Betts M, Beining P, Brunswick M, Inman J, Angus R D, Hoffman T, Golding B
Laboratory of Cell Biology, U.S. Food and Drug Administration, Bethesda, Maryland.
Infect Immun. 1993 May;61(5):1722-9. doi: 10.1128/iai.61.5.1722-1729.1993.
In order to determine the carrier nature of lipopolysaccharide from Brucella abortus (LPS-BA) in evoking humoral responses, normal and immunodeficient mice were immunized with trinitrophenyl (TNP)-conjugated LPS-BA (TNP-LPS-BA) and the responses were compared with those to known T-dependent and T-independent antigens. TNP-LPS-BA, like T-independent type 1 (TI-1) antigens such as TNP-BA and TNP-LPS from Escherichia coli (TNP-LPS-EC), generated anti-TNP responses in BALB/c, athymic BALB/c nu/nu, and CBA/N mice. In contrast, N-2,4-dinitrophenyl-beta-alanylglycylglycyl-substituted keyhole limpet hemocyanin, a typical T-dependent antigen, was not immunogenic in athymic mice, and TNP-Ficoll (T-independent type 2) was ineffective in eliciting humoral responses in CBA/N mice. These results indicate that LPS from B. abortus acts as a TI-1 carrier in generating antibody responses. In C3H/HeJ mice, TNP-LPS-BA generated higher-titer immunoglobulin G1 (IgG1), IgG2a, and IgG2b anti-TNP antibodies than TNP-LPS-EC. Compared with those from BALB/c mice, pure resting B cells isolated from C3H/HeJ mice exhibited a 30-fold lower proliferative response to LPS-EC, whereas the LPS-BA response was reduced to a lesser extent (5-fold). This suggests that the disparity observed in antibody titers was due to different abilities of LPS from B. abortus and E. coli to stimulate C3H/HeJ B cells. The ability of LPS from B. abortus to act as a carrier in generating humoral immune responses indicates that LPS-BA can be substituted for whole B. abortus organisms in vaccine development.
为了确定流产布鲁氏菌脂多糖(LPS-BA)在引发体液免疫反应中的载体性质,用三硝基苯基(TNP)偶联的LPS-BA(TNP-LPS-BA)免疫正常和免疫缺陷小鼠,并将反应与已知的T细胞依赖性和T细胞非依赖性抗原的反应进行比较。TNP-LPS-BA与T细胞非依赖性1型(TI-1)抗原如TNP-BA和来自大肠杆菌的TNP-LPS(TNP-LPS-EC)一样,在BALB/c、无胸腺BALB/c nu/nu和CBA/N小鼠中产生抗TNP反应。相比之下,典型的T细胞依赖性抗原N-2,4-二硝基苯基-β-丙氨酰甘氨酰甘氨酰取代的钥孔戚血蓝蛋白在无胸腺小鼠中无免疫原性,而TNP-菲可(T细胞非依赖性2型)在CBA/N小鼠中引发体液免疫反应无效。这些结果表明,流产布鲁氏菌的LPS在产生抗体反应中起TI-1载体的作用。在C3H/HeJ小鼠中,TNP-LPS-BA产生的抗TNP抗体的免疫球蛋白G1(IgG1)、IgG2a和IgG2b滴度高于TNP-LPS-EC。与来自BALB/c小鼠的相比,从C3H/HeJ小鼠分离的纯静息B细胞对LPS-EC的增殖反应低30倍,而对LPS-BA的反应降低程度较小(5倍)。这表明观察到的抗体滴度差异是由于流产布鲁氏菌和大肠杆菌的LPS刺激C3H/HeJ B细胞的能力不同。流产布鲁氏菌的LPS作为产生体液免疫反应载体的能力表明,LPS-BA可在疫苗开发中替代完整的流产布鲁氏菌。