CpG oligodeoxynucleotides act as adjuvants for pneumococcal polysaccharide-protein conjugate vaccines and enhance antipolysaccharide immunoglobulin G2a (IgG2a) and IgG3 antibodies
CpG oligodeoxynucleotides act as adjuvants for pneumococcal polysaccharide-protein conjugate vaccines and enhance antipolysaccharide immunoglobulin G2a (IgG2a) and IgG3 antibodies
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DOI：
10.1128/iai.68.3.1450-1456.2000
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发表时间：
2000-03-01
影响因子：
3.1
通讯作者：
Harding, CV
中科院分区：
文献类型：
--
作者：
Chu, RS;McCool, T;Harding, CV
肺炎球菌多糖-蛋白结合物疫苗可引发抗多糖抗体，但需要多次接种才能使儿童达到保护性抗体水平。此外，实验性多价肺炎球菌缀合物疫苗的免疫原性随不同多糖血清型而变化，改进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基序的合成寡脱氧核苷酸（CpG ODN）是促进T细胞和T依赖性抗体对蛋白质抗原的应答的佐剂，但CpG ODN是否能增强多糖特异性抗体应答一直不清楚，目前的研究表明，CpG ODN对肺炎链球菌多聚体的抗体应答具有显著的佐剂活性。通过19 F和6 B与蛋白质载体CRM 197的缀合物诱导的糖型19 F和6 B。BALB/c ByJ小鼠分别注射含或不含CpG ODN的19 F-CRM 197或6 B-CRM 197，通过酶联免疫吸附试验检测血清中抗19 F或抗6 B抗体。单独对6 B-CRM 197的多糖特异性抗体应答主要是免疫球蛋白GI（IgG 1）和IgM同种型，但添加CpG ODN显著增加总抗19 F抗体（23倍）、抗19 F IgG 2a（26倍）和抗19 F IgG 3（>246倍）的几何平均滴度。对单独的6 B-CRM 197的多糖特异性抗体应答仅由IgM组成，但添加CpG ODN诱导高滴度的抗6 B IgG 1（>78倍增加）、抗6 B IgG 2a（>54倍增加）和抗6 B IgG 3（> 3，162倍增加）。CPG ODN还增加抗CRM 197 IgG 2a和IgG 3。用对照非CpG ODN未观察到佐剂效应。因此，CpG ODN显著增强由这些糖缀合物疫苗诱导的抗多糖IgG应答（尤其是IgG 2a和IgG 3）。
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 poly-saccharide 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 6B-CRM197 alone was predominantly of the immunoglobulin GI (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.