Goldstein J, Hoffman T, Frasch C, Lizzio E F, Beining P R, Hochstein D, Lee Y L, Angus R D, Golding B
Laboratory of Cell Biology, U.S. Food and Drug Administration, Bethesda, Maryland 20892.
Infect Immun. 1992 Apr;60(4):1385-9. doi: 10.1128/iai.60.4.1385-1389.1992.
Brucella abortus may be useful as a component of vaccines. This is because it possesses several unique properties as a carrier that enable it to stimulate human B cells even in the relative absence of T cells. Human immunodeficiency virus type 1 proteins conjugated to B. abortus could induce neutralizing antibodies against human immunodeficiency virus type 1. Recently we showed that the characteristics of lipopolysaccharide (LPS) derived from B. abortus are similar to those of the whole bacterium in that the LPS acts as a T-independent type 1 carrier in mice. In this study we wanted to determine whether LPS derived from B. abortus is associated with the adverse effects seen with other bacterial endotoxins. LPS purified from B. abortus by butanol extraction was shown to have less than 2% (wt/wt) contamination by protein and less than 1% (wt/wt) contamination by nucleic acids and to contain 1% (wt/wt) ketodeoxyoctanic acid. Compared with LPS derived from Escherichia coli, B. abortus LPS was 10,000-fold less potent in eliciting fever in rabbits, 268-fold less potent in killing D-galactosamine-sensitized mice, and 1,400-fold and 400-fold less potent in inducing interleukin-1 beta and tumor necrosis factor alpha production, respectively. These results suggest that B. abortus LPS is much less likely than the LPS from E. coli to evoke endotoxic shock; therefore, it may be feasible to incorporate B. abortus as a component of vaccines.
流产布鲁氏菌可用作疫苗的一个成分。这是因为它作为载体具有若干独特特性,即使在相对缺乏T细胞的情况下也能刺激人类B细胞。与流产布鲁氏菌结合的1型人类免疫缺陷病毒蛋白可诱导针对1型人类免疫缺陷病毒的中和抗体。最近我们发现,流产布鲁氏菌衍生的脂多糖(LPS)的特性与整个细菌的特性相似,因为该LPS在小鼠中作为1型非T细胞依赖性载体起作用。在本研究中,我们想确定流产布鲁氏菌衍生的LPS是否与其他细菌内毒素所见的不良反应有关。通过丁醇萃取从流产布鲁氏菌中纯化的LPS显示,其蛋白质污染低于2%(重量/重量),核酸污染低于1%(重量/重量),并含有1%(重量/重量)的酮脱氧辛酸。与大肠杆菌衍生的LPS相比,流产布鲁氏菌LPS在引发兔发热方面的效力低10000倍,在杀死D-半乳糖胺致敏小鼠方面的效力低268倍,在诱导白细胞介素-1β和肿瘤坏死因子α产生方面的效力分别低1400倍和400倍。这些结果表明,流产布鲁氏菌LPS比大肠杆菌LPS引发内毒素休克的可能性要小得多;因此,将流产布鲁氏菌作为疫苗成分纳入可能是可行的。