Metagenomic sequencing of stool samples in Bangladeshi infants: virome association with poliovirus shedding after oral poliovirus vaccination

Abstract

The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log10 vs. 2.25 log10, p = 0.002), particularly from potential viral pathogens (2.78log10 vs. 0.83log10, p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus shedding. Following vaccination, 28.6% of 14 infants tested developed neutralizing antibodies to all three Sabin types and also exhibited higher rates of poliovirus shedding (p = 0.020). No vaccine-derived poliovirus variants were detected. These results reveal an inverse association between eukaryotic virome abundance and poliovirus shedding. Overall gut virome ecology and concurrent viral infections may impact oral vaccine responsiveness in Bangladeshi infants.

The gut virome of healthy children during the first year of life is diverse and dynamic

“…It is of upmost importance to understand the way the enteric virome develops during infancy and what impact on the development of the gastrointestinal tract and the human health it may have. Few studies have described the gut virome of infants during the first year of life [12, 13, 15-19, 21, 43-45, 49], with even fewer studies carried out in healthy children, in the community [13,[16][17][18]21]; only four of these studies have been longitudinal [16,19,20,22]. In this work, we characterized the monthly gastrointestinal virome, prokaryotic and eukaryotic, of three healthy infants during their first year of life.…”

“…In our study, members of the Anelloviridae family were highly abundant, containing different species of torque teno mini virus and unclassified species in up to 80% of the samples. In previous studies, viruses from this family have been identified as the most abundant and frequent in healthy children [14, 15, 17-19, 22-24, 50, 51], being more abundant during the first year of life [16,17,22,24], after which the abundances decrease. Their presence has been associated with a reduced host immune status; a higher abundance have been reported in patient with lung transplantation [52,53], AIDs [54], pulmonary diseases [55,56], cancer [57], among others; although their role in the pathogenesis of these diseases remains unclear [58].…”

“…[16] and suggest that infants come more in contact with these viruses a few months after birth, from an unknown source. Viruses in the Picornaviridae family have also been frequently found in healthy children [14,[19][20][21][22][23]50], even in Tan et. al [22] picornaviruses represented the vast majority of reads (93.6%).…”

“…Viruses in the Picornaviridae family have also been frequently found in healthy children [14,[19][20][21][22][23]50], even in Tan et. al [22] picornaviruses represented the vast majority of reads (93.6%). In our study, this family was identified in 80% of the infant samples, with parechovirus A and enterovirus A being the most common species.…”

“…Moreover, other factors as birth delivery mode and feeding type have been identified to affect the diversity of bacteriophages [12,15,18,19]. Regarding eukaryotic viruses in healthy infants [13,15,16,[18][19][20][21][22], they have been identified sporadically, being less frequent in the first xx months of life and increasing in frequency with age. Viruses known to cause illness, from Adenoviridae, Anelloviridae, Astroviridae, Parvoviridae, Picornaviridae, Picobirnaviridae and Reoviridae families, have been commonly identified in infant stool samples, even in the absence of clinical symptoms [13,16,18,20,[22][23][24].…”