PT  - JOURNAL ARTICLE
AU  - SN Langel
AU  - JT Steppe
AU  - J Chang
AU  - T Travieso
AU  - H Webster
AU  - CE Otero
AU  - LE Williamson
AU  - JE Crowe, Jr
AU  - HB Greenberg
AU  - H Wu
AU  - C Hornik
AU  - K Mansouri
AU  - RJ Edwards
AU  - V Stalls
AU  - P Acharya
AU  - M Blasi
AU  - SR Permar
TI  - Protective Transfer: Maternal passive immunization with a rotavirus-neutralizing dimeric IgA protects against rotavirus disease in suckling neonates
AID  - 10.1101/2021.09.21.461116
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.21.461116
4099  - http://biorxiv.org/content/early/2021/09/23/2021.09.21.461116.short
4100  - http://biorxiv.org/content/early/2021/09/23/2021.09.21.461116.full
AB  - Breast milk secretory IgA antibodies provide a first line of defense against enteric infections. Despite this and an effective vaccine, human rotaviruses (RVs) remain the leading cause of severe infectious diarrhea in children in low- and middle-income countries (LMIC) where vaccine efficacy is lower than that of developed nations. Therapeutic strategies that deliver potently neutralizing antibodies into milk could provide protection against enteric pathogens such as RVs. We developed a murine model of maternal protective-transfer using systemic administration of a dimeric IgA (dIgA) monoclonal antibody. We confirmed that systemically-administered dIgA passively transferred into milk and stomach of suckling pups in a dose-dependent manner. We then demonstrated that systemic administration of an engineered potent RV-neutralizing dIgA (mAb41) in lactating dams protected suckling pups from RV-induced diarrhea. This maternal protective-transfer immunization platform could be an effective strategy to improve infant mortality against enteric infections, particularly in LMIC with high rates of breastfeeding.Competing Interest StatementJ.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received unrelated sponsored research agreements from Takeda Vaccines, IDBiologics and AstraZeneca. S.R.P. provides individual consulting services to Moderna, Merck, Dynavax, and Pfizer. Merck Vaccines and Moderna have provided grants and contracts for S.R.P. sponsored programs.