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  5. Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus.

Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus.

File(s)
39842610.pdf (4.67 MB)
No Access Until
1/20/26
Permanent Link(s)
https://hdl.handle.net/1813/116821
Collections
Department of Pediatrics
Author
Langel, S.N.
Otero, C.E.
Steppe, J.T.
Williams, C.A.
Travieso, T.
Chang, J.
Webster, H.
Williamson, L.E.
Crowe, J.E., Jr
Abstract

Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into the infant intestine through breast milk could provide enhanced antimicrobial protection for neonates. Here, we developed a murine model of maternal protective transfer against human rotavirus (RV) using systemic administration of a dimeric IgA monoclonal antibody (mAb). First, we showed that systemically administered dIgA passively transferred into breast milk and the stomach of suckling pups in a dose-dependent manner. Next, we optimized the recombinant production of a potently RV-neutralizing, VP4-specific dIgA (mAb41) antibody. We then demonstrated that systemic administration of dIgA and IgG mAb41 in lactating dams conferred protection from RV-induced diarrhea in suckling pups, with dIgA resulting in lower diarrhea incidence from IgG. Systemic delivery of engineered antimicrobial dIgA mAbs should be considered as an effective strategy for sIgA delivery to the infant gastrointestinal tract via breast milk to increase protection against enteric pathogens.

Journal / Series
Mucosal immunology
Date Issued
1/20/25
Publisher
Elsevier
Keywords
Breast milk
•
Dimeric IgA
•
Maternal immunity
•
Neonatal immunity
•
Passive transfer
•
Rotavirus
•
WCM Library Coordinated Deposit
Related DOI
https://doi.org/10.1016/j.mucimm.2025.01.002
Previously Published as
Langel SN, Otero CE, Steppe JT, Williams CA, Travieso T, Chang J, Webster H, Williamson LE, Crowe JE, Jr., Greenberg HB, Wu H, Hornik CP, Mansouri K, Edwards RJ, Stalls V, Acharya P, Blasi M, Permar SR. Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus. Mucosal Immunol. 2025. Epub 20250120. doi: 10.1016/j.mucimm.2025.01.002. PMID: 39842610.
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Rights URI
https://creativecommons.org/licenses/by-nc-nd/4.0/
Type
article

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