Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior

Environ Health Perspect. 2015 Jun;123(6):579-89. doi: 10.1289/ehp.1408257. Epub 2015 Feb 18.

Abstract

Background: 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.

Objectives: The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • Immunization Schedule*
  • Learning / drug effects*
  • Macaca mulatta
  • Male
  • Models, Animal
  • Neurodevelopmental Disorders / chemically induced*
  • Neurotoxins / adverse effects
  • Neurotoxins / toxicity
  • Preservatives, Pharmaceutical / adverse effects
  • Preservatives, Pharmaceutical / pharmacology
  • Social Behavior*
  • Thimerosal / adverse effects*
  • Thimerosal / pharmacology
  • Vaccines / adverse effects*
  • Vaccines / pharmacology

Substances

  • Neurotoxins
  • Preservatives, Pharmaceutical
  • Vaccines
  • Thimerosal