Adenovirus 40 and 41 Antibodies Associated With Protection From Infection in a Bangladeshi Birth Cohort

TL;DR

The study found that antibodies to specific adenovirus proteins in early life are linked to protection against future infections in children.

Contribution

The study identifies penton base proteins as novel correlates of protection against adenovirus 40/41 infection.

Findings

Antibodies to AdV 41 penton base at Year 1 reduce infection risk in Year 2.

Higher PB reactivity correlates with milder infections in Year 2.

Penton base proteins are promising targets for vaccines or therapies.

Abstract

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.

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.

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).

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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