title: In vivo activity of cationic immune stimulating complexes (PLUSCOMs).
abstract: A particulate vaccine delivery system consisting of cationic ISCOM derivatives (PLUSCOMs) was compared to classic anionic ISCOMs with regard to antigen attachment and ability to elicit in vivo T cell responses against a model protein antigen (ovalbumin [OVA]). ISCOMs did not incorporate hydrophilic OVA whilst OVA readily adsorbed onto PLUSCOMs with increasing adsorption at higher protein concentrations. The zeta-potential of PLUSCOMs significantly decreased with increasing protein load, suggesting neutralization of the cationic charge upon absorption of the anionic OVA. Antigen-specific CD8 T cell responses were demonstrated in mice vaccinated with either PLUSCOMs or ISCOMs. Ex vivo restimulation of harvested T cells demonstrated that cells isolated from PLUSCOM and ISCOM vaccinated mice responded to the secondary OVA challenge more efficiently than mice vaccinated with OVA in solution. Restimulated cells from the mice vaccinated with particulate vaccines produced significantly more INF-gamma. Therefore PLUSCOMs are as effective as classic ISCOMs in inducing antigen-specific CD8 T cell responses and have advantages with regard to the incorporation of purified anionic antigens.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Warren T
authors.initials: WT
authors.lastname: McBurney
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Lendemans
authors.forename: Julia
authors.initials: J
authors.lastname: Myschik
authors.forename: Tania
authors.initials: T
authors.lastname: Hennessy
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Sarah
authors.initials: S
authors.lastname: Hook
mesh_terms: D000327:Adsorption; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016882:ISCOMs / Q000737:chemistry* / Q000276:immunology* / Q000648:ultrastructure; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D011485:Protein Binding; D012717:Sesquiterpenes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016882:ISCOMs; D012717:Sesquiterpenes; C002781:ovalicin; D007371:Interferon-gamma