Key result
Maternal systemic administration of a rotavirus-neutralizing dimeric IgA (mAb41) reduced the incidence of rotavirus-induced diarrhea in suckling pups to 7.1% compared to 88% with saline.
Why the study?
Rotaviruses remain a leading cause of severe infectious diarrhea in children in low- and middle-income countries with lower vaccine efficacy, creating a need for therapeutic strategies that deliver potently neutralizing antibodies into breast milk.
Does systemic administration of a rotavirus-neutralizing dimeric IgA in lactating dams protect suckling pups from rotavirus-induced diarrhea?
Does systemic administration of a rotavirus-neutralizing dimeric IgA in lactating dams protect suckling pups from rotavirus-induced diarrhea?
Absolute Event Rate: 7.1% vs 88%
Maternal systemic administration of a rotavirus-neutralizing dimeric IgA monoclonal antibody can passively transfer into breast milk and protect suckling neonates from rotavirus disease in a murine model.
Supports maternal dIgA transfer in a murine model; leaves open translation to human neonates.
SUMMARY 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.
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Langel et al. (2021) studied Rotavirus-induced diarrhea. mAb41 dIgA (rotavirus-neutralizing dimeric IgA) vs. Saline was evaluated on Incidence of rotavirus-induced diarrhea in suckling pups. Maternal systemic administration of a rotavirus-neutralizing dimeric IgA (mAb41) reduced the incidence of rotavirus-induced diarrhea in suckling pups to 7.1% compared to 88% with saline.
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