title: Rapid clonal expansion and prolonged maintenance of memory CD8+ T cells of the effector (CD44highCD62Llow) and central (CD44highCD62Lhigh) phenotype by an archaeosome adjuvant independent of TLR2.
abstract: Vaccines capable of eliciting long-term T cell immunity are required for combating many diseases. Live vectors can be unsafe whereas subunit vaccines often lack potency. We previously reported induction of CD8(+) T cells to Ag entrapped in archaeal glycerolipid vesicles (archaeosomes). In this study, we evaluated the priming, phenotype, and functionality of the CD8(+) T cells induced after immunization of mice with OVA-Methanobrevibacter smithii archaeosomes (MS-OVA). A single injection of MS-OVA evoked a profound primary response but the numbers of H-2K(b)OVA(257-264)-specific CD8(+) T cells declined by 14-21 days, and <1% of primarily central phenotype (CD44(high)CD62L(high)) cells persisted. A booster injection of MS-OVA at 3-11 wk promoted massive clonal expansion and a peak effector response of approximately 20% splenic/blood OVA(257-264)-specific CD8(+) T cells. Furthermore, contraction was protracted and the memory pool (IL-7Ralpha(high)) of approximately 5% included effector (CD44(high)CD62L(low)) and central (CD44(high)CD62L(high)) phenotype cells. Recall response was observed even at >300 days. CFSE-labeled naive OT-1 (OVA(257-264) TCR transgenic) cells transferred into MS-OVA-immunized recipients cycled profoundly (>90%) within the first week of immunization indicating potent Ag presentation. Moreover, approximately 25% cycling of Ag-specific cells was seen for >50 days, suggesting an Ag depot. In vivo, CD8(+) T cells evoked by MS-OVA killed >80% of specific targets, even at day 180. MS-OVA induced responses similar in magnitude to Listeria monocytogenes-OVA, a potent live vector. Furthermore, protective CD8(+) T cells were induced in TLR2-deficient mice, suggesting nonengagement of TLR2 by archaeal lipids. Thus, an archaeosome adjuvant vaccine represents an alternative to live vectors for inducing CD8(+) T cell memory.
authors.affiliation: National Research Council-Institute for Biological Sciences, Ottawa, Ontario, Canada. Lakshmi.Krishnan@nrc-cnrc.gc.ca
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Krishnan
authors.forename: Komal
authors.initials: K
authors.lastname: Gurnani
authors.forename: Chantal J
authors.initials: CJ
authors.lastname: Dicaire
authors.forename: Henk
authors.initials: H
authors.lastname: van Faassen
authors.forename: Ahmed
authors.initials: A
authors.lastname: Zafer
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Subash
authors.initials: S
authors.lastname: Sad
authors.forename: G Dennis
authors.initials: GD
authors.lastname: Sprott
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology*; D007156:Immunologic Memory; D019041:L-Selectin / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D041581:Methanobrevibacter / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000276:immunology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D020395:Receptors, Interleukin-7; D051195:Toll-Like Receptor 2; D019041:L-Selectin; D010047:Ovalbumin