Rotavirus Vaccine Performance: Timing of Doses and Seroconversion in El Alto, Bolivia Open Access

Abstract

 

Rotavirus is a leading cause of diarrheal illness among children globally. Vaccination is the best line of protection against rotavirus infection; however, vaccine effectiveness is lower in low-income settings. One hypothesis states that higher levels of circulating rotavirus in these settings may increase maternal antibodies, which interfere with infants’ immune response to the vaccine. Supporting this hypothesis, randomized controlled trials have found that vaccine protection may be improved through a delayed vaccine schedule, but results are inconsistent. There is a need to better understand the influence of timing on vaccine effectiveness in order to provide optimal protection against severe diarrheal illness in children. This analysis seeks to determine whether the timing (with respect to infant age) of each dose of RV1 affects the serological response in a cohort of vaccinated infants. This analysis uses data from a population of 309 infants who received two doses of the monovalent rotavirus vaccine, Rotarix (RV1), in the Infant Nutrition, Immunology, and Diarrhea study conducted in El Alto, Bolivia in 2013 – 15. Geometric mean titers (GMTs) for rotavirus-specific IgA were obtained from infant blood samples collected prior to the first dose of RV1 and ~2 months following the second dose. Seroconversion was defined as a 4-fold increase in GMT between blood draws. The effect of the timing of RV1 administration on immunogenic response was assessed using log-binomial models and Spearman’s Rank correlations. There were no statistically significant associations between any of the timing exposures (infant age at Dose 1, infant age at Dose 2, and the length of interval between doses) and the immunological outcomes (seroconversion and the fold-change in GMT). However, as a general trend those infants with a longer interval and later second dose were less likely to seroconvert (Risk ratios and 95% Confidence Intervals for a one week increase in each timing variable were 0.96 [0.91, 1.00] for age at Dose 2 and 0.96 [0.92, 1.00] for the length of interval). These findings uphold the current guidelines for vaccine scheduling in Bolivia and do not indicate improved vaccine effectiveness through delayed vaccination.

Table of Contents

REVIEW OF THE LITERATURE .............  1

METHODS ........................................ 12

RESULTS ......................................... 18

DISCUSSION .................................... 22

PUBLIC HEALTH IMPLICATIONS .......... 29

REFERENCES .................................... 30

TABLES ............................................ 40

FIGURES .......................................... 42

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology Health Sciences, Immunology
Keyword	Immune response Schedule Vaccination Vaccine effectiveness Rotavirus Seroconversion Timing
Committee Chair / Thesis Advisor	Leon, Juan, Emory University
Committee Members	Burke, Rachel, CDC
Partnering Agencies	Does not apply (no collaborating organization)

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