International Meeting for Autism Research (London, May 15-17, 2008): Microarray Analysis of GI Tissue in a Macaque Model of the Effects of Infant Vaccination

Saturday, May 17, 2008

Champagne Terrace/Bordeaux (Novotel London West)

S. J. Walker , Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC

E. K. Lobenhofer , Cogenics, a Division of Clinical Data

E. Klein , Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA

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.

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