To the Editor
The ACTIV-3/TICO LY-CoV555 Examine Group (Dec. 22)1 hypothesized that low penetration of the antibody into the contaminated lungs may clarify the shortage of advantage of bamlanivimab (LY-CoV555) in hospitalized sufferers with coronavirus illness 2019 (Covid-19). Nonetheless, we beforehand measured transudation of human immunodeficiency virus sort 1 (HIV-1) monoclonal antibodies (VRC07-523 and PGT121) into tissues of 1-month-old rhesus macaques as a part of a research to evaluate the effectiveness of monoclonal antibodies as postexposure prophylaxis.2 We detected excessive concentrations of passively transferred antibodies within the lungs of the 2 macaques (250 ng per milliliter in a single and 285 ng per milliliter within the different) after subcutaneous administration of 10 mg per kilogram of physique weight of monoclonal antibody cocktail. The focus of antibody within the lungs was greater than the imply focus detected in 26 different tissues (184 ng per milliliter); monoclonal antibody biodistribution was not affected by the virus in challenged animals.
Our observations counsel that the fast number of neutralization-resistant variants, fairly than biodistribution, may need undermined the efficacy of bamlanivimab on this trial. This speculation is supported by current information offered by Regeneron concerning the preliminary efficacy of the mixture of casirivimab and imdevimab in decreasing the danger of demise or mechanical air flow in hospitalized sufferers with Covid-19.3
Juan P. Jaworski, D.V.M., Ph.D.
Consejo Nacional de Investigaciones CientÃficas y Técnicas, Buenos Aires, Argentina
[email protected]
No potential battle of curiosity related to this letter was reported.
This letter was printed on February 3, 2021, at NEJM.org.
Response
Jens D. Lundgren, M.D.
Rigshospitalet, Copenhagen, Denmark
[email protected]
H. Clifford Lane, M.D.
Nationwide Institute of Allergy and Infectious Ailments, Bethesda, MD
James D. Neaton, Ph.D.
College of Minnesota, Minnesota, MN
Since publication of their article, the authors report no additional potential battle of curiosity.
This letter was printed on February 3, 2021, at NEJM.org.
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1. Tabrizi M, Bornstein GG, Suria H. Biodistribution mechanisms of therapeutic monoclonal antibodies in well being and illness. AAPS J 2010;12:33–43.
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2. Hart TK, Cook dinner RM, Zia-Amirhosseini P, et al. Preclinical efficacy and security of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys. J Allergy Clin Immunol 2001;108:250–257.
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3. Regeneron Prescribed drugs. Regeneron pronounces encouraging preliminary information from COVID-19 antibody cocktail trial in hospitalized sufferers on low-flow oxygen. December 29, 2020 (https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-encouraging-initial-data-covid-19-antibody).
