Induction of Sterilizing Immunity against West Nile Virus (WNV), by Immunization with WNV‐Like Particles Produced in Insect Cells

Abstract

No specific vaccine for West Nile virus (WNV) is currently available for human use. In the present study, we describe the generation of WNV-like particles (WNV-LPs) in insect cells by use of recombinant baculoviruses expressing the WNV structural proteins prME or CprME. BALB/c mice immunized with purified WNV-LPs developed WNV-specific antibodies that had potent neutralizing activities. Mice immunized with prME-like particles (prME-LPs) showed no morbidity or mortality after challenge with WNV. Immunization with prME-LPs can induce sterilizing immunity without producing any evidence of viremia or viral RNA in the spleen or brain. These results suggest that WNV-LPs hold promise as a vaccine candidate for WNV infection.

Monoclonal Antibody-Based Competitive Enzyme-Linked Immunosorbent Assay for Detecting and Quantifying West Nile Virus-Neutralizing Antibodies in Horse Sera

“…Neutralizing antibodies induced by domain III of flaviviral E proteins have been reported elsewhere as a major factor responsible for the greatest protection in vivo (24,29), and all types of recently developed bioengineered vaccines target the E protein (1,9,10,12,15,20,27,28,33,35). In our assay, competition for binding of MAb 5E8 by serum antibodies was observed in most of the serum samples from vaccinated horses (96.1%) as well as in serum samples from early infected mice.…”

“…Therefore, in order to replace the whole-virus antigen in the NT-ELISA, we are investigating the efficacy of recombinant proteins with correct antigenic structures, generated using native whole-virus particles such as recombinant virus-like particles (14,25,28).…”

“…Various types of vaccines for WNV have been explored for their ability to protect susceptible hosts against pathogenic WNV infection: formalin-inactivated (18,22), live attenuated (37), and recombinant chimeric virus vaccines (1,10,15,20,27); recombinant PrM/E or E protein vaccines (28,34); and DNA-based vaccines (9,12,33). Currently, a formalin-inactivated WNV vaccine (West Nile-Innovator; Fort Dodge Animal Health, IA) and a recombinant canarypox virus vector-based vaccine expressing PrM/E proteins of WNV (Recombitek; Merial Limited, GA) are commercially available for veterinary use in the United States (23).…”

Production of Pseudoinfectious Yellow Fever Virus with a Two-Component Genome

“…These so-called subviral particles (SVPs) contain no RNA or capsid protein (29), but have the envelope proteins organized into an icosahedral, lipid-containing structure (41). The prM/ E-embedded SVPs are capable of inducing an efficient immune response that protects animals against a future infection with the replication-competent viruses (17,18,20,37). These SVPs can be produced from viral or DNA vectors.…”

Evaluation of Extracellular Subviral Particles of Dengue Virus Type 2 and Japanese Encephalitis Virus Produced bySpodoptera frugiperdaCells for Use as Vaccine and Diagnostic Antigens

“…Other laboratories have established high-yield expression systems for EPs of JEV or West Nile virus using the mammalian cell lines COS-1 (5, 15), RK-13 (24,43), and CHO-K1 (52). In addition to mammalian cells, bacterial (2,42,54,57), yeast (7,8,38), and insect (23,36,48,51,56) cells have been used to produce flavivirus vaccine candidates; most of these studies have focused on a truncated E protein or domain III of the E protein. These vaccine candidates were able to induce neutralizing antibodies and/or protection in animals.…”