tetano
Editor, Senior Moderator
Adv Sci (Weinh)
. 2022 Oct 31;e2202771.
doi: 10.1002/advs.202202771. Online ahead of print.
Nebulized mRNA-Encoded Antibodies Protect Hamsters from SARS-CoV-2 Infection
Daryll Vanover[SUP] 1 [/SUP], Chiara Zurla[SUP] 1 [/SUP], Hannah E Peck[SUP] 1 [/SUP], Nichole Orr-Burks[SUP] 2 [/SUP], Jae Yeon Joo[SUP] 1 [/SUP], Jackelyn Murray[SUP] 2 [/SUP], Nathan Holladay[SUP] 2 [/SUP], Ryan A Hobbs[SUP] 1 [/SUP], Younghun Jung[SUP] 1 [/SUP], Lorena C S Chaves[SUP] 1 [/SUP], Laura Rotolo[SUP] 1 [/SUP], Aaron W Lifland[SUP] 1 [/SUP], Alicia K Olivier[SUP] 3 [/SUP], Dapeng Li[SUP] 4 [/SUP], Kevin O Saunders[SUP] 5 [/SUP], Gregory D Sempowski[SUP] 4 [/SUP], James E Crowe Jr[SUP] 6 [/SUP], Barton F Haynes[SUP] 4 [/SUP], Eric R Lafontaine[SUP] 2 [/SUP], Robert J Hogan[SUP] 2 7 [/SUP], Philip J Santangelo[SUP] 1 [/SUP]
Affiliations
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.
Keywords: RNA therapeutics; SARS-CoV-2; antibody therapies; gene therapies; passive immunizations.
. 2022 Oct 31;e2202771.
doi: 10.1002/advs.202202771. Online ahead of print.
Nebulized mRNA-Encoded Antibodies Protect Hamsters from SARS-CoV-2 Infection
Daryll Vanover[SUP] 1 [/SUP], Chiara Zurla[SUP] 1 [/SUP], Hannah E Peck[SUP] 1 [/SUP], Nichole Orr-Burks[SUP] 2 [/SUP], Jae Yeon Joo[SUP] 1 [/SUP], Jackelyn Murray[SUP] 2 [/SUP], Nathan Holladay[SUP] 2 [/SUP], Ryan A Hobbs[SUP] 1 [/SUP], Younghun Jung[SUP] 1 [/SUP], Lorena C S Chaves[SUP] 1 [/SUP], Laura Rotolo[SUP] 1 [/SUP], Aaron W Lifland[SUP] 1 [/SUP], Alicia K Olivier[SUP] 3 [/SUP], Dapeng Li[SUP] 4 [/SUP], Kevin O Saunders[SUP] 5 [/SUP], Gregory D Sempowski[SUP] 4 [/SUP], James E Crowe Jr[SUP] 6 [/SUP], Barton F Haynes[SUP] 4 [/SUP], Eric R Lafontaine[SUP] 2 [/SUP], Robert J Hogan[SUP] 2 7 [/SUP], Philip J Santangelo[SUP] 1 [/SUP]
Affiliations
- PMID: 36316224
- DOI: 10.1002/advs.202202771
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.
Keywords: RNA therapeutics; SARS-CoV-2; antibody therapies; gene therapies; passive immunizations.