Curtis Britni, Liberato Noelle, Rulien Megan, Morrisroe Kelly, Kenney Caroline, Yutuc Vernon, Ferrier Clayton, Marti C Nathan, Mandell Dorothy, Burbacher Thomas M, Sackett Gene P, Hewitson Laura
Infant Primate Research Laboratory, Washington National Primate Research Center, Seattle, Washington, USA.
Environ Health Perspect. 2015 Jun;123(6):579-89. doi: 10.1289/ehp.1408257. Epub 2015 Feb 18.
In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today.
The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model.
We administered vaccines to six groups of infant male rhesus macaques (n = 12-16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles-mumps-rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate.
We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors.
This comprehensive 5-year case-control study, which closely examined the effects of pediatric vaccines on early primate development, provided no consistent evidence of neurodevelopmental deficits or aberrant behavior in vaccinated animals.
在20世纪90年代，大多数儿科疫苗使用含汞防腐剂硫柳汞。尽管目前仅推荐两种含硫柳汞疫苗（TCV）用于儿科，但家长认为疫苗存在安全问题，这影响了疫苗接种率，尤其是考虑到如今实施的疫苗接种计划范围更广且更为复杂。
本研究的目的是在非人类灵长类动物模型中检验儿科疫苗接种计划的安全性。
我们在适当情况下使用标准化硫柳汞剂量，对六组雄性恒河猴幼崽（每组n = 12 - 16）接种疫苗。研究组包括20世纪90年代推荐的儿科疫苗接种计划、有或无麻疹 - 腮腺炎 - 风疹（MMR）疫苗的加速版20世纪90年代灵长类动物接种计划、仅接种MMR疫苗以及2008年扩展版接种计划。我们对年龄匹配的对照动物（n = 16）注射生理盐水。通过检查新生儿反射的获得、客体概念永久性（OCP）的发展、辨别学习的计算机化测试以及幼崽社交行为，对出生至12个月大的幼崽发育情况进行评估。在适当情况下，使用方差分析、多水平建模和生存分析对数据进行分析。
我们观察到在OCP的获得方面没有组间差异。在辨别学习过程中，接受TCV的动物在逆向测试中表现有所改善，尽管其中一些动物在随后的学习集测试中表现较差。对社交和非社交行为的分析表明，在整个婴儿期几乎没有负面行为的情况。尽管在2个月大时报告了某些特定行为的组间差异，但到12个月时，所有婴儿，无论疫苗接种状况如何，都已发展出恒河猴典型的行为模式。
这项为期5年的全面病例对照研究密切检查了儿科疫苗对灵长类动物早期发育的影响，未提供一致证据表明接种疫苗的动物存在神经发育缺陷或异常行为。
