Madoff L C, Paoletti L C, Tai J Y, Kasper D L
Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Clin Invest. 1994 Jul;94(1):286-92. doi: 10.1172/JCI117319.
Group B streptococcal infection is a major cause of neonatal mortality. Antibody to the capsular polysaccharide protects against invasive neonatal disease, but immunization with capsular polysaccharides fails to elicit protective antibody in many recipients. Conjugation of the polysaccharide to tetanus toxoid has been shown to increase immune response to the polysaccharide. In animal models, C proteins of group B streptococci are also protective determinants. We examined the ability of the beta C protein to serve in the dual role of carrier for the polysaccharide and protective immunogen. Type III polysaccharide was covalently coupled to beta C protein by reductive amination. Immunization of rabbits with the polysaccharide-protein conjugate elicited high titers of antibody to both components, and the serum induced opsonophagocytic killing of type III, Ia/C, and Ib/C strains of group B streptococci. Female mice were immunized with the conjugate vaccine and then bred; 93% of neonatal pups born to these dams vaccinated with conjugate survived type III group B streptococcal challenge and 76% survived type Ia/C challenge, compared with 3% and 8% survival, respectively, in controls (P < 0.001). The beta C protein acted as an effective carrier for the type III polysaccharide while simultaneously induced protective immunity against beta C protein--containing strains of group B streptococci.
B族链球菌感染是新生儿死亡的主要原因。针对荚膜多糖的抗体可预防新生儿侵袭性疾病，但用荚膜多糖进行免疫接种在许多受种者中未能引发保护性抗体。已证明将多糖与破伤风类毒素结合可增强对多糖的免疫反应。在动物模型中，B族链球菌的C蛋白也是保护性决定因素。我们研究了β-C蛋白作为多糖载体和保护性免疫原的双重作用的能力。III型多糖通过还原胺化与β-C蛋白共价偶联。用多糖-蛋白偶联物免疫兔子可引发针对两种成分的高滴度抗体，并且血清可诱导对B族链球菌III型、Ia/C型和Ib/C型菌株的调理吞噬杀伤作用。用偶联疫苗免疫雌性小鼠，然后进行繁殖；这些接种偶联疫苗的母鼠所生的新生幼崽中，93%在受到III型B族链球菌攻击后存活，76%在受到Ia/C型攻击后存活，而对照组的存活率分别为3%和8%（P<0.001）。β-C蛋白作为III型多糖的有效载体，同时诱导针对含β-C蛋白的B族链球菌菌株的保护性免疫。
