Immunogenicity and efficacy of two types of West Nile virus-like particles different in size and maturation as a second-generation vaccine candidate.
Virus-like particles (VLPs) of flaviviruses generated from the prM and E genes are a promising vaccine candidate. We have established cell clones continuously releasing VLPs of West Nile virus (WNV) in serum-free conditions. Two types of VLPs were distinguished by sedimenting analyses in sucrose density gradients. Fast sedimenting VLPs (F-VLPs) were large (40-50 nm) and composed of the E and processed mature M proteins, whereas slowly sedimenting VLPs (S-VLPs) were small (20-30 nm) particles consisting of the E and immature prM proteins. F-VLPs induced higher neutralizing antibody and anti-WNV IgG titers than S-VLPs. Furthermore, IgG2a was dominant over IgG1 by immunization with F-VLPs as with whole virion-derived antigens. Mice vaccinated with a low dose (3 ng) of F-VLPs showed higher protective efficacy (83% survivals) against WNV infection than S-VLP-immune mice (17% survivals). These results indicate that F-VLPs more closely resemble the virions and take a better immunogenic form than S-VLPs as WNV vaccine candidates.
Ohtaki
Naohiro
N
Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
Takahashi
Hidehiro
H
Kaneko
Keiko
K
Gomi
Yasuyuki
Y
Ishikawa
Toyokazu
T
Higashi
Yasushi
Y
Kurata
Takeshi
T
Sata
Tetsutaro
T
Kojima
Asato
A
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D016466:CHO Cells; D002499:Centrifugation, Density Gradient; D006224:Cricetinae; D003412:Cricetulus; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D010316:Particle Size; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D058425:Vaccines, Virus-Like Particle; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D053060:West Nile Virus Vaccines