Schneerson R, Robbins J B, Chu C, Sutton A, Vann W, Vickers J C, London W T, Curfman B, Hardegree M C, Shiloach J
Infect Immun. 1984 Sep;45(3):582-91. doi: 10.1128/iai.45.3.582-591.1984.
Juvenile and infant rhesus monkeys were injected subcutaneously with saline solutions of Haemophilus influenzae type b (Hib) and pneumococcus type 6A (Pn6A) capsular polysaccharides conjugated to either tetanus toxoid (TT), horseshoe crab hemocyanin, or cholera toxin (CT), and the antibody responses of the monkeys to both bacterial components were measured. All three Hib conjugates were immunogenic and elicited booster responses; their comparative immunogenicity was Hib-CT greater than Hib-TT greater than Hib-horseshoe crab hemocyanin. Hib alone did not elicit antibodies in the juveniles. Juveniles responded earlier and with higher levels of antibodies than did infants. TT, as well as diphtheria-tetanus toxoids-pertussis vaccine adsorbed injected concurrently at a separate site, increased both Hib and TT antibody responses in juveniles (P less than 0.05). Concurrent injection of 5 Lf of fluid TT with a nonimmunogenic 5-micrograms dose in infants elicited levels of Hib antibodies comparable to those elicited by 50 micrograms of Hib-TT. Hib antibodies elicited by the conjugates remained at protective levels in both juveniles and infants 2 months after the last injection, were bactericidal, and conferred passive immunity against bacteremia in infant rats. Passive immunization of juveniles with tetanus immune globulin before each injection of Hib-TT did not suppress Hib antibodies. Hib-TT and Hib-CT elicited increases of Hib antibodies of the immunoglobulin M and G isotypes in the infants. The Pn6A-TT conjugate was considerably less immunogenic than the Hib-TT conjugate; only a few of the juveniles or infants responded with protective levels of Pn6A antibodies. Pn6A antibodies from responders conferred protection in mice against intraperitoneal challenge with Pn6A organisms. TT antibodies were elicited in both juvenile and infant animals after one injection of 50 micrograms of Hib-TT and in the infants injected with 5 micrograms of Hib-TT plus 5 Lf of TT; 5 micrograms of Hib-TT and Pn6A-TT in combination alone did not elicit TT antibodies. Hib-CT elicited CT antibodies in both juveniles and infants.
将b型流感嗜血杆菌(Hib)和6A 型肺炎球菌(Pn6A)的荚膜多糖与破伤风类毒素(TT)、鲎血蓝蛋白或霍乱毒素(CT)偶联后,分别皮下注射给幼年和婴儿恒河猴,并检测这些猴子对两种细菌成分的抗体反应。所有三种Hib偶联物均具有免疫原性并引发加强反应;它们的相对免疫原性为Hib-CT大于Hib-TT大于Hib-鲎血蓝蛋白。单独的Hib在幼年动物中未引发抗体。幼年动物比婴儿更早产生抗体且抗体水平更高。在另一个部位同时注射的TT以及吸附的白喉-破伤风类毒素-百日咳疫苗,增加了幼年动物中Hib和TT的抗体反应(P<0.05)。在婴儿中,将5Lf的液体TT与5微克无免疫原性剂量同时注射,引发的Hib抗体水平与50微克Hib-TT引发的相当。在最后一次注射后2个月,偶联物引发的Hib抗体在幼年和婴儿动物中均保持在保护水平,具有杀菌作用,并赋予幼鼠抗菌血症的被动免疫力。在每次注射Hib-TT之前,用破伤风免疫球蛋白对幼年动物进行被动免疫,并未抑制Hib抗体。Hib-TT和Hib-CT在婴儿中引发了免疫球蛋白M和G同种型的Hib抗体增加。Pn6A-TT偶联物的免疫原性远低于Hib-TT偶联物;只有少数幼年或婴儿动物产生了具有保护水平的Pn6A抗体。来自有反应动物的Pn6A抗体在小鼠中对Pn6A菌株的腹腔攻击具有保护作用。在一次注射50微克Hib-TT后,幼年和婴儿动物均产生了TT抗体,在注射5微克Hib-TT加5Lf TT的婴儿中也产生了TT抗体;单独将5微克Hib-TT和Pn6A-TT联合注射未引发TT抗体。Hib-CT在幼年和婴儿动物中均引发了CT抗体。