Rapid Clonal Expansion and Prolonged Maintenance of Memory CD8 super(+) T Cells of the Effector (CD44 super(high)CD62L super(low)) and Central (CD44 super(high)CD62L super(high)) Phenotype by an Archaeosome Adjuvant Independent of TLR2

• Published in: Journal of Immunology Vol. 178; no. 4; pp. 2396 - 2406
• Main Authors: Krishnan, Lakshmi, Gurnani, Komal, Dicaire, Chantal J, van Faassen, Henk, Zafer, Ahmed, Kirschning, Carsten J, Sad, Subash, Sprott, GDennis
• Format: Journal Article
• Language: English
• Published: 01.02.2007
• Subjects: Listeria
• ISSN: 0022-1767; 1365-2567

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 super(+) T cells to Ag entrapped in archaeal glycerolipid vesicles (archaeosomes). In this study, we evaluated the priming, phenotype, and functionality of the CD8 super(+) 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 super(b)OVA sub(257-264)-specific CD8 super(+) T cells declined by 14-21 days, and <1% of primarily central phenotype (CD44 super(high)CD62L super(high)) cells persisted. A booster injection of MS-OVA at 3-11 wk promoted massive clonal expansion and a peak effector response of similar to 20% splenic/blood OVA sub(257-264)-specific CD8 super(+) T cells. Furthermore, contraction was protracted and the memory pool (IL-7R alpha super(high)) of similar to 5% included effector (CD44 super(high)CD62L super(low)) and central (CD44 super(high)CD62L super(high)) phenotype cells. Recall response was observed even at >300 days. CFSE-labeled naive OT-1 (OVA sub(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, similar to 25% cycling of Ag-specific cells was seen for >50 days, suggesting an Ag depot. In vivo, CD8 super(+) 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 super(+) 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 super(+) T cell memory.