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

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Key Lab of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China
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Laboratory Medicine Center, Pediatric Institute, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China
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Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Viruses 2015, 7(2), 798-819; https://doi.org/10.3390/v7020798
Received: 16 October 2014 / Revised: 5 February 2015 / Accepted: 10 February 2015 / Published: 16 February 2015
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. View Full-Text
Keywords: human serum albumin (HSA); pre-exposure prophylaxis (PrEP); respiratory syncytial virus (RSV); entry inhibitor; antiviral human serum albumin (HSA); pre-exposure prophylaxis (PrEP); respiratory syncytial virus (RSV); entry inhibitor; antiviral
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Sun, Z.; Wang, Q.; Jia, R.; Xia, S.; Li, Y.; Liu, Q.; Xu, W.; Xu, J.; Du, L.; Lu, L.; Jiang, S. Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection. Viruses 2015, 7, 798-819.

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