Nebulized mRNA-encoded antibodies protect hamsters from SARS-CoV-2 infection
Vanover, D., Zurla, C., Peck, H. E., Orr-Burks, N., Joo, J. Y., Murray, J., Holladay, N., Hobbs, R. A., Jung, Y., Chaves, L. C. S., Rotolo, L., Lifland, A. W., Olivier, A. K., Li, D., Saunders, K. O., Sempowski, G. D., Crowe, J. E., Haynes, B. F., Lafontaine, E. R., ... Santangelo, P. J. (2022). Nebulized mRNA-encoded antibodies protect hamsters from SARS-CoV-2 infection. Advanced Science, 9(34), Article e2202771. https://doi.org/10.1002/advs.202202771
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.