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A Drug-Free Pathogen Capture and Neutralizing Nasal Spray to Prevent Emerging Respiratory Infections

View ORCID ProfileJohn Joseph, Helna Mary Baby, Joselyn Rojas Quintero, Devin Kenney, Yohannes A Mebratu, Eshant Bhatia, Purna Shah, Kabir Swain, Shahdeep Kaur, Xiang-Ling Li, John Mwangi, Olivia Snapper, Remya Nair, Eli Agus, Sruthi Ranganathan, Julian Kage, Jingjing Gao, View ORCID ProfileJames N Luo, Anthony Yu, Florian Douam, View ORCID ProfileYohannes Tesfaigzi, Jeffrey M Karp, Nitin Joshi
doi: https://doi.org/10.1101/2023.10.02.560602
John Joseph
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Harvard Medical School, Boston, MA 02115, USA
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  • ORCID record for John Joseph
Helna Mary Baby
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Joselyn Rojas Quintero
3Harvard Medical School, Boston, MA 02115, USA
4Division of Pulmonology, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Devin Kenney
5National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA
6Department of Microbiology, Boston University, Chobanian & Avedisian School of Medicine, Boston, MA, USA
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Yohannes A Mebratu
3Harvard Medical School, Boston, MA 02115, USA
4Division of Pulmonology, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Eshant Bhatia
7Indian Institute of Technology, Mumbai, India
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Purna Shah
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Kabir Swain
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Shahdeep Kaur
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Harvard Medical School, Boston, MA 02115, USA
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Xiang-Ling Li
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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John Mwangi
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Olivia Snapper
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Remya Nair
3Harvard Medical School, Boston, MA 02115, USA
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Eli Agus
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Sruthi Ranganathan
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Julian Kage
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Jingjing Gao
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Harvard Medical School, Boston, MA 02115, USA
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James N Luo
3Harvard Medical School, Boston, MA 02115, USA
8Department of Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Anthony Yu
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Harvard Medical School, Boston, MA 02115, USA
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Florian Douam
5National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA
6Department of Microbiology, Boston University, Chobanian & Avedisian School of Medicine, Boston, MA, USA
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Yohannes Tesfaigzi
3Harvard Medical School, Boston, MA 02115, USA
4Division of Pulmonology, Brigham and Women’s Hospital, Boston, MA 02115, USA
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  • For correspondence: ytesfaigzi@bwh.harvard.edu jmkarp@bwh.harvard.edu njoshi@bwh.harvard.edu
Jeffrey M Karp
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Harvard Medical School, Boston, MA 02115, USA
9Harvard–Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
10Broad Institute, Cambridge, MA 02142, USA
11Harvard Stem Cell Institute, Cambridge, MA 02138, USA
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  • For correspondence: ytesfaigzi@bwh.harvard.edu jmkarp@bwh.harvard.edu njoshi@bwh.harvard.edu
Nitin Joshi
1Center for Accelerated Medical Innovation, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Center for Nanomedicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
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  • For correspondence: ytesfaigzi@bwh.harvard.edu jmkarp@bwh.harvard.edu njoshi@bwh.harvard.edu
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Abstract

Respiratory infections pose a global health crisis. Vaccines are pathogen specific, and new vaccines are needed for mutants and emerging pathogens. Here, we report a “drug free” prophylactic platform - a “Pathogen Capture and Neutralizing Spray” (PCANS) that acts via a multi-pronged approach to prevent a broad spectrum of respiratory infections. PCANS forms a protective coating in the nasal cavity that enhances the capture of large respiratory droplets. The coating acts as a physical barrier against a broad spectrum of viruses and bacteria, and rapidly neutralizes them, reducing the pathogen load by >99.99%. In mice, PCANS showed nasal retention for at least 8 h and was safe for daily administration. A single prophylactic dose of PCANS protected mice against supra-lethal dosages of a mouse-adapted H1N1 Influenza virus (PR8), reduced lung viral titer by >99.99%, improved survival, and suppressed pathological manifestations. Together, our data suggest PCANS as a promising daily-use prophylactic approach against current and emerging respiratory infections.

Competing Interest Statement

J.J., H.M.B, Y.T., and J.M.K have one pending patent based on the PCANS formulation described in this manuscript. N.J. and J.M.K are paid consultants, scientific advisory board members, and hold equity in Akita Bio, a company that has licensed IP generated by N.J. that may benefit financially if the IP is further validated. The interests of N.J. were reviewed and are subject to a management plan overseen by his institution in accordance with its conflict of interest policies. J.M.K has been a paid consultant and or equity holder for multiple companies (listed here: https://www.karplab.net/team/jeff-karp).

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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A Drug-Free Pathogen Capture and Neutralizing Nasal Spray to Prevent Emerging Respiratory Infections
John Joseph, Helna Mary Baby, Joselyn Rojas Quintero, Devin Kenney, Yohannes A Mebratu, Eshant Bhatia, Purna Shah, Kabir Swain, Shahdeep Kaur, Xiang-Ling Li, John Mwangi, Olivia Snapper, Remya Nair, Eli Agus, Sruthi Ranganathan, Julian Kage, Jingjing Gao, James N Luo, Anthony Yu, Florian Douam, Yohannes Tesfaigzi, Jeffrey M Karp, Nitin Joshi
bioRxiv 2023.10.02.560602; doi: https://doi.org/10.1101/2023.10.02.560602
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A Drug-Free Pathogen Capture and Neutralizing Nasal Spray to Prevent Emerging Respiratory Infections
John Joseph, Helna Mary Baby, Joselyn Rojas Quintero, Devin Kenney, Yohannes A Mebratu, Eshant Bhatia, Purna Shah, Kabir Swain, Shahdeep Kaur, Xiang-Ling Li, John Mwangi, Olivia Snapper, Remya Nair, Eli Agus, Sruthi Ranganathan, Julian Kage, Jingjing Gao, James N Luo, Anthony Yu, Florian Douam, Yohannes Tesfaigzi, Jeffrey M Karp, Nitin Joshi
bioRxiv 2023.10.02.560602; doi: https://doi.org/10.1101/2023.10.02.560602

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