Wessels M R, Paoletti L C, Rodewald A K, Michon F, DiFabio J, Jennings H J, Kasper D L
Division of Infectious Diseases, Beth Israel Hospital, Boston, Massachusetts.
Infect Immun. 1993 Nov;61(11):4760-6. doi: 10.1128/iai.61.11.4760-4766.1993.
Antisera elicited by type Ia group B streptococci (GBS) contain antibodies that react with both type Ia and type Ib strains. Previous studies suggested that antibodies elicited by type Ia organisms recognized a carbohydrate antigen or epitope common to Ia and Ib strains. We now report the synthesis and immunogenicity testing of a type Ia polysaccharide-tetanus toxoid (Ia-TT) conjugate vaccine. Ia-TT elicited type Ia polysaccharide-specific immunoglobulin G antibodies in all three of the rabbits inoculated. In competitive enzyme-linked immunosorbent assay, these antibodies reacted with high affinity to type Ia polysaccharide and with lower affinity to the structurally related GBS type Ib polysaccharide. Despite the lower binding affinity of the Ia-TT-induced antibodies for the type Ib polysaccharide, Ia-TT antiserum opsonized not only type Ia GBS but also type Ib GBS for killing by human blood leukocytes. Ia-TT antiserum was also evaluated in a mouse model designed to test the efficacy of maternal antibodies in protecting neonates against GBS infection. Pups born to dams that had received Ia-TT antiserum were protected against lethal challenge with either type Ia or Ib GBS. These studies using a polysaccharide-protein conjugate as an immunogen support the view that the carbohydrate immunodeterminant recognized on Ib strains by Ia antisera is a common epitope contained within the structurally related Ia and Ib capsular polysaccharides. Although antibodies elicited by Ia-TT had protective activity against both Ia and Ib strains, these antibodies reacted with lower affinity to Ib than to Ia polysaccharide.
由Ia型B族链球菌(GBS)引发的抗血清含有能与Ia型和Ib型菌株发生反应的抗体。先前的研究表明,由Ia型微生物引发的抗体识别Ia型和Ib型菌株共有的一种碳水化合物抗原或表位。我们现在报告一种Ia型多糖-破伤风类毒素(Ia-TT)结合疫苗的合成及免疫原性测试。Ia-TT在所有三只接种的兔子中都引发了Ia型多糖特异性免疫球蛋白G抗体。在竞争性酶联免疫吸附测定中,这些抗体与Ia型多糖具有高亲和力反应,而与结构相关的GBS Ib型多糖具有较低亲和力反应。尽管Ia-TT诱导的抗体对Ib型多糖的结合亲和力较低,但Ia-TT抗血清不仅能调理Ia型GBS,还能调理Ib型GBS以便被人血白细胞杀灭。Ia-TT抗血清也在一个旨在测试母体抗体保护新生儿免受GBS感染功效的小鼠模型中进行了评估。接受Ia-TT抗血清的母鼠所生的幼崽能抵抗Ia型或Ib型GBS致死性攻击。这些使用多糖-蛋白质结合物作为免疫原的研究支持了这样一种观点,即Ia型抗血清在Ib型菌株上识别的碳水化合物免疫决定簇是结构相关的Ia型和Ib型荚膜多糖中包含的一个共同表位。尽管由Ia-TT引发的抗体对Ia型和Ib型菌株都有保护活性,但这些抗体与Ib型多糖的反应亲和力低于与Ia型多糖的反应亲和力。