Abstract
Background
Potentially, orally administered antibodies specific to enteric pathogens could be administered to infants to prevent diarrheal infections, particularly in developing countries where diarrhea is a major problem. However, to prevent infection, such antibodies would need to resist degradation within the gastrointestinal tract.
Methods
Palivizumab, a recombinant antibody specific to respiratory syncytial virus (RSV), was used in this study as a model for examining the digestion of neutralizing antibodies to enteric pathogens in infants. The survival of this recombinant IgG1 across digestion in 11 infants was assayed via an anti-idiotype ELISA and RSV F protein-specific ELISA. Concentrations were controlled for any dilution or concentration that occurred in the digestive system using mass spectrometry-based quantification of co-administered, orally supplemented, indigestible polyethylene glycol (PEG-28).
Results
Binding activity of Palivizumab IgG1 decreased (26–99%) across each phase of in vivo digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs.
Conclusion
Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective.
Impact
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Binding activity of palivizumab IgG1 decreased (26–99%) across each phase of in vivo infant digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs.
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Palivizumab was likely degraded by proteases and changes in pH introduced in the gut.
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Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective.
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The monoclonal antibody IgG1 tested was not stable across the infant gastrointestinal tract.
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The observation of palivizumab reduction was unlikely due to dilution in the gastrointestinal tract.
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The results of this work hint that provision of antibody could be effective in preventing enteric pathogen infection in infants.
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Orally delivered recombinant antibodies will need to either be dosed at high levels to compensate for digestive losses or be engineered to better resist digestion.
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Provision of enteric pathogen-specific recombinant antibodies to at-risk infants could provide a new and previously unexplored pathway to reducing the infection in infants.
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The strategy of enteric recombinant antibodies deserves more investigation throughout medicine as a novel means for treatment of enteric disease targets.
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Acknowledgements
The authors thank Matt Paluska, Anahi Y. Torres-Pimentel, Jooyoung Yeo, Siana Liti, and Kimberly R. Lane for their assistance with the ELISA experiments. This study was supported by the Bill & Melinda Gates Foundation (OPP1183649). The authors also acknowledge support from the OSU Mass Spectrometry Center in part through instrumentation grant NIH # 1S10OD020111-01 and the Oregon State University Research Office.
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J.L., B.J.K., V.D.-M., B.N.P.S., Y.W., A.O., M.A., A.O'C., B.P.S., and D.C.D conceptualized the study. J.L. and B.J.K designed the experiments, performed data acquisition, and analyzed data. J.L. drafted the article. D.C.D supervised the experiments. All authors revised, adapted, and approved final version of the manuscript.
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Lueangsakulthai, J., Kim, B.J., Demers-Mathieu, V. et al. Effect of digestion on stability of palivizumab IgG1 in the infant gastrointestinal tract. Pediatr Res 90, 335–340 (2021). https://doi.org/10.1038/s41390-020-01271-y
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DOI: https://doi.org/10.1038/s41390-020-01271-y
