Evaluation of Immune responses to Rotavirus Vaccination in Indian Infants Supplemented with Zinc and Probiotics

Abstract

A statistically significant increase in the immunogenicity of a monovalent rotavirus vaccine, Rotarix®, was generated through combined supplementation with zinc and probiotics in a setting where there is early exposure to rotavirus and immunogenicity is low. At the dosages used in this study, supplementation with zinc or Lactobacillus GG considered separately did not improve seroconversion, although the increase in the proportion of children who seroconverted (7.7%, P=0.066) to Rotarix® following probiotic supplementation was borderline significant. There was a statistically significant increase in the rotavirus vaccine virus shedding in responders compared to non-responders on days 4 and 7 post administration of the first dose of rotavirus vaccine representing active viral replication. Baseline seropositivity was shown to result in a decrease in the levels of shedding indicating a possible neutralizing effect of rotavirus specific IgA or other antibodies not estimated on the replicating vaccine virus. We found high levels of gut and systemic inflammation levels in Indian infants to be associated with lower levels of vaccine virus shedding at one time point in a subset of children. REG1b levels estimated at 6 and 10 weeks of age in Indian infants were higher compared to previous studies done in Bangladesh and Peru. There was no significant correlation seen between serum AGP levels with RV-IgA levels at baseline and post vaccination. However, there was a significant increase in systemic (AGP) levels post vaccination compared to pre-vaccination levels known to be associated with increase with age and stimulation of the adaptive immunity caused by vaccination. A combined ASC response rate of 43.3% was seen in previously exposed or vaccinated children, but this did not correlate with the serum RV-IgA seroconversion data. A higher IgG ASC response was seen in children who had prior exposure to rotavirus before vaccination but a higher IgA ASC response was seen in children as a primary response post-vaccination.