Enterovirus and gut virome profile in Indian infants and immune response to oral rotavirus vaccine

Abstract

Background: Oral vaccines such as oral poliovirus vaccine and oral rotavirus vaccine perform suboptimally in low-and-middle income settings such as India. Asymptomatic infection with enteric viruses is associated with impaired immune response to OPV. Whether there is similar interference of asymptomatic presence of enteric viruses with response to other live viral vaccines such as oral rotavirus vaccine (ORV) is unclear. Methods and materials: We included stool samples collected at/before dose 1 and 2 of Rotarix™ from south Indian infants participating in a study evaluating the role of the bacterial gut microbiome in ORV (Rotarix) response. Serum anti-rotavirus IgA levels were measured at 6 weeks age before administration of first ORV dose and at 14 weeks age, 4 weeks after second ORV dose. Shedding of Rotarix vaccine virus was assessed at 7 weeks and 10 weeks of age (1 week after dose 1 ORV and dose 2 ORV, respectively). Enterovirus (EV) infection and carriage was detected from stool samples collected on the day of ORV administration (dose 1 at 6 weeks age and dose 2 at 10 weeks age) from N = 101 infants at 6 and 10 weeks by pan-Enterovirus qPCR targeting the 5′ UTR region followed by shotgun metagenomic NGS for profiling EV serotypes and the gut virome. Bioinformatic analysis was performed using the ViromeScan pipeline with a specifically created database including most enterovirus serotypes. Results: At 6 weeks age, 27.72% (28/101) of all infants were positive for enterovirus carriage while at 10 weeks age, 16.83% (17/101) of all infants were positive for the pan-EV target (5′ UTR). Infants harboring non-polio enteroviruses (NPEV) had significantly higher odds of remaining seronegative to ORV (Odds ratio = 2.53; 95% CI 1.02–6.51), p = 0.03 when compared to infants free of NPEV at both time points. 39 different non-polio enterovirus serotypes were detected in 6–10 week infants with Echovirus-14 and Coxsackievirus-A4 being the commonest serotypes. Conclusion: Infection with NPEV serotypes at the time of any of the two ORV doses has an inhibitory effect on the seroresponse to ORV but is not confined to any particular NPEV serotype.