Ambrosino D M, Bolon D, Collard H, Van Etten R, Kanchana M V, Finberg R W
Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Boston, MA 02115.
J Immunol. 1992 Dec 15;149(12):3978-83.
Haemophilus influenzae type b polysaccharide-conjugate vaccines elicit protective antibody responses in young infants. One of these conjugates, polysaccharide linked to outer membrane protein complex (PRP-OMPC), is produced by linking the capsular polysaccharide to an outer membrane protein complex derived from group B Neisseria meningitidis. The outer membrane protein complex contains T cell carrier epitopes that elicit T cell-dependent antibody responses. OMPC also has been shown to increase the antibody response to other proteins administered concurrently that are not covalently linked (i.e., acts as an adjuvant). In this study PRP-OMPC immunized mice demonstrated significant increases in spleen size as well as in splenocyte number as compared to saline controls (p < 0.01, p < 0.001, respectively). No such increase was noted after immunization with another H. influenzae type b-conjugate vaccine, oligosaccharide linked to a variant of diphtheria toxin. By analytic flow cytometry, the mice immunized with PRP-OMPC demonstrated an increase in large splenocytes expressing the Ag Mac-1 (CD11b, CR3). Furthermore, the spleens on histologic examination were characterized by an increase in the red pulp area consisting predominantly of cells of macrophage morphology. By immunohistochemical staining, the cells were identified as macrophages due to expression of Mac-1 and p150,95 (CD11C) Ag. After PRP-OMPC immunization, severe combined immunodeficient mice also demonstrated significant splenomegaly with an increase in macrophages identified by expression of Mac-1 and MHC class II Ag. Thus PRP-OMPC vaccine resulted in T cell-independent splenomegaly with an increase number of macrophages. We propose that this unique property may confer increased immunogenicity to PRP-OMPC through macrophage activation and cytokine release. Furthermore, the effect on macrophages may explain the "adjuvant" capacity of OMPC.
b型流感嗜血杆菌多糖结合疫苗可在幼儿中引发保护性抗体反应。其中一种结合物，即与外膜蛋白复合物（PRP-OMPC）相连的多糖，是通过将荚膜多糖与源自B群脑膜炎奈瑟菌的外膜蛋白复合物连接而产生的。外膜蛋白复合物含有能引发T细胞依赖性抗体反应的T细胞载体表位。OMPC还被证明可增强对同时给予的其他非共价连接蛋白的抗体反应（即起佐剂作用）。在本研究中，与生理盐水对照组相比，用PRP-OMPC免疫的小鼠脾脏大小和脾细胞数量显著增加（分别为p < 0.01，p < 0.001）。用另一种b型流感嗜血杆菌结合疫苗，即与白喉毒素变体相连的寡糖免疫后，未观察到这种增加。通过分析流式细胞术，用PRP-OMPC免疫的小鼠显示表达抗原Mac-1（CD11b，CR3）的大型脾细胞增加。此外，组织学检查发现脾脏红髓面积增加，主要由巨噬细胞形态的细胞组成。通过免疫组化染色，由于表达Mac-1和p150,95（CD11C）抗原，这些细胞被鉴定为巨噬细胞。用PRP-OMPC免疫后，严重联合免疫缺陷小鼠也表现出明显的脾肿大，通过表达Mac-1和MHC II类抗原鉴定出巨噬细胞增加。因此，PRP-OMPC疫苗导致了不依赖T细胞的脾肿大，巨噬细胞数量增加。我们认为，这种独特的特性可能通过巨噬细胞激活和细胞因子释放赋予PRP-OMPC更高的免疫原性。此外，对巨噬细胞的作用可能解释了OMPC的“佐剂”能力。
