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Published on: January 28, 2019
Association of Anti-Rotavirus IgA Seroconversion with Growth, Environmental Enteric Dysfunction and Enteropathogens
Sheraz Ahmed1, Junaid Iqbal2, Kamran Sadiq3
1Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan; Institute for Global Health, University of Siena, Italy.
Insights
Oral rotavirus vaccine (RV) effectiveness is low in Pakistani infants due to environmental enteric dysfunction (EED). Healthy growth, IGF-1, AGP, and rotavirus shedding correlate with successful RV vaccine seroconversion.
Area of Science:
- Pediatric Infectious Diseases
- Vaccinology
- Global Health
Background:
- Oral vaccine underperformance in low- and middle-income countries is linked to environmental enteric dysfunction (EED).
- Investigating factors influencing oral rotavirus vaccine (Rotarix®) immunogenicity in Pakistani infants is crucial for improving vaccine efficacy.
Purpose of the Study:
- To evaluate the association between rotavirus vaccine seroconversion and growth, EED biomarkers, and intestinal pathogens in Pakistani infants.
- To identify factors predictive of successful rotavirus vaccine immune response in a high-risk population.
Main Methods:
- A longitudinal, community-based study involving 391 infants receiving two doses of rotavirus vaccine.
- Measurement of serum anti-rotavirus immunoglobulin A (IgA), EED biomarkers (e.g., MPO, AGP), and enteropathogens at enrollment and nine months.
- Statistical analysis including univariate and multivariable logistic regression to identify factors associated with seroconversion.
Main Results:
- 45% of infants achieved seroconversion after vaccination; non-seroconverters exhibited poorer growth parameters.
- Higher insulin-like growth factor (IGF-1) and lower myeloperoxidase (MPO) concentrations were observed in seroconverters.
- Alpha-1 acid glycoprotein (AGP) and IGF-1 concentrations at six months were positively associated with seroconversion; rotavirus shedding favored seroconversion, while sapovirus presence was linked to non-seroconversion.
Conclusions:
- High baseline rotavirus seropositivity and impaired vaccine immunogenicity were noted in this high-risk cohort.
- Healthy growth, serum IGF-1, AGP, and rotavirus shedding are positively associated with rotavirus vaccine IgA seroconversion.
- Sapovirus detection correlated with a lack of seroconversion, highlighting the impact of co-infections on oral vaccine response.
Background:
The underperformance of oral vaccines in children of low- and middle-income countries is partly attributable to underlying environmental enteric dysfunction (EED).
Methodology:
We conducted a longitudinal, community-based study to evaluate the association of oral rotavirus vaccine (Rotarix®) seroconversion with growth anthropometrics, EED biomarkers and intestinal enteropathogens in Pakistani infants. Children were enrolled between three to six months of their age based on their nutritional status. We measured serum anti-rotavirus immunoglobulin A (IgA) at enrollment and nine months of age with EED biomarkers and intestinal enteropathogens.
Results:
A total of 391 infants received two doses of rotavirus (RV) vaccine. 331/391 provided paired blood samples. Of these 331 children, 45% seroconverted at 9 months of age, 35% did not seroconvert and 20% were seropositive at baseline. Non-seroconverted children were more likely to be stunted, wasted and underweight at enrollment. In univariate analysis, insulin-like growth factor (IGF) concentration at 6 months were higher in seroconverters, median (25th, 75th percentile): 26.3 (16.5, 43.5) ng/ml vs. 22.5 (13.6, 36.3) ng/ml for non-seroconverters, p-value = 0.024. At nine months, fecal myeloperoxidase (MPO) concentrations were significantly lower in seroconverters, 3050(1250, 7587) ng/ml vs. 4623.3 (2189, 11650) ng/ml in non-seroconverted children, p-value = 0.017. In multivariable logistic regression analysis, alpha-1 acid glycoprotein (AGP) and IGF-1 concentrations were positively associated with seroconversion at six months. The presence of sapovirus and rotavirus in fecal samples at the time of rotavirus administration, was associated with non-seroconversion and seroconversion, respectively.
Conclusion:
We detected high baseline RV seropositivity and impaired RV vaccine immunogenicity in this high-risk group of children. Healthy growth, serum IGF-1 and AGP, and fecal shedding of rotavirus were positively associated with RV IgA seroconversion following immunization, whereas the presence of sapovirus was more common in non-seroconverters.
Trial Registration:
Clinical Trials ID: NCT03588013.
