncytial virus (RSV) is the leading cause of serious respiratory tract disease in children, to date no RSV vaccine is available. To produce an effective subunit vaccine, a truncated secreted version of the F protein (Delta F) was expressed in mammalian cells, purified and shown to form trimers. The Delta F protein was then formulated with a CpG oligodeoxynucleotide (ODN) and an innate defense regulator (IDR) peptide in polyphosphazene microparticles (Delta F-MP). Mice immunized either intramuscularly (IM) or intranasally (IN) with Delta F-MP developed significantly higher levels of virus-neutralizing antibodies in the sera and lungs, as well as higher numbers of IFN-gamma secreting cells than mice immunized with the Delta F protein alone. In contrast, the IM delivered Delta F induced high production of IL-5 while the IN delivered Delta F did not elicit a measurable immune response. After RSV challenge, essentially no virus and no evidence of immunopathology were detected in mice immunized with Delta F-MP regardless of the route of delivery. While the mice immunized IM with Delta F alone also showed reduced virus replication, they developed enhanced levels of pulmonary IgE, IL-4, IL-5, IL-13 and eotaxin, as well as eosinophilia after challenge. The level of protection induced by the Delta F-MP formulation was equivalent after IM and IN delivery. The efficacy and safety of the Delta F-MP formulation was confirmed in cotton rats, which also developed enhanced immune responses and were fully protected from RSV challenge after vaccination with Delta F-MP. In conclusion, formulation of recombinant Delta F with CpG ODN and IDR peptide in polyphosphazene microparticles should be considered for further evaluation as a safe and effective vaccine against RSV. (C) 2012 Elsevier Ltd. All rights reserved.
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