038 - Rotavirus Vaccine Responses as a Function of Infant Gut Microbiome and Breastmilk Exposure.

Publication Number: 38.6368

Janiret Narvaez Miranda, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States; Michael B. Sohn, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States; Daniel Velasquez-Portocarrero, CDC - Centers For Disease Control and Prevention, Atlanta, GA, United States; Ann Lindley. Gill, University of Rochester Medical Center, Rochester, NY, United States; Baoming Jiang, CDC, Atlanta, GA, United States; Tom O'Connor, University of Rochester, Rochester, NY, United States; Steven Gill, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States; Kristin M. Scheible, University of Rochester, Rochester, NY, United States

Background: Rotavirus infection accounts for 28% of deaths globally due to diarrheal diseases in children under five years of age. Since the introduction of live attenuated oral rotavirus vaccines (ORV) in 2006, the disease burden has been reduced by 40% worldwide. However, the immunogenicity of these vaccines varies by region, with developed countries reporting higher immunogenicity compared to still developing countries. The factors contributing to variation in ORV’s immunogenicity remain unclear. Still, interactions between replicating virus and the developing infant gut microbiome (IGMb) may play a role, either directly or indirectly, through metabolism- and immune-altering exposures such as the mother’s breast milk (MBM). Previous studies associating IGMb with ORV responses have had mixed results, but have not adequately addressed confounders such as MBM; feeding practices may account for some of the observed variation.

Objective: We aim to test the hypothesis that among a healthy cohort of children from a similar region, variability in Rotavirus-specific responses is partly explained by infant gut microbiome, and this association is modified by breastfeeding.

Design/Methods: Seventy infants were followed from birth through the first year of life. The IGMb was characterized through 16S rRNA sequencing at various time points: at birth, and at one, six, and twelve months of age. ORV immunogenicity was detected using ELISA for Rotavirus-specific IgA (RV-IgA) at birth, six months, and twelve months. Clinical information collected included feeding modes, antibiotic exposure, post-conceptual age, and details regarding Rotavirus vaccination.

Results: Of the full 70 subjects, 59 (84%) were RV-IgA seropositive (titer ≥ 40) at six months. RV-IgA titers ranged from 0-10,240 across all time points (median: 320). IGMb alpha diversity of exclusively breastfed infants at six months of age was associated with increased RV-IgA titers at month six (est=2.469, 95% CI: 0.775, 4.165). Feeding mode (breastmilk or no breastmilk) altered the IGMb beta diversity (overall composition) and did not predict RV-IgA titers at six months.

Conclusion(s): In a healthy infant population in Rochester, New York, seropositivity for RV-IgA is high with variable levels observed. Higher microbiome diversity is associated with higher RV-IgA titers. While MBM exposure does not appear to directly affect RV-IgA titers, it may be a covariate in the relationship between IGMb and RV-IgA due to its significant impact on the developing IGMb.

Microbiome Alpha Diversity Associated with RV-IgA Titers
Figure 1: Association between Microbiome Alpha Diversity and RV-IgA Titers. Each panel illustrates the association between microbiome alpha diversity, measured using the Shannon index, based on different feeding modes at six months, and RV-IgA titers at the same age. Linear regression modeling was employed to assess these associations while controlling for relevant covariates (i.e., vaccination status, post-conceptual age, solid food introduction).