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Adenovirus 40 and 41 Antibodies Associated With Protection From Infection in a Bangladeshi Birth Cohort
Jennifer Hendrick1, Jennie Z Ma2, Vu Huynh3
1Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
Insights
Higher antibody reactivity to Adenovirus (AdV) penton base (PB) proteins in infants is linked to better protection against severe pediatric gastroenteritis. This suggests AdV PB is a promising target for vaccines and treatments.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Adenovirus (AdV) 40/41 is a leading cause of pediatric acute gastroenteritis (AGE), contributing to global morbidity and mortality.
- Understanding the immune response to AdV 40/41 is crucial for developing effective interventions.
Purpose of the Study:
- To analyze Adenovirus (AdV)-specific antibody reactivities in a Bangladeshi birth cohort.
- To identify clinical correlates of protection against AdV 40/41 infection and disease severity.
Main Methods:
- A multi-AdV protein microarray was used to assess antibody levels against AdV 40, 41, and respiratory AdVs.
- Principal component analysis (PCA) and logistic regression were employed to analyze antibody data from 119 children over two years.
Main Results:
- Antibody reactivity to Adenovirus (AdV) penton base (PB) proteins was a key factor identified by PCA.
- Higher AdV 41 PB antibody reactivity at Year 1 correlated with a reduced risk of AdV 40/41 infection in Year 2.
- Mild to moderate AdV 40/41 infections showed higher AdV PB antibody reactivity compared to severe infections.
Conclusions:
- Elevated antibody reactivity to AdV penton base (PB) proteins is associated with better outcomes in pediatric Adenovirus (AdV) 40/41 infections.
- AdV PB proteins represent a potential target for novel vaccines or monoclonal antibody therapies.
Background:
Adenovirus (AdV) 40/41 is a major cause of pediatric acute gastroenteritis (AGE), leading to significant morbidity and mortality worldwide. As little is known about clinical correlates of protection, we analyzed AdV-specific antibody reactivities using a multi-AdV protein microarray and serum from a Bangladeshi birth cohort surveilled for diarrhea during the first 2 years of life.
Methods:
Arrays contained a comprehensive set of proteins from AdV 40 and 41, in addition to respiratory AdVs 4, 5, and 26. Children were split into four groups according to AdV 40/41 infection occurrence during year 1 (Y1) and year 2 (Y2) of life. One-year array antibody reactivity levels were analyzed from 119 children using principal component analysis (PCA). Top antibody reactivities were evaluated for associations with AdV 40/41 disease severity and protection in Year 2 using logistic regression.
Results:
Eight principal components (PCs) were identified from PCA. Top targets contributing to the leading PCs included external AdV 40/41 antigens that function in host cell entry, particularly penton base (PB) proteins. AdV 41 PB antibody reactivity at Year 1 is significantly associated with reduced risk of AdV 40/41 infection in Year 2 (OR = 0.36, 95% CI: 0.16-0.80, P = .013, adjusted P = .003). Additionally, those with mild to moderate infections in Year 2 had higher reactivities to AdV 40 and 41 PB compared to severe infections (P = .008 and .032, respectively).
Conclusions:
Higher antibody reactivity to AdV PB was associated with improved Year 2 AdV 40/41 outcomes, elevating it as a promising vaccine or monoclonal antibody target.
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