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Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters.
Cell Rep Med. 2021 Mar 16; 2(3):100218.CR

Abstract

SARS-CoV-2 infection results in viral burden in the respiratory tract, enabling transmission and leading to substantial lung pathology. The 1212C2 fully human monoclonal antibody was derived from an IgM memory B cell of a COVID-19 patient, has high affinity for the Spike protein receptor binding domain, neutralizes SARS-CoV-2, and exhibits in vivo prophylactic and therapeutic activity in hamsters when delivered intraperitoneally, reducing upper and lower respiratory viral burden and lung pathology. Inhalation of nebulized 1212C2 at levels as low as 0.6 mg/kg, corresponding to 0.03 mg/kg lung-deposited dose, reduced the viral burden below the detection limit and mitigated lung pathology. The therapeutic efficacy of an exceedingly low dose of inhaled 1212C2 supports the rationale for local lung delivery for dose-sparing benefits, as compared to the conventional parenteral route of administration. These results suggest that the clinical development of 1212C2 formulated and delivered via inhalation for the treatment of SARS-CoV-2 infection should be considered.

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Publisher Full Text
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Authors+Show Affiliations

Piepenbrink MS
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Park JG
Texas Biomedical Research Institute, San Antonio, TX, USA.
Oladunni FS
Texas Biomedical Research Institute, San Antonio, TX, USA.
Deshpande A
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Basu M
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Sarkar S
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Loos A
Aridis Pharmaceuticals, San Jose, CA, USA.
Woo J
Aridis Pharmaceuticals, San Jose, CA, USA.
Lovalenti P
Aridis Pharmaceuticals, San Jose, CA, USA.
Sloan D
Aridis Pharmaceuticals, San Jose, CA, USA.
Ye C
Texas Biomedical Research Institute, San Antonio, TX, USA.
Chiem K
Texas Biomedical Research Institute, San Antonio, TX, USA.
Bates CW
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Burch RE
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Erdmann NB
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Goepfert PA
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Truong VL
Aridis Pharmaceuticals, San Jose, CA, USA.
Walter MR
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Martinez-Sobrido L
Texas Biomedical Research Institute, San Antonio, TX, USA.
Kobie JJ
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33649747

Citation

Piepenbrink, Michael S., et al. "Therapeutic Activity of an Inhaled Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody in Hamsters." Cell Reports. Medicine, vol. 2, no. 3, 2021, p. 100218.
Piepenbrink MS, Park JG, Oladunni FS, et al. Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters. Cell Rep Med. 2021;2(3):100218.
Piepenbrink, M. S., Park, J. G., Oladunni, F. S., Deshpande, A., Basu, M., Sarkar, S., Loos, A., Woo, J., Lovalenti, P., Sloan, D., Ye, C., Chiem, K., Bates, C. W., Burch, R. E., Erdmann, N. B., Goepfert, P. A., Truong, V. L., Walter, M. R., Martinez-Sobrido, L., & Kobie, J. J. (2021). Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters. Cell Reports. Medicine, 2(3), 100218. https://doi.org/10.1016/j.xcrm.2021.100218
Piepenbrink MS, et al. Therapeutic Activity of an Inhaled Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody in Hamsters. Cell Rep Med. 2021 Mar 16;2(3):100218. PubMed PMID: 33649747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters. AU - Piepenbrink,Michael S, AU - Park,Jun-Gyu, AU - Oladunni,Fatai S, AU - Deshpande,Ashlesha, AU - Basu,Madhubanti, AU - Sarkar,Sanghita, AU - Loos,Andreas, AU - Woo,Jennifer, AU - Lovalenti,Phillip, AU - Sloan,Derek, AU - Ye,Chengjin, AU - Chiem,Kevin, AU - Bates,Christopher W, AU - Burch,Reuben E, AU - Erdmann,Nathaniel B, AU - Goepfert,Paul A, AU - Truong,Vu L, AU - Walter,Mark R, AU - Martinez-Sobrido,Luis, AU - Kobie,James J, Y1 - 2021/02/25/ PY - 2020/11/18/received PY - 2020/12/23/revised PY - 2021/02/17/accepted PY - 2021/3/3/pubmed PY - 2021/3/3/medline PY - 2021/3/2/entrez KW - B cell KW - COVID-19 KW - IgM KW - RBD KW - SARS-CoV-2 KW - Spike KW - hamsters KW - inhalation KW - monoclonal antibody KW - neutralizing SP - 100218 EP - 100218 JF - Cell reports. Medicine JO - Cell Rep Med VL - 2 IS - 3 N2 - SARS-CoV-2 infection results in viral burden in the respiratory tract, enabling transmission and leading to substantial lung pathology. The 1212C2 fully human monoclonal antibody was derived from an IgM memory B cell of a COVID-19 patient, has high affinity for the Spike protein receptor binding domain, neutralizes SARS-CoV-2, and exhibits in vivo prophylactic and therapeutic activity in hamsters when delivered intraperitoneally, reducing upper and lower respiratory viral burden and lung pathology. Inhalation of nebulized 1212C2 at levels as low as 0.6 mg/kg, corresponding to 0.03 mg/kg lung-deposited dose, reduced the viral burden below the detection limit and mitigated lung pathology. The therapeutic efficacy of an exceedingly low dose of inhaled 1212C2 supports the rationale for local lung delivery for dose-sparing benefits, as compared to the conventional parenteral route of administration. These results suggest that the clinical development of 1212C2 formulated and delivered via inhalation for the treatment of SARS-CoV-2 infection should be considered. SN - 2666-3791 UR - https://www.unboundmedicine.com/medline/citation/33649747/Therapeutic_activity_of_an_inhaled_potent_SARS-CoV-2_neutralizing_human_monoclonal_antibody_in_hamsters. L2 - https://linkinghub.elsevier.com/retrieve/pii/S2666-3791(21)00034-3 DB - PRIME DP - Unbound Medicine ER -
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