ethics approval Patients were studied following informed consent, and with University of Virginia Health Sciences Institutional Review Board (IRB#15832) and FDA (BB- IND #15134) approval. Animals were housed and bred in pathogen- free facilities and used between 6 and 22 weeks of age. The University of Virginia Animal Care and Use Committee approved all procedures. Experiments were carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Provenance and peer review Not commissioned; externally peer reviewed. data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplementary information. All relevant data generated or analyzed during this study are included in this published article (and its online supplementary information files). Additional data generated from the clinical trial during the current study are available from the corresponding author on reasonable request. open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non- commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non- commercial. See http:// creativecommons. org/ licenses/ by- nc/ 4.