Enteric virome negatively affects seroconversion following oral rotavirus vaccination in a longitudinally sampled cohort of Ghanaian infants
Andrew HyoungJin Kim, George Armah, Francis E. Dennis, Leran Wang, Rachel Rodgers, Lindsay Droit, Megan T. Baldridge, Scott A. Handley, Vanessa Harris
Abstract
Rotavirus 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.