Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior

Abstract

BackgroundIn 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.ObjectivesThe objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model.MethodsWe 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.ResultsWe 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.ConclusionsThis 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.CitationCurtis B, Liberato N, Rulien M, Morrisroe K, Kenney C, Yutuc V, Ferrier C, Marti CN, Mandell D, Burbacher TM, Sackett GP, Hewitson L. 2015. Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior. Environ Health Perspect 123:579–589; http://dx.doi.org/10.1289/ehp.1408257

Animal Models to Study Placental Development and Function throughout Normal and Dysfunctional Human Pregnancy

“…Unlike rodents that are born immature in terms of brain maturation, the rhesus neonate has significantly more white matter at birth, making the rhesus a far better model for assessing neonatal cognitive and behavioral outcomes as a result of adverse pregnancies (e.g., placental insufficiency, fetal growth restriction, and preeclampsia). 55,56 The permeability and placental transfer mechanisms in the rhesus are analogous to human placenta; thus, the efficacy, safety, and pharmacokineticpharmacodynamics of new therapeutic drugs are routinely tested in the rhesus macaque prior to clinical use. [57][58][59][60] Spontaneous preeclampsia has been documented in the rhesus macaque (personal observations) 61 and experimentally induced preeclampsia is achievable in baboons in which all the clinical hallmarks of human preeclampsia are present (e.g., hypertension, proteinuria, and renal histological changes).…”

Regulation of Sirt1/Nrf2/TNF-α signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity

“…Thimerosal is regarded as an irreplaceable ingredient in some pediatric vaccines but, though it is not conclusive, is also thought to contribute to adverse neurobehavioral effects11. Inorganic mercury is also used in cosmetics for skin whitening12.…”

Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status

“…Both positive and negative effects of thimerosal exposure have been reported in several cohort studies 7 – 10 . Importantly, studies analyzing the impact of thimerosal on the neurobehavior and brain development using non-human primate models did not show negative outcomes 11 , 12 . Nonetheless, due to perceived health risks, thimerosal has been removed from most pediatric vaccines in the US, although some multidose vaccines, such as the influenza vaccine and meningococcal vaccine still contain thimerosal 13 .…”