Co-localization of a CD1d-binding glycolipid with an adenovirus-based malaria vaccine for a potent adjuvant effect.
A CD1d-binding, invariant (i) natural killer T (NKT)-cell stimulatory glycolipid, α-Galactosylceramide (αGalCer), has been shown to act as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying a higher binding affinity for CD1d molecule and more potent adjuvant activity than αGalCer. 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.
['Li|Xiangming|X|', 'Huang|Jing|J|', 'Kawamura|Akira|A|', 'Funakoshi|Ryota|R|', 'Porcelli|Steven A|SA|', 'Tsuji|Moriya|M|']
D000256:Adenoviridae D000276:Adjuvants, Immunologic D000818:Animals D055610:Antigens, CD1d D000953:Antigens, Protozoan D018414:CD8-Positive T-Lymphocytes D003713:Dendritic Cells D005699:Galactosylceramides D000071497:Immunogenicity, Vaccine D007273:Injections, Intramuscular D007371:Interferon-gamma D007694:Killer Cells, Natural D008213:Lymphocyte Activation D008288:Malaria D017780:Malaria Vaccines D051379:Mice D055611:Natural Killer T-Cells D010967:Plasmodium yoelii D014614:Vaccines, Synthetic
Co-localization Malaria vaccine CD1d Adenovirus Lymph node Dendritic cells CD8+ T cells Protection Glycolipid adjuvant Intramuscular injection