Parke J C
Department of Pediatrics, Charlotte Memorial Hospital and Medical Center, Inc., NC 28232-2861.
Pediatr Infect Dis J. 1987 Aug;6(8):795-8. doi: 10.1097/00006454-198708000-00040.
The inability of infants to respond to Hib PRP with the production of protective antibodies is probably in large part a consequence of the relative immaturity of their immune system. It has been reported that PRP-induced antibodies in adults are primarily of the IgG subclass 2 and that there is a higher frequency of invasive H. influenzae type b diseases among adults with limited antibody deficiencies when the IgG subclass 2 isotype is not present at normal levels. There is evidence that adult levels of IgG subclass 2 are attained later in life than are adult levels of the other subclasses. Regulation of the level of this IgG subclass will undoubtedly be an important determinant in the induction of anti-PRP antibodies in infants. It seems unlikely that simple modification of PRP, such as by increasing molecular size, would result in an increased effectiveness in younger infants, because this group is inherently unable to synthesize subclass 2 antibodies. Currently intensive efforts are being made in several laboratories to develop vaccines that conjugate PRP with proteins that are capable of eliciting a T cell-dependent response in younger children. Preliminary results of several ongoing clinical trials of vaccines of PRP conjugated with diphtheria and with tetanus toxoids indicate that these vaccines are efficacious in children as young as 7 months of age. Researchers are hopeful that vaccines can be developed to protect infants ages 2 to 3 months.
婴儿无法通过产生保护性抗体来对b型流感嗜血杆菌结合疫苗(Hib PRP)作出反应,这在很大程度上可能是其免疫系统相对不成熟的结果。据报道,成人中PRP诱导产生的抗体主要是IgG2亚类,而且在IgG2亚型水平未达到正常水平、存在有限抗体缺陷的成人中,侵袭性b型流感嗜血杆菌疾病的发生率更高。有证据表明,IgG2亚类的成人水平在生命后期才会达到,比其他亚类的成人水平出现得晚。这种IgG亚类水平的调节无疑将是诱导婴儿产生抗PRP抗体的一个重要决定因素。简单改变PRP,比如增加其分子大小,似乎不太可能提高对年幼儿童的有效性,因为这个群体天生就无法合成2亚类抗体。目前,几个实验室正在全力以赴研发将PRP与能够在年幼儿童中引发T细胞依赖性反应的蛋白质结合的疫苗。几项正在进行的PRP与白喉及破伤风类毒素结合疫苗临床试验的初步结果表明,这些疫苗对7个月大的儿童有效。研究人员希望能够研发出保护2至3个月大婴儿的疫苗。