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

Yu Hasegawa,Megan Rulien,Laura Hewitson,Kristin Watkins,Vernon Yutuc,Chris English,Britni Curtis,Carolyn M Slupsky,Clayton Ferrier,Kelly Morrisroe

doi:10.1038/s41598-018-34019-0

Abstract

Although thimerosal, an ethylmercury-based preservative, has been removed from most pediatric vaccines in the United States, some multidose vaccines, such as influenza vaccines, still contain thimerosal. Considering that a growing number of studies indicate involvement of the gut microbiome in infant immune development and vaccine responses, it is important to elucidate the impact of pediatric vaccines, including thimerosal-containing vaccines, on gut microbial structure and function. Here, a non-human primate model was utilized to assess how two vaccine schedules affect the gut microbiome in infants (5–9 days old) and juveniles (77–88 weeks old) through 16S ribosomal RNA sequencing and metabolomics analyses of the fecal samples. Two treatment groups (n = 12/group) followed either the vaccine schedule that was in place during the 1990s (intensive exposure to thimerosal) or an expanded schedule administered in 2008 (prenatal and postnatal exposure to thimerosal mainly via influenza vaccines), and were compared with a control group (n = 16) that received saline injections. The primary impact on gut microbial structure and function was age. Although a few statistically significant impacts of the two common pediatric vaccine schedules were observed when confounding factors were considered, the magnitude of the differences was small, and appeared to be positive with vaccination.

Highlights

Thimerosal, an ethylmercury (EtHg)-based preservative, has been used in some pediatric vaccines in the United States (US) since the 1930s1
In the 1990s, a number of pediatric vaccines given to infants contained thimerosal, a mercury-based preservative, which led some parent and advocacy groups to question the safety of vaccines because the cumulative thimerosal exposure in some US children was 187.5 μg EtHg by 6 months of age[2]
While thimerosal has generally been removed from most pediatric vaccines, it is still common for US mothers to receive seasonal influenza vaccines during pregnancy that contain thimerosal

Summary

Introduction

Thimerosal, an ethylmercury (EtHg)-based preservative, has been used in some pediatric vaccines in the United States (US) since the 1930s1. While low concentrations of thimerosal and EtHg found in vaccines was reported to be active against cultured brain cells (reviewed in3), data from animal studies was mixed and dependent on the dose of thimerosal used, the mode of administration, as well as methodological differences between studies[4,5,6] Both positive and negative effects of thimerosal exposure have been reported in several cohort studies[7,8,9,10]. Human infants injected with thimerosal-containing vaccines (TCVs) showed detectable mercury in stool samples[18], which suggests that mercury potentially interacts with the gut microbiome. It is not clear whether pediatric vaccines would alter the gut microbiota structure and/or function measured through the fecal metabolome. The impact of TCVs on gut microbial succession in rhesus macaques was studied through analysis of fecal samples obtained from a previous study investigating the effects of pediatric TCVs on neurobehavior and brain development[11,12]

Methods

Results

Conclusion