Abstract
West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′)2 fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab′)2 fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab′)2 passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.
Highlights
In recent years, the incidences of West Nile virus (WNV) infection from Culex to humans have increased greatly due to global travel, which raises the public health concern that the 1999–2002 WNV pandemic in North America could recur [1,2]
Prophylactic and therapeutic treatment of mice with purified IgG or F(ab0 )[2] fragments significantly decreased the viral loads in the spleens and brains of WNV-infected mice, and reduced mortality. These results indicate that equine immunoglobulin and equine neutralizing F(ab0 )[2] passive immunotherapy could be potentially useful for the treatment of patients infected with WNV
The virus-like particles (VLP) pellets were resuspended in phosphate-buffered saline (PBS) and loaded on a 10%–30%–50% discontinuous sucrose gradient
Summary
The incidences of West Nile virus (WNV) infection from Culex to humans have increased greatly due to global travel, which raises the public health concern that the 1999–2002 WNV pandemic in North America could recur [1,2]. The use of a large dose of ribavirin inhibited WNV replication in vitro [7]; it was less efficient in vivo—the mortality of the hamsters infected with WNV increased after the ribavirin injection [8]. The WNV RNA replication process is inhibited in vitro by mycophenolate (another candidate inhibitor) [9], which showed no protective effect in vivo. Another clinical study indicated that interferon alpha (IFN-α) could be protective against WNV infection [10]; only limited evidence has shown that IFN-α could cure patients with serious WNV encephalitis
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