Nebulized mRNA‐Encoded Antibodies Protect Hamsters from SARS‐CoV‐2 Infection
Abstract
Despite the success of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccines, there remains a clear need for new classes of preventatives for respiratory viral infections due to vaccine hesitancy, lack of sterilizing immunity, and for at‐risk patient populations, including the immunocompromised. While many neutralizing antibodies have been identified, and several approved, to treat COVID‐19, systemic delivery, large doses, and high costs have the potential to limit their widespread use, especially in low‐ and middle‐income countries. To use these antibodies more efficiently, an inhalable formulation is developed that allows for the expression of mRNA‐encoded, membrane‐anchored neutralizing antibodies in the lung to mitigate SARS‐CoV‐2 infections. First, the ability of mRNA‐encoded, membrane‐anchored, anti‐SARS‐CoV‐2 antibodies to prevent infections in vitro is demonstrated. Next, it is demonstrated that nebulizer‐based delivery of these mRNA‐expressed neutralizing antibodies potently abrogates disease in the hamster model. Overall, these results support the use of nebulizer‐based mRNA expression of neutralizing antibodies as a new paradigm for mitigating respiratory virus infections.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 31, 2022
- Source ID
- 10.1002/advs.202202771
Entities
People
- Aaron W. Lifland
- Alicia K. Olivier
- Barton Haynes
- Chiara Zurla
- Dapeng Li
- Daryll Vanover
- Eric R. Lafontaine
- Gregory D Sempowski
- Hannah E. Peck
- Jackelyn Murray
- Jae Yeon Joo
- James E. Crowe, Jr.
- Kevin O Saunders
- Laura Rotolo
- Lorena C. S. Chaves
- Nathan Holladay
- Nichole Orr‐burks
- Philip J Santangelo
- Robert J Hogan
- Ryan A. Hobbs
- Younghun Jung
Organizations
- Defense Advanced Research Projects Agency
- Duke University
- Emory University
- Mississippi State University
- National Institutes of Health
- University of Georgia
- Vanderbilt University