Hu Yong, Test Samuel T
Children's Hospital Oakland Research Institute, 5700 Martin Luther King, Jr. Way, Oakland, CA 94609-1673, USA.
Vaccine. 2004 Nov 15;23(1):21-8. doi: 10.1016/j.vaccine.2004.06.039.
We previously have shown that conjugation of C3d to pneumococcal serotype type 14 capsular polysaccharide (PPS14) significantly enhances anti-PPS14 antibody production to a degree similar to that found when the T-dependent protein carrier ovalbumin (OVA) is coupled to PPS14. However, the anti-PPS14 antibody response to PPS14-C3d conjugates is characterized by less switching from IgM to IgG and lower serum concentrations of anti-PPS14 IgG after secondary immunization. To determine if these quantitative differences in anti-PPS14 IgG are accompanied by qualitative differences in the IgG anti-PPS14 antibodies, we performed several functional assays on serum IgG anti-PPS14 antibodies from mice immunized with PPS14-C3d or PPS14-OVA. Compared with antibodies elicited by immunization with PPS14-C3d, IgG anti-PPS14 antibodies produced after immunization with PPS14-OVA were found to have higher avidity and enhanced function as opsonins. Comparisons of avidity for IgG from serum samples obtained after primary and secondary immunization demonstrated a higher degree of avidity maturation after immunization with PPS14-OVA than with PPS14-C3d. These results suggest that PPS14-C3d conjugates are unlikely to be more efficacious than PPS14 conjugate vaccines incorporating T-dependent protein carriers.
我们之前已经表明，将C3d与肺炎球菌14型荚膜多糖（PPS14）偶联可显著增强抗PPS14抗体的产生，其程度与将T细胞依赖性蛋白载体卵清蛋白（OVA）与PPS14偶联时相似。然而，对PPS14-C3d偶联物的抗PPS14抗体反应的特征是，二次免疫后从IgM向IgG的转换较少，且抗PPS14 IgG的血清浓度较低。为了确定抗PPS14 IgG的这些定量差异是否伴随着抗PPS14 IgG抗体的定性差异，我们对用PPS14-C3d或PPS14-OVA免疫的小鼠的血清IgG抗PPS14抗体进行了多项功能测定。与用PPS14-C3d免疫诱导产生的抗体相比，发现用PPS14-OVA免疫后产生的IgG抗PPS14抗体具有更高的亲和力，并且作为调理素的功能增强。对初次和二次免疫后获得的血清样本中的IgG亲和力进行比较，结果表明，与PPS14-C3d免疫相比，PPS14-OVA免疫后亲和力成熟程度更高。这些结果表明，PPS14-C3d偶联物不太可能比包含T细胞依赖性蛋白载体的PPS14结合疫苗更有效。
