http://www.ageofautism.com/2008/05/pediatric-vacci.html

AGE OF AUTISM
Editor: Dan Olmsted
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05/16/2008
PEDIATRIC VACCINES INFLUENCE PRIMATE BEHAVIOR: ABSTRACTS
POSTED WITH PERMISSION

This piece accompanies Dan Olmsted's "Sick Monkeys" piece.
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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.

allObjectives: 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.
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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.
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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.