Nebulized inhaled mRNA-encoded membrane-localized antibodies for SARS-CoV-2 infection protection in hamsters

To date, 270 million people worldwide have been infected with SARS-CoV-2, and as of January 2022, COVID-19 has killed more than 5 million
people worldwide 。 Although there are already two mRNA-based vaccines, including an adenovirus vector vaccine and multiple monoclonal antibody (mAb) therapies, which have received emergency use authorization from the US Food and Drug Administration (FDA) or conditional marketing authorization from the European Medicines Agency in the European Union for prevention and treatment, shortcomings such as vaccine safety concerns, insufficient antigen inactivation, and the need to rely on professionals to use mAbs have led scientists to try to develop a convenient self-administered method to limit the spread of the virus
。 One of the main disadvantages of
using mAbs for passive immunization and treatment is due to the high cost of use due to factors such as the large dose required for mAb treatment (10-100 mg ^kg-1) and the need to administer it in hospitals.

Neutralizing mAbs through mRNA expression has the following advantages: (1) Unlike DNA and DNA-based viral vectors, mRNA does not normally enter the nucleus, thus reducing the risk of fusion with the
host genome.
And mRNA degradation is relatively fast, and long-term effects can be minimized; (2) The dose of mRNA required for direct delivery of the mAb to the desired site (respiratory tract) is much smaller (0.
1-1 mg ^kg-1)
compared to intravenous or intramuscular injection.

Advanced Science published the research article "Nebulized mRNA-Encoded Antibodies Protect Hamsters from SARS-CoV-2" by Professor Philip J.
Santangelo of Emory University and Professor Eric R.
Lafontaine and Professor Robert J.
Hogan of the University of Georgia in October 2022 Infection", the article developed a novel nebulized mRNA code to neutralize the mAb and validated it in a hamster infection model, confirming that the mAb can be effectively used in the prevention and treatment of SARS-CoV-2
.

The authors first verified the distribution of mRNA-encoded mAbs on cells and cell membranes, and confirmed that mAbs can effectively neutralize viruses
in vitro.
Furthermore, the expression distribution, effective concentration and half-life of mAb in hamsters were further studied by nebulized inhalation, and it was found that the expression distribution was in line with expectations, and the half-life was significantly prolonged, and it was found that the mAb did not cause obvious damage
to hamster lung tissue.
In addition to the treatment of pre-existing infections, the authors also studied the mAb's preventive effect on SARS-CoV-2 and found that it was effective in preventing hamsters from infection and improving body weight, viral titers, viral load, and inflammation of lung tissue
.
Overall, this study provides a new strategy
for the prevention and treatment of SARS-CoV-2 infection.

The first author of the article is Daryll Vanover, and the corresponding authors are Philip J.
Santangelo of Emory University and Eric R.
Lafontaine and Robert
J.
Hogan of the University of Georgia.

WILEY

Paper Information:

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.
, Hogan, R.
J.
, Santangelo, P.
J.

Nebulized mRNA-Encoded Antibodies Protect Hamsters from SARS-CoV-2 Infection.

Adv.
Sci.
 2022, 2202771.
 

Click "Read Original" in the lower left corner to view the original text
of the paper.

AdvancedScienceNews

Wiley's official WeChat platform for scientific research information

Long press the QR code to follow us

Share cutting-edge information | focus on scientific research trends

To publish research news or apply for information sharing, please contact: ASNChina@Wiley.
com