Potent monoclonal antibodies against multidrug-resistant hypervirulent Klebsiella pneumoniae

Yushan Jiang; Zhuolin Li; Yang Yang; Zihan He; Tyuji Hoshino; Vladislav Victorovich Khrustalev; Qing Zhu; Weiling Wu; Wei Zhao; Chenguang Shen; Shi Ouyang

doi:10.1002/inmd.70115

Interdisciplinary Medicine ›› 2026, Vol. 4 ›› Issue (4) :e70115 DOI: 10.1002/inmd.70115

RESEARCH ARTICLE

Potent monoclonal antibodies against multidrug-resistant hypervirulent Klebsiella pneumoniae

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¹. Department of Infectious Diseases, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

². BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China

³. Department of Laboratory Medicine, Baiyun District People's Hospital of Guangzhou, Guangzhou, China

⁴. National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China

⁵. Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan

⁶. Department of General Chemistry, Belarusian State Medical University, Minsk, Belarus

⁷. Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

⁸. Department of Laboratory Medicine, Zhujiang Hospital, Key Laboratory of Infectious Diseases Research in South China, Southern Medical University, Ministry of Education, Guangzhou, China

yushan.y.jiang@gmail.com

zhaowei@smu.edu.cn

a124965468@smu.edu.cn

ouyangshi@gzhmu.edu.cn

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Abstract

Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) infections present a therapeutic challenge owing to profound antibiotic resistance and the paucity of cross-serotype protective strategies against distinct serovars (e.g., K1/K2). Mice were subcutaneously immunized with the viable, hypovirulent, multidrug-resistant (MDR) strain Kp00198874 (serotype K64). Cross-reactive monoclonal antibodies (mAbs) were derived using hybridoma technology. Immunization elicited cross-serotype protective antibodies, ensuring 100% survival rates against lethal challenges posed by the K1/K2 serotype strains. In contrast to single neutralizing antibodies, mAbs 2D4 and 2E10 modulate phagocytic bacteria and immune responses. Prophylactic administration of mAbs conferred 100% survival rates against Kp-GZ8 and significantly prolonged the median survival time against ATCC43816 cells. Therapeutic intervention with mAbs mitigated post-infection pulmonary hemorrhage and inflammatory responses. mAbs 2D4 and 2E10 synergistically targeted capsular polysaccharide/protein epitopes to achieve cross-serotype-protective efficacy. This study established live Kp00198874 immunization as a novel platform for generating cross-protective mAbs against lethal MDR-hvKP, with 2D4 and 2E10 providing complementary mechanisms (rapid pathogen clearance and immunomodulation) through conserved epitope targeting, offering an antibody-based alternative for resistant infections.

Keywords

hypervirulence / Klebsiella pneumoniae / monoclonal antibodies / multidrug resistance / neutralizing antibodies

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Yushan Jiang, Zhuolin Li, Yang Yang, Zihan He, Tyuji Hoshino, Vladislav Victorovich Khrustalev, Qing Zhu, Weiling Wu, Wei Zhao, Chenguang Shen, Shi Ouyang. Potent monoclonal antibodies against multidrug-resistant hypervirulent Klebsiella pneumoniae. Interdisciplinary Medicine, 2026, 4 (4) : e70115 DOI:10.1002/inmd.70115

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