Pediatric Vaccines Influence Primate Behavior

From Safeminds.org:

The study is currently in review and has not been published yet.

Pediatric Vaccines Influence Primate Behavior, and Amygdala Growth and Opioid Ligand Binding Friday, May 16, 2008: IMFAR

L. Hewitson , Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA B. Lopresti , Radiology, University of Pittsburgh, Pittsburgh, PA C. Stott , Thoughtful House Center for Children, Austin, TX J. Tomko , Pittsburgh Development Center, University of Pittsburgh, Pittsburgh, PA L. Houser , Pittsburgh Development Center, University of Pittsburgh, Pittsburgh, PA E. Klein , Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA C. Castro , Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA G. Sackett , Psychology, Washington National Primate Research Center, Seattle, WA S. Gupta , Medicine, Pathology & Laboratory Medicine, University of California - Irvine, Irvine, CA D. Atwood , Chemistry, University of Kentucky, Lexington, KY L. Blue , Chemistry, University of Kentucky, Lexington, KY E. R. White , Chemistry, University of Kentucky, Lexington, KY A. Wakefield , Thoughtful House Center for Children, Austin, TX

Background: Macaques are commonly used in pre-clinical vaccine safety testing, but the combined childhood vaccine regimen, rather than individual vaccines, has not been studied. Childhood vaccines are a possible causal factor in autism, and abnormal behaviors and anomalous amygdala growth are potentially inter-related features of this condition.

Objectives: The objective of this study was to compare early infant cognition and behavior with amygdala size and opioid binding in rhesus macaques receiving the recommended childhood vaccines (1994-1999), the majority of which contained the bactericidal preservative ethylmercurithiosalicylic acid (thimerosal).

Methods: Macaques were administered the recommended infant vaccines, adjusted for age and thimerosal dose (exposed; N=13), or saline (unexposed; N=3). Primate development, cognition and social behavior were assessed for both vaccinated and unvaccinated infants using standardized tests developed at the Washington National Primate Research Center. Amygdala growth and binding were measured serially by MRI and by the binding of the non-selective opioid antagonist [11C]diprenorphine, measured by PET, respectively, before (T1) and after (T2) the administration of the measles-mumps-rubella vaccine (MMR).

Results: Compared with unexposed animals, significant neurodevelopmental deficits were evident for exposed animals in survival reflexes, tests of color discrimination and reversal, and learning sets. Differences in behaviors were observed between exposed and unexposed animals and within the exposed group before and after MMR vaccination. Compared with unexposed animals, exposed animals showed attenuation of amygdala growth and differences in the amygdala binding of [11C]diprenorphine. Interaction models identified significant associations between specific aberrant social and non-social behaviors, isotope binding, and vaccine exposure.

Conclusions: This animal model, which examines for the first time, behavioral, functional, and neuromorphometric consequences of the childhood vaccine regimen, mimics certain neurological abnormalities of autism. The findings raise important safety issues while providing a potential model for examining aspects of causation and disease pathogenesis in acquired disorders of behavior and development.

Pediatric Vaccines Influence Primate Behavior, and Brain Stem Volume and Opioid Ligand Binding Saturday, IMFAR

Wakefield , Thoughtful House Center for Children, Austin, TX C. Stott , Thoughtful House Center for Children, Austin, TX B. Lopresti , Radiology, University of Pittsburgh, Pittsburgh, PA J. Tomko , Pittsburgh Development Center, University of Pittsburgh, Pittsburgh, PA L. Houser , Pittsburgh Development Center, University of Pittsburgh, Pittsburgh, PA G. Sackett , Psychology, Washington National Primate Research Center, Seattle, WA L. Hewitson , Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA

Background: Abnormal brainstem structure and function have been reported in children with autism. Opioid receptors play key roles in neuro-ontogeny, are present in brainstem nuclei, and may influence aspects of autism. Childhood vaccines are a possible causal factor in autism and while primates are used in pre-clinical vaccine safety testing, the recommended infant regimen (1994-1999) has not been tested.

