Pillars article: the CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. 1988.

摘要

West Nile virus (WNV) can cause severe acute fever and encephalitis in humans, but no Food and Drug Administration-approved vaccines against WNV are available. Demento et al. (p. 2989) tested a novel approach to vaccination against WNV using biodegradable nanopartides containing rWNV envelope (WNVE) protein. In vitro stimulation of bone marrow-derived dendritic cells with WNVE-loaded nanopartides tethered witli immunostimulatory TLR9-speciflc CpG oligodeoxynucleotides (ODNs) promoted activation and induced secretion of IL-6 and IL-12 compared with cells stimulated with WNVE-loaded particles lacking CpG ODNs or rWNVE adsorbed onto aluminum hydroxide (alum) adjuvant. High titers of IgGl were induced by the alum formulation, indicative of a Th2-biased response. In contrast, CpG ODN-modified rWNVE-loaded particles induced a Thl-biased response, indicated by high levels of IgG2a and IgG2b. Splenocytes from mice immunized with CpG ODN-modified rWNVE-loaded particles released greater amounts of IL-2 and IFN-7 upon ex vivo stimulation compared with splenocytes from mice immunized witli unmodified WNVE particles or alum-adsorbed rWNVE. Moreover, immunization with CpG ODN-modified rWNV-loaded particles induced a greater frequency of circulating effector T cells and provided superior protection against WNV encephalitis in infected mice compared witli other vaccine formulations. These results provide insight into a potentially effective approach for vaccination against WNV.