Med Hypotheses. 2011 Dec;77(6):940-7. doi: 10.1016/j.mehy.2011.08.019. Epub 2011 Oct 10.
The first conjugate vaccine was approved for use in the US in 1988 to protect infants and young children against the capsular bacteria Haemophilus influenzae type b (Hib). Since its introduction in the US, this vaccine has been approved in most developed countries, including Denmark and Israel where the vaccine was added to their national vaccine programs in 1993 and 1994, respectively. There have been marked increases in the reported prevalence of autism spectrum disorders (ASDs) among children in the US beginning with birth cohorts in the late 1980s and in Denmark and Israel starting approximately 4-5 years later. Although these increases may partly reflect ascertainment biases, an exogenous trigger could explain a significant portion of the reported increases in ASDs. It is hypothesized here that the introduction of the Hib conjugate vaccine in the US in 1988 and its subsequent introduction in Denmark and Israel could explain a substantial portion of the initial increases in ASDs in those countries. The continuation of the trend toward increased rates of ASDs could be further explained by increased usage of the vaccine, a change in 1990 in the recommended age of vaccination in the US from 15 to 2 months, increased immunogenicity of the vaccine through changes in its carrier protein, and the subsequent introduction of the conjugate vaccine for Streptococcus pneumoniae. Although conjugate vaccines have been highly effective in protecting infants and young children from the significant morbidity and mortality caused by Hib and S. pneumoniae, the potential effects of conjugate vaccines on neural development merit close examination. Conjugate vaccines fundamentally change the manner in which the immune systems of infants and young children function by deviating their immune responses to the targeted carbohydrate antigens from a state of hypo-responsiveness to a robust B2 B cell mediated response. This period of hypo-responsiveness to carbohydrate antigens coincides with the intense myelination process in infants and young children, and conjugate vaccines may have disrupted evolutionary forces that favored early brain development over the need to protect infants and young children from capsular bacteria.
第一种结合疫苗于 1988 年在美国获得批准使用，用于保护婴儿和幼儿免受荚膜细菌流感嗜血杆菌 b（Hib）的侵害。自在美国推出以来，这种疫苗已在包括丹麦和以色列在内的大多数发达国家获得批准，这两个国家分别于 1993 年和 1994 年将该疫苗纳入其国家疫苗计划。自 20 世纪 80 年代末美国出生队列开始，以及大约 4-5 年后丹麦和以色列，儿童自闭症谱系障碍（ASD）的报告患病率显著增加。尽管这些增加可能部分反映了确定偏差，但外源性触发因素可以解释 ASD 报告增加的很大一部分。这里假设，1988 年在美国推出 Hib 结合疫苗及其随后在丹麦和以色列的推出，可以解释这些国家 ASD 最初增加的大部分原因。由于疫苗使用量的增加、美国疫苗接种推荐年龄从 15 个月到 2 个月的变化、疫苗载体蛋白的变化导致疫苗免疫原性的提高以及随后引入肺炎链球菌结合疫苗，ASD 发病率持续上升的趋势可以进一步解释。尽管结合疫苗在保护婴儿和幼儿免受 Hib 和 S. pneumoniae 引起的高发病率和死亡率方面非常有效，但结合疫苗对神经发育的潜在影响值得密切关注。结合疫苗通过将其针对的碳水化合物抗原的免疫反应从低反应状态转变为强大的 B2 B 细胞介导反应，从根本上改变了婴儿和幼儿免疫系统的功能方式。这种对碳水化合物抗原的低反应性与婴儿和幼儿强烈的髓鞘形成过程相吻合，结合疫苗可能破坏了有利于早期大脑发育而不是保护婴儿和幼儿免受荚膜细菌侵害的进化力量。
