Stark Felicity C, McCluskie Michael J, Krishnan Lakshmi
Human Health Therapeutics, National Research Council of Canada, 1200 Montreal Rd., Ottawa, ON K1A 0R6, Canada.
Vaccines (Basel). 2016 Nov 17;4(4):44. doi: 10.3390/vaccines4040044.
Homologous prime-boost vaccinations with live vectors typically fail to induce repeated strong CD8⁺ T cell responses due to the induction of anti-vector immunity, highlighting the need for alternative delivery vehicles. The unique ether lipids of archaea may be constituted into liposomes, archaeosomes, which do not induce anti-carrier responses, making them an ideal candidate for use in repeat vaccination systems. Herein, we evaluated in mice the maximum threshold of antigen-specific CD8⁺ T cell responses that may be induced by multiple homologous immunizations with ovalbumin (OVA) entrapped in archaeosomes derived from the ether glycerolipids of the archaeon (MS-OVA). Up to three immunizations with MS-OVA administered in optimized intervals (to allow for sufficient resting of the primed cells prior to boosting), induced a potent anti-OVA CD8⁺ T cell response of up to 45% of all circulating CD8⁺ T cells. Additional MS-OVA injections did not add any further benefit in increasing the memory of CD8⁺ T cell frequency. In contrast, OVA expressed by (LM-OVA), an intracellular bacterial vector failed to evoke a boosting effect after the second injection, resulting in significantly reduced antigen-specific CD8⁺ T cell frequencies. Furthermore, repeated vaccination with MS-OVA skewed the response increasingly towards an effector memory (CD62) phenotype. Vaccinated animals were challenged with B16-OVA at late time points after vaccination (+7 months) and were afforded protection compared to control. Therefore, archaeosomes constituted a robust particulate delivery system to unravel the kinetics of CD8⁺ T cell response induction and memory maintenance and constitute an efficient vaccination regimen optimized for tumor protection.
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