Schneerson R, Robbins J B, Parke J C, Bell C, Schlesselman J J, Sutton A, Wang Z, Schiffman G, Karpas A, Shiloach J
Infect Immun. 1986 May;52(2):519-28. doi: 10.1128/iai.52.2.519-528.1986.
Covalent binding to immunogenic proteins increases the immunogenicity of the capsular polysaccharides of Haemophilus influenzae type b (Hib) and pneumococcus type 6A (Pn6A). Conjugates composed of Hib, Pn6A, or the cross-reacting Escherichia coli K100 covalently bound to tetanus toxoid (TT) were injected into young adult volunteers. Local reactions were common and were probably due to Arthus reactivity mediated by the preexisting antibodies reacting with the TT component of the conjugates. Fever occurred in about 10% of the volunteers after the first injection; no volunteers had fever after the second injection. Similar levels of Hib or Pn6A antibodies were elicited by either 50- or 100-micrograms doses or by concurrent injection of two different conjugates (Hib-TT and Pn6A-TT or Hib-TT and K100-TT). The Hib-TT elicited about a 180-fold increase in Hib antibodies, and the Pn6A-TT conjugate elicited about an 8-fold increase in Pn6A antibodies after one injection. Booster reactions were not elicited in adults; similar levels of antibodies in the five experimental groups suggested that the responses elicited by the conjugates were maximal. A one-way cross-reaction was noted as Pn6A conjugates elicited rises of Hib antibodies in 13 of 20 volunteers; only 4 of 59 volunteers immunized with Hib-TT had increases in Pn6A antibodies. The preimmunization Hib antibodies were composed of immunoglobulin M (IgM), IgA, and IgG. The postimmunization sera showed an increase in all three isotypes; the elevation of the IgG was the highest of the three isotypes. Conjugate-induced antibodies to both the polysaccharide and TT exerted biological activities that have been correlated with immunity. Adsorption of the Hib-TT onto aluminium hydroxide resulted in higher levels and an earlier Hib antibody response in infant rhesus. These results encourage the evaluation of Hib and Pn6A conjugates in human children and infants.
与免疫原性蛋白质的共价结合增加了b型流感嗜血杆菌（Hib）和6A 型肺炎球菌（Pn6A）荚膜多糖的免疫原性。将由Hib、Pn6A或与破伤风类毒素（TT）共价结合的交叉反应性大肠杆菌K100组成的结合物注射到年轻成年志愿者体内。局部反应很常见，可能是由于预先存在的抗体与结合物的TT成分发生反应介导的阿瑟反应。首次注射后约10%的志愿者出现发热；第二次注射后没有志愿者发热。50微克或100微克剂量的结合物或同时注射两种不同的结合物（Hib-TT和Pn6A-TT或Hib-TT和K100-TT）诱导产生的Hib或Pn6A抗体水平相似。一次注射后，Hib-TT诱导Hib抗体增加约180倍，Pn6A-TT结合物诱导Pn6A抗体增加约8倍。在成年人中未引发加强反应；五个实验组中相似的抗体水平表明结合物引发的反应已达到最大值。观察到单向交叉反应，因为Pn6A结合物在20名志愿者中的13名中引发了Hib抗体升高；用Hib-TT免疫的59名志愿者中只有4名Pn6A抗体增加。免疫前的Hib抗体由免疫球蛋白M（IgM）、IgA和IgG组成。免疫后的血清显示所有三种同种型均增加；IgG的升高在三种同种型中最高。结合物诱导的针对多糖和TT的抗体发挥了与免疫相关的生物学活性。将Hib-TT吸附到氢氧化铝上可使恒河猴婴儿体内的Hib抗体水平更高且反应更早。这些结果鼓励对人类儿童和婴儿中的Hib和Pn6A结合物进行评估。
