Co-localization of a CD1d-binding glycolipid with an adenovirus-based malaria vaccine for a potent adjuvant effect.

ABSTRACT: A CD1d-binding, invariant (i) natural killer T (NKT)-cell stimulatory glycolipid, ?-Galactosylceramide (?GalCer), has been shown to act as an adjuvant. We previously identified a fluorinated phenyl ring-modified ?GalCer analog, 7DW8-5, displaying a higher binding affinity for CD1d molecule and more potent adjuvant activity than ?GalCer. In the present study, 7DW8-5 co-administered intramuscularly (i.m.) with a recombinant adenovirus expressing a Plasmodium yoelii circumsporozoite protein (PyCSP), AdPyCS, has led to a co-localization of 7DW8-5 and a PyCSP in draining lymph nodes (dLNs), particularly in dendritic cells (DCs). This occurrence initiates a cascade of events, such as the recruitment of DCs to dLNs and their activation and maturation, and the enhancement of the ability of DCs to prime CD8+ T cells induced by AdPyCS and ultimately leading to a potent adjuvant effect and protection against malaria.

SUBMITTER: Li X 

PROVIDER: S-EPMC5489412 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature