Protective transfer: Maternal passive immunization with a rotavirus-neutralizing dimeric IgA protects against rotavirus disease in suckling neonates

Langel, S. N.; Steppe, J. T.; Chang, J.; Travieso, T.; Webster, H.; Otero, C.; Williamson, L.; Crowe, J. E.; Greenberg, H.; Wu, H.; Hornik, C.; Mansouri, K.; Edward, R.; Stalls, V.; Acharya, P.; Blasi, M.; Permar, S. R.

doi:10.1101/2021.09.21.461116

bioRxiv · 10.1101/2021.09.21.461116

Protective transfer: Maternal passive immunization with a rotavirus-neutralizing dimeric IgA protects against rotavirus disease in suckling neonates

Langel, S. N.·Steppe, J. T.·Chang, J.·Travieso, T.·Webster, H.·Otero, C.·Williamson, L.·Crowe, J. E.·Greenberg, H.·Wu, H.·Hornik, C.·Mansouri, K.·Edward, R.·Stalls, V.·Acharya, P.·Blasi, M.·Permar, S. R.

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Abstract

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. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/461116v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1af34dcorg.highwire.dtl.DTLVardef@1b78cb2org.highwire.dtl.DTLVardef@1760a62org.highwire.dtl.DTLVardef@a3cea2_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Langel, S. N., Steppe, J. T., Chang, J., Travieso, T., Webster, H., Otero, C., Williamson, L., Crowe, J. E., Greenberg, H., Wu, H., Hornik, C., Mansouri, K., Edward, R., Stalls, V., Acharya, P., Blasi, M., Permar, S. R.. 2021-09-23. Protective transfer: Maternal passive immunization with a rotavirus-neutralizing dimeric IgA protects against rotavirus disease in suckling neonates. https://doi.org/10.1101/2021.09.21.461116

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