Fattom A, Lue C, Szu S C, Mestecky J, Schiffman G, Bryla D, Vann W F, Watson D, Kimzey L M, Robbins J B
Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Infect Immun. 1990 Jul;58(7):2309-12. doi: 10.1128/iai.58.7.2309-2312.1990.
Conjugates of an uronic acid-containing capsular polysaccharide (CP), pneumococcous type 12F (Pn12F) bound to diphtheria toxoid (DT), were studied for safety and immunogenicity in adult volunteers. In mice, these conjugates, prepared with the same lot of DT and Pn12F-40234-006, a homogenous CP of high molecular weight, or Pn12-812408, a polydisperse CP with lower-molecular-weight material, were more immunogenic than the Pn12F alone and had T-cell dependent properties (A. Fattom, W. F. Vann, S.C. Szu, A. Sutton, X. Li, B. Bryla, G. Schiffman, J. B. Robbins, and R. Schneerson, Infect. Immun. 56:2292-2298, 1988). Adult volunteers, randomized into three groups, were injected either with one of these two conjugates or with Pnu-Imune, the 23 valent pneumococcus vaccine containing 25 micrograms of Pn12F as one of its components. Volunteers were injected two times, 4 weeks apart, with the Pn12F-DT conjugates and once with the Pnu-Imune. Side reactions following injection of the conjugates of Pnu-Imune were mild and short-lived. At 4 weeks and at 7 months after the first injection, higher levels of Pn12F antibodies were found in the volunteers injected with the conjugates than in the Pnu-Imune group (P less than 0.001). The conjugate prepared with the higher-molecular-weight Pn12F elicited higher levels of antibodies than the conjugate prepared with a lower-molecular-weight Pn12F preparation (P = 0.05). Both conjugates elicited about a 13-fold rise in DT antibodies.
对含有糖醛酸的荚膜多糖(CP)、与白喉类毒素(DT)结合的12F型肺炎球菌(Pn12F)偶联物在成年志愿者中的安全性和免疫原性进行了研究。在小鼠中,用同一批次的DT和Pn12F - 40234 - 006(一种高分子量的均质CP)或Pn12 - 812408(一种含有低分子量物质的多分散CP)制备的这些偶联物比单独的Pn12F更具免疫原性,并且具有T细胞依赖性特性(A. Fattom、W. F. Vann、S.C. Szu、A. Sutton、X. Li、B. Bryla、G. Schiffman、J. B. Robbins和R. Schneerson,《感染与免疫》56:2292 - 2298,1988)。成年志愿者被随机分为三组,分别注射这两种偶联物之一或Pnu - Imune(一种23价肺炎球菌疫苗,其成分之一含有25微克Pn12F)。志愿者分别接受两次注射,间隔4周,注射Pn12F - DT偶联物,以及一次注射Pnu - Imune。注射Pnu - Imune或偶联物后的副作用轻微且持续时间短。在首次注射后的4周和7个月时,注射偶联物的志愿者体内的Pn12F抗体水平高于Pnu - Imune组(P < 0.001)。用高分子量Pn12F制备的偶联物比用低分子量Pn12F制备的偶联物诱导产生的抗体水平更高(P = 0.05)。两种偶联物均使DT抗体升高约13倍。