Objectives:

The objective of this study was to compare brain stem volume and opioid binding in rhesus infants receiving the recommended infant vaccine regimen.

Methods:

Rhesus macaques were administered vaccines adjusted for age and thimerosal dose (exposed; N=13), or placebo (unexposed; N=3) from birth onwards. Brainstem volume was measured by quantitative MRI, and binding of the non-selective opioid antagonist [11C]diprenorphine (DPN) was measured by PET, at 2 (T1) and 4 (T2) months of age. Neonatal reflexes and sensorimotor responses were measured in standardized tests for 30 days.

Results:

Kaplan-Meier survival analyses revealed significant differences between exposed and unexposed animals, with delayed acquisition of root, suck, clasp hand, and clasp foot reflexes. Interaction models examined possible relationships between time-to-acquisition of reflexes, exposure, [3C]DPN binding, and volume. Statistically significant interactions between exposure and time-to–acquisition of reflex on overall levels of binding at T1 and T2 were observed for all 18 reflexes. For all but one (snout), this involved a mean increase in time-to-acquisition of the reflex for exposed animals. In each model there was also a significant interaction between exposure and MRI volume on overall binding.

Conclusions:

This animal model examines the neurological consequences of the childhood vaccine regimen. Functional and neuromorphometric brainstem anomalies were evident in vaccinated animals that may be relevant to some aspects of autism. The findings raise important safety issues while providing a potential animal model for examining aspects of causation and disease pathogenesis in acquired neurodevelopmental disorders.

Microarray Analysis of GI Tissue in a Macaque Model of the Effects of Infant Vaccination Saturday, May 17, 2008 IMFAR
S. J. Walker , Institute for Regenerative Medicine, Wake Forest University Health Sciences, E. K. Lobenhofer , Cogenics, a Division of Clinical Data E. Klein , Division of Laboratory Animal Resources, University of Pittsburgh, A. Wakefield , Thoughtful House Center for Children, Austin, TX L. Hewitson , Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA

Background: There has been considerable debate regarding the question of an interaction between childhood vaccinations and adverse sequelae in the gastrointestinal tract, immune system, and central nervous system of some recipients. These systems, either singly or in combination, appear to be adversely affected in many ASD children. Although pre-clinical tests of individual vaccines routinely find the risk/benefit ratio to be low, previously there has not been a study to examine the effects of the comprehensive vaccination regime currently in use for infants.

Objectives: This study was designed to evaluate potential alterations in normal growth and development resulting from the vaccine regimen that was in use from 1994-1999. Specifically, this portion of the study was to compare the gene expression profiles obtained from gastrointestinal tissue from vaccinated and unvaccinated infants.

Methods: Infant male macaques were vaccinated (or given saline placebo) using the human vaccination schedule. Dosages and times of administration were adjusted for differences between macaques and humans. Biopsy tissue was collected from the animals at three time points: (1) 10 weeks [pre-MMR1], (2) 14 weeks [post-MMR1] and, (3) 12-15 months [at necropsy]. Whole genome microarray analysis was performed on RNA extracted from the GI tissue from 7 vaccinated and 2 unvaccinated animals at each of these 3 time points (27 samples total).

Results: Histopathological examination revealed that vaccinated animals exhibited progressively severe chronic active inflammation, whereas unexposed animals did not. Gene expression comparisons between the groups (vaccinated versus unvaccinated) revealed only 120 genes differentially expressed (fc >1.5; log ratio p<0.001) at 10 weeks, whereas there were 450 genes differentially expressed at 14 weeks, and 324 differentially expressed genes between the 2 groups at necropsy.

Conclusions: We have found many significant differences in the GI tissue gene expression profiles between vaccinated and unvaccinated animals. These differences will be presented and discussed.

The authors and organizations are withholding comment or elaboration until the full articles are published.