CpG oligodeoxynucleotides act as adjuvants for pneumococcal polysaccharide-protein conjugate vaccines and enhance antipolysaccharide immunoglobulin G2a (IgG2a) and IgG3 antibodies

Pneumococcal polysaccharide-protein conjugate vaccines elicit antipolysacch aride antibodies, but multiple doses are required to achieve protective ant ibody levels in children. In addition, the immunogenicity of experimental m ultivalent pneumococcal conjugate vaccines varies with different polysaccha ride serotypes, One strategy to improve these vaccines is to incorporate an adjuvant to enhance their immunogenicity. Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are adjuvants that promote T-c ell and T-dependent antibody responses to protein antigens, but it has been unclear whether CpG ODN can enhance polysaccharide-specific antibody respo nses, The present studies demonstrate significant adjuvant activity of CpG ODN for antibody responses against Streptococcus pneumoniae poly-saccharide types 19F and 6B induced by conjugates of 19F and 6B with the protein carr ier CRM197. BALB/c ByJ mice were injected with 19F-CRM197 or 6B-CRM197 with or without CpG ODN, and sera were tested for anti-19F or anti-6B antibodie s by enzyme-linked immunosorbent assay. The polysaccharide-specific antibod y response to 6B-CRM197 alone was predominantly of the immunoglobulin GI (I gG1) and IgM isotypes, but addition of CpG ODN markedly increased geometric mean titers of total anti-19F antibody (23-fold), anti-19F IgG2a (26-fold) , and anti-19F IgG3 (>246-fold). The polysaccharide-specific antibody respo nse to 6B-CRM197 alone consisted only of IgM, but addition of CpG ODN induc ed high titers of anti-6B IgG1 (>78-fold increase), anti-6B IgG2a (>54-fold increase), and anti-6B IgG3 (>3,162-fold increase). CPG ODN also increased anti-CRM197 IgG2a and IgG3. Adjuvant effects were not observed with contro l non-CpG ODN. Thus, CpG ODN significantly enhance antipolysaccharide IgG r esponses (especially IgG2a and IgG3) induced by these glycoconjugate vaccin es.