IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

“…The number of vaccine-bearing LN DC remained stable up to the last time point assessed (7 days), in accordance with the longlasting depot observed at the site of immunization with IC31 [16,20]. Considering steady-state and immunization-induced DC turnover [21][22][23] in LN, this persistence of vaccine-bearing DC in LN is consistent with continuous replenishment from the site of immunization.…”

“…IC31 has a main immunostimulatory function as it is ineffective in TLR9-deficient and MyD88 -/-mice [16]. Remarkably, this activation is restricted in vivo on <0.3% of CD11c + LN DC.…”

“…OVA-FITC was purchased from Invitrogen. IC31, consisting of KLK (NH 2 -KLKLLLLLKLK-COOH) and ODN1a (phosphodiester backbone ODN, 5 0 -ICICICICICICICICICICICICIC-3 0 ), including TAMRA-coupled KLK and Cy5-coupled ODN1a, was produced as described [16]. LPS (5 lg/mouse; Sigma) and CpG 1826 and control CpG 1982 (5 nmol/mouse [28]) were used as controls.…”

“…Towards this aim, mice were immunized with a fusion protein of two major tuberculosis antigens (Ag85B and 6-kDa early secretory antigenic target (ESAT-6)) capable of inducing protection in murine tuberculosis challenge models [14,15] when formulated with the potent novel IC31 (IC31 J registered CTM and US trademark, herein named as IC31) adjuvant containing a KLK peptide and a TLR9-triggering non-CpG oligodeoxynucleotide (ODN)1a [16]. This candidate vaccine was shown to induce potent IFN-c responses in a clinical trial (www.intercell.com/ShowArticle.…”

IC31®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice

“…ODN1a consists of dimeric repeats of deoxy-Inosine ⁄ deoxy-Cytosine linked by an unmodified phosphodiester backbone and was designed to bypass possible systemic side effects of CpG-ODN, stimulating high levels of IL-6 and tumour necrosis factor (TNF)-a. ODN1a on its own has no immunostimulatory effects which is probably due to its short half-life based on its phophodiester backbone. IC31 Ò has been shown to enhance antigen-specific cytotoxic T lymphocyte activity [20], induce mixed Th1-and Th2-associated humoral responses [20,21] and provide significant protection against tuberculosis (TB), when co-administrated with a TB vaccine candidate [21]. IC31 Ò had no systemic toxic effects in rats and did not induce systemic pro-inflammatory cytokines IL-6 and TNF-a [20].…”