2. Academic Validation
  3. Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2

Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2

  • Front Immunol. 2022 Sep 14;13:980435. doi: 10.3389/fimmu.2022.980435.
Yun Ji 1,  Qi Zhang 2,  Lin Cheng 3,  Jiwan Ge 4,  Ruoke Wang 2,  Mengqi Fang 2,  Eric M Mucker 5,  Peng Chen 2,  Ji Ma 1,  Rui Zhang 2,  Chunming Li 6,  Holly Hammond 7,  Lauren Baracco 7,  Michael Holbrook 8,  Matthew Frieman 7,  Zheng Zhang 3,  Xinquan Wang 4,  Jay W Hooper 5,  Linqi Zhang 2,  Qing Zhu 1
Affiliations

Affiliations

  • 1 Brii Biosciences Inc., Durham, NC, United States.
  • 2 Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
  • 3 Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.
  • 4 The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China.
  • 5 U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, United States.
  • 6 Brii Biosciences Inc., Beijing, China.
  • 7 Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States.
  • 8 Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases (NIAID), Fort Detrick, MD, United States.
PMID: 36189212 DOI: 10.3389/fimmu.2022.980435
Abstract

Monoclonal Antibodies (mAbs) targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have demonstrated clinical efficacy in preventing or treating coronavirus disease 2019 (COVID-19), resulting in the emergency use authorization (EUA) for several SARS-CoV-2 targeting mAb by regulatory authority. However, the continuous virus evolution requires diverse mAb options to combat variants. Here we describe two fully human mAbs, amubarvimab (BRII-196) and romlusevimab (BRII-198) that bind to non-competing epitopes on the receptor binding domain (RBD) of spike protein and effectively neutralize SARS-CoV-2 variants. A YTE modification was introduced to the fragment crystallizable (Fc) region of both mAbs to prolong serum half-life and reduce effector function. The amubarvimab and romlusevimab combination retained activity against most mutations associated with reduced susceptibility to previously authorized mAbs and against variants containing amino acid substitutions in their epitope regions. Consistently, the combination of amubarvimab and romlusevimab effectively neutralized a wide range of viruses including most variants of concern and interest in vitro. In a Syrian golden hamster model of SARS-CoV-2 Infection, Animals receiving combination of amubarvimab and romlusevimab either pre- or post-infection demonstrated less weight loss, significantly decreased viral load in the lungs, and reduced lung pathology compared to controls. These preclinical findings support their development as an antibody cocktail therapeutic option against COVID-19 in the clinic.

Keywords

M252Y/S254T/T256E (YTE); amubarvimab (BRII-196); half-maximal inhibitory concentration (IC50); monoclonal antibody (mAb); receptor binding domain (RBD); romlusevimab (BRII-198); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); variant of concern (VOC).

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