Adenovirus 40 and 41 antibodies associated with protection from infection in a Bangladeshi birth cohort.

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=0.013, adjusted p=0.003). Additionally, those with mild to moderate infections in Year 2 had higher reactivities to AdV 40 and 41 PB compared to severe infections (p=0.008 and 0.032, 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.