Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection

Viruses

Zhiwu Sun²  Qian Wang²  Ran Jia¹  Shuai Xia²  Yuan Li²  Qi Liu²  Wei Xu²  Jin Xu¹  Lanying Du³  Lu Lu²  Shibo Jiang² 

[1] Laboratory Medicine Center, Pediatric Institute, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China; E-Mails:;Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China; E-Mails:;Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA; E-Mail:

关键词: human serum albumin (HSA);    pre-exposure prophylaxis (PrEP);    respiratory syncytial virus (RSV);    entry inhibitor;    antiviral;   

DOI  :  10.3390/v7020798

来源: mdpi

【 摘 要 】

Respiratory syncytial virus (RSV) is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP) of RSV infection in children at high risk. We found that maleic anhydride (ML)-modified human serum albumin (HSA), designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.