Abstract
SummaryRotavirus vaccines (RVVs) have substantially diminished mortality from severe rotavirus (RV) gastroenteritis but are significantly less effective in low- and middle-income countries (LMICs), limiting their life-saving potential. The etiology of RVV’s diminished effectiveness remains incompletely understood, but the enteric microbiota has been implicated in modulating immunity to RVVs. Here, we analyze the enteric microbiota in a longitudinal cohort of 122 Ghanaian infants, evaluated over the course of 3 Rotarix vaccinations between 6 and 15 weeks of age, to assess whether bacterial and viral populations are distinct between non-seroconverted and seroconverted infants. We identify bacterial taxa including Streptococcus and a poorly classified taxon in Enterobacteriaceae as positively correlating with seroconversion. In contrast, both bacteriophage diversity and detection of Enterovirus B and multiple novel cosaviruses are negatively associated with RVV seroconversion. These findings suggest that virome-RVV interference is an underappreciated cause of poor vaccine performance in LMICs.
Highlights
Rotavirus (RV) is the leading cause of diarrheal mortality among children globally (GBD 2016 Causes of Death Collaborators, 2017; GBD 2016 Diarrhoeal Disease Collaborators, 2018)
Enterovirus B and novel Cosavirus A are associated with a lack of seroconversion Because enteroviruses and oral poliovirus vaccine (OPV) strains have previously been implicated in limiting rotavirus vaccines (RVVs) efficacy, we closely examined the Picornaviridae family in our cohort (Figure 6) (Parker et al, 2018b; Patel et al, 2012; Taniuchi et al, 2016)
We found that numerous components of the human microbiota, including specific bacterial taxa, bacteriophage diversity, and known and novel eukaryotic viruses, correlate significantly with RVV immunogenicity in early life, underscoring the importance of the microbiota in determining early human immune responses to enteric pathogens and oral vaccines
Summary
Rotavirus (RV) is the leading cause of diarrheal mortality among children globally (GBD 2016 Causes of Death Collaborators, 2017; GBD 2016 Diarrhoeal Disease Collaborators, 2018). Numerous live, attenuated oral rotavirus vaccines (RVVs) have been licensed for use since 2006, and their introduction in more than 100 countries has helped to substantially decrease RV deaths from more than 500,000 prior to vaccine introduction to approximately 120,000 deaths per year in children under five years of age (Li et al, 2021a; Troeger et al, 2018; ROTA Council, 2020) Despite this enormous public health accomplishment, the potential of RVVs has been limited by their diminished performance in low- and middle-income countries (LMICs). This underscores the urgent public health need to understand and improve RVV performance in LMICs
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