首页> 美国卫生研究院文献>Infection and Immunity >CpG Oligodeoxynucleotides Act as Adjuvants for Pneumococcal Polysaccharide-Protein Conjugate Vaccines and Enhance Antipolysaccharide Immunoglobulin G2a (IgG2a) and IgG3 Antibodies
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CpG Oligodeoxynucleotides Act as Adjuvants for Pneumococcal Polysaccharide-Protein Conjugate Vaccines and Enhance Antipolysaccharide Immunoglobulin G2a (IgG2a) and IgG3 Antibodies

机译:CpG寡脱氧核苷酸可作为肺炎球菌多糖-蛋白质结合疫苗的佐剂并增强抗多糖免疫球蛋白G2a(IgG2a)和IgG3抗体

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摘要

Pneumococcal polysaccharide-protein conjugate vaccines elicit antipolysaccharide antibodies, but multiple doses are required to achieve protective antibody levels in children. In addition, the immunogenicity of experimental multivalent pneumococcal conjugate vaccines varies with different polysaccharide 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-cell and T-dependent antibody responses to protein antigens, but it has been unclear whether CpG ODN can enhance polysaccharide-specific antibody responses. The present studies demonstrate significant adjuvant activity of CpG ODN for antibody responses against Streptococcus pneumoniae polysaccharide types 19F and 6B induced by conjugates of 19F and 6B with the protein carrier 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 antibodies by enzyme-linked immunosorbent assay. The polysaccharide-specific antibody response to 19F-CRM197 alone was predominantly of the immunoglobulin G1 (IgG1) 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 response to 6B-CRM197 alone consisted only of IgM, but addition of CpG ODN induced 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 control non-CpG ODN. Thus, CpG ODN significantly enhance antipolysaccharide IgG responses (especially IgG2a and IgG3) induced by these glycoconjugate vaccines.
机译:肺炎球菌多糖-蛋白结合疫苗可产生抗多糖抗体,但需要多次剂量才能达到儿童的保护性抗体水平。另外,实验性多价肺炎球菌结合疫苗的免疫原性随不同的多糖血清型而变化。改善这些疫苗的一种策略是掺入佐剂以增强其免疫原性。含有未甲基化CpG基序(CpG ODN)的合成寡聚脱氧核苷酸是促进T细胞和T依赖性抗体对蛋白质抗原反应的佐剂,但尚不清楚CpG ODN是否可以增强多糖特异性抗体反应。本研究表明,CpG ODN对于由19F和6B与蛋白质载体CRM197缀合物诱导的抗19F和6B型肺炎链球菌多糖抗体反应具有显着的佐剂活性。向BALB / c ByJ小鼠注射带有或不带有CpG ODN的19F-CRM197或6B-CRM197,并通过酶联免疫吸附试验检测血清的抗19F或抗6B抗体。单独对19F-CRM197的多糖特异性抗体反应主要是免疫球蛋白G1(IgG1)和IgM同种型,但是添加CpG ODN显着增加了总抗19F抗体(23倍),抗19F IgG2a的几何平均滴度。 (26倍)和抗19F IgG3(> 246倍)。单独对6B-CRM197的多糖特异性抗体反应仅由IgM组成,但是添加CpG ODN会诱导高滴度的抗6B IgG1(增加78倍),抗6B IgG2a(增加54倍)和抗6B IgG3(> 3,162倍增加)。 CpG ODN也增加了抗CRM197 IgG2a和IgG3。对照非CpG ODN未观察到佐剂作用。因此,CpG ODN显着增强了这些糖缀合物疫苗诱导的抗多糖IgG反应(尤其是IgG2a和IgG3)。

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