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

Robin Penugula Lazarus, (2015) Evaluation of Immune responses to Rotavirus Vaccination in Indian Infants Supplemented with Zinc and Probiotics. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.

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Abstract

1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. REG1b levels estimated at 6 and 10 weeks of age in Indian infants were higher compared to previous studies done in Bangladesh and Peru using a similar method to estimate REG1b levels. 7. 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. 8. 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. 9. 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. IMPACT OF THE STUDY: In 2011, the number of deaths was estimated to 6.9 million among children <5 years of age, of which diarrhea accounted for 9.9% (712,000) of these deaths, of which an estimated 27.8% deaths was due to RV resulting in 23 children dying due to this condition every hour (80, 82). India accounts for nearly 13-22% of the estimated RV associated deaths worldwide, with a mortality rate of 8 per 1000 live births (1, 2). Estimates suggest 11.3 million episodes (8394 episodes per 100,000 children) of RV diarrhea occur each year with 1,427 hospitalizations per 100,000 children (88%) in children <2 years of age and 643 hospitalizations per 100,000 in children <5 years of age (2). The WHO has included vaccine research in developing countries against RV as one of its global priorities, even as it includes recommendations for use of licensed vaccines in all countries. Although licensed oral RV vaccines are available, the efficacy and immunogenicity has been comparatively low in developing countries with high under 5 mortality rates. Comprehensive studies investigating immune response to rotavirus vaccination have been attempted to understand factors affecting immunogenicity of a live oral vaccine in a setting where the vaccines appear to perform poorly. Results of the studies reported here showed a combined supplementation with zinc and probiotics results in a significant increase in the immunogenicity of a monovalent RV vaccine, Rotarix®. Estimation of vaccine shedding levels as a proxy for vaccine uptake and replication with the use of qPCR provides a clearer understanding of the low immunogenicity rates seen in low income countries with high RV burden. The study observed that factors such as OPV interference and high level of systemic and gut inflammation seen in Indian infants’ results in diminished performance of the vaccine. An attempt has been made to establish methods to examine cell mediated immunity following RV vaccination. The data generated by these studies have created a foundation for further large scale studies that will enhance our understanding of the immune responses and the performance of these vaccines that may lead to ways to improve the efficacy of live oral RV vaccines in developing countries.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: Immune responses, Rotavirus Vaccination, Indian Infants, Supplementation, Zinc, Probiotics.
Subjects: Respiratory Medicine > Gastroenterology
> Respiratory Medicine > Gastroenterology
Depositing User: Subramani R
Date Deposited: 19 Aug 2017 09:16
Last Modified: 01 Nov 2022 02:06
URI: http://repository-tnmgrmu.ac.in/id/eprint/2703

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