title: 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.
authors.affiliation: Department of Immunology, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: T A
authors.initials: TA
authors.lastname: Olafsdottir
authors.forename: K
authors.initials: K
authors.lastname: Lingnau
authors.forename: E
authors.initials: E
authors.lastname: Nagy
authors.forename: I
authors.initials: I
authors.lastname: Jonsdottir
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000097:blood; D015169:Colony Count, Microbial; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology; D018709:Statistics, Nonparametric; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C531381:lysyl-leucyl-lysyl-leucyl-leucyl-leucyl-leucyl-leucyl-lysyl-leucyl-lysine