Development and characterization of neutralizing monoclonal antibodies against clinically relevant human adenovirus subgroup B serotypes

Yuelin Wang; Wei Dou; Yingying Chen; Ke Liu; Mengjun Li; Tyuji Hoshino; Yushan Jiang; Vladislav Victorovich Khrustalev; Alexey V. Churov; Alexander N. Orekhov; Wei Zhao; Ling Li; Yang Yang; Chenguang Shen

doi:10.1016/j.virs.2026.03.017

April 2026

Citation: Yuelin Wang, Wei Dou, Yingying Chen, Ke Liu, Mengjun Li, Tyuji Hoshino, Yushan Jiang, Vladislav Victorovich Khrustalev, Alexey V. Churov, Alexander N. Orekhov, Wei Zhao, Ling Li, Yang Yang, Chenguang Shen. Development and characterization of neutralizing monoclonal antibodies against clinically relevant human adenovirus subgroup B serotypes .VIROLOGICA SINICA, 2026, 41(2) : 404-412. http://dx.doi.org/10.1016/j.virs.2026.03.017

Development and characterization of neutralizing monoclonal antibodies against clinically relevant human adenovirus subgroup B serotypes

Yuelin Wang ^a,b ,
Wei Dou ^a ,
Yingying Chen ^a,c ,
Ke Liu ^a ,
Mengjun Li ^a ,
Tyuji Hoshino ^d ,
Yushan Jiang ^a ,
Vladislav Victorovich Khrustalev ^e ,
Alexey V. Churov ^f ,
Alexander N. Orekhov ^f ,
Wei Zhao ^{a
,,} ,
Ling Li ^{a,c
,,} ,
Yang Yang ^{b
,,} ,
Chenguang Shen ^{a,g,h
,,}

a. BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China;
b. National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China;
c. School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China;
d. Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan;
e. Department of General Chemistry, Belarusian State Medical University, Minsk 220045, Belarus;
f. Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia;
g. Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China;
h. Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou 510515, China

Corresponding author: Wei Zhao, zhaowei@smu.edu.cn
Ling Li, liling@smu.edu.cn
Yang Yang, young@mail.sustech.edu.cn
Chenguang Shen, a124965468@smu.edu.cn
Available online: 02 April 2026

Abstract

Human adenoviruses (HAdVs), particularly subgroup B serotypes HAdV-3 and HAdV-55, are associated with severe respiratory disease and currently lack targeted therapies. While neutralizing monoclonal antibodies (nMAbs) offer promising therapeutic potential, the specific nMAbs targeting these serotypes remain poorly characterized. Therefore, this study aimed to generate and evaluate the efficacy of serotype-specific nMAbs against HAdV-3 and HAdV-55. Mice were immunized with HAdV-3 virions, HAdV-55 virions, or recombinant fiber knob proteins (HAdV-55/-7) for the generation of serotype-specific nMAbs, and their efficacy was systematically evaluated using in vitro assays and an in vivo tree shrew model. Through comprehensive screening, eleven MAbs were identified with specificity against HAdV-3 (six clones) or HAdV-55/-7 fiber knob (five clones). Four nMAbs exhibited potent neutralizing activity: 13F12 (half-maximal inhibitory concentration, IC₅₀: 3.8 μg/mL), 8D2 (IC₅₀: 15.1 μg/mL), 3A3 (IC₅₀: 14.9 μg/mL) against HAdV-3 virions, and 8F2 with neutralizing efficacy against HAdV-55 virions (IC₅₀: 30.4 μg/mL). Western blot analysis revealed that MAbs 13F12 and 8F2 targeted the fiber protein, whereas 8D2 and 3A3 bound to the hexon protein. Furthermore, in vivo evaluations demonstrated that 13F12 significantly reduced viral loads in nasal turbinates and attenuated lung pathology in HAdV-3-infected tree shrews. Mechanistically, all tested anti-HAdV-3 nMAbs inhibited infection by blocking viral attachment (P < 0.01 vs. controls). In conclusion, this study underscores the therapeutic potential of targeting viral entry and highlights 13F12 as a promising candidate for HAdV prophylaxis.
- Human adenovirus (HAdV)
- , Neutralizing antibody
- , Monoclonal antibody
- , Antiviral therapy
- , Respiratory infection
- , B subgroup serotypes

Electronic Supplementary Material

10.1016j.virs.2026.03.017-ESM.docx
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