IC31, a two-component novel adjuvant mixed with a conjugate vaccine enhances protective immunity against pneumococcal disease in neonatal mice

Abstract

IC31 is a novel adjuvant which combines the immunostimulatory effects of an 11-mer antibacterial peptide (KLKL(5)KLK) and a synthetic oligodeoxynucleotide (ODN1a) which is a Toll-like receptor 9 agonist without containing cytosine phosphate guanine (CpG) motifs. The effects of IC31 on neonatal immune response to vaccination have not been reported. Neonatal mice were immunized once or twice with a Streptococcus pneumoniae serotype 1 polysaccharide conjugate containing Tetanus Toxoid (Pnc1-TT) carrier protein, with or without IC31 or CpG-ODN. IC31 significantly enhanced IgG1, IgG2a and IgG2b antibodies (Ab) to the serotype 1 polysaccharide. One dose of Pnc1-TT and low dose IC31 elicited high Ab levels that protected the neonatal mice completely from bacteraemia and significantly reduced lung infection following i.n. challenge with serotype 1 pneumococcal strain. One-sixth of an adult murine dose of IC31 was sufficient and optimal for induction of protective immunity in neonatal mice. Two doses of Pnc1-TT with or without adjuvants protected the neonatal mice completely, but more rapid Ab response was observed when IC31 was given with the Pnc1-TT. IC31 is a promising new adjuvant for neonatal vaccinations, rapidly enhancing protective humoral responses when combined with Pnc1-TT.