Induction of a Protective Immune Response against Viral Nervous Necrosis in the European Sea Bass Dicentrarchus labrax by Using Betanodavirus Virus-Like Particles

Abstract

Betanodaviruses are causative agents of viral nervous necrosis (VNN), a devastating disease of cultured marine fish worldwide. Virus particles contain a single type of coat protein that spontaneously assembles into virus-like particles (VLPs) when expressed in a baculovirus expression system. In the present study, the immunogenicity of betanodavirus VLPs and the protection they confer against VNN in the European sea bass Dicentrarchus labrax were investigated. Enzyme-linked immunosorbent assay and seroneutralization tests performed on plasma from fish vaccinated intramuscularly with doses as low as 0.1 g of VLPs indicated that the VLPs elicited the synthesis of specific antibetanodavirus antibodies with neutralizing activity. Moreover, fish vaccinated with VLPs were protected from challenge with live virus. Both the immune response and the protective effect against viral challenge were dose dependent. Reverse transcription-PCR data indicated that higher doses of vaccine also reduced the number of fish containing detectable quantities of betanodavirus RNA on day 30 after challenge. Taken together these data strongly support the hypothesis that VLPs obtained in the baculovirus expression system may represent an effective vaccine against VNN.

Betanodavirus of Marine and Freshwater Fish: Distribution, Genomic Organization, Diagnosis and Control Measures

“…The open reading frame (ORF) contains a 982-amino-acid with a calculated molecular mass of 110.74 kDa. On the other hand, the smaller segment, RNA2 (1433 nt) having a G?C content of 53.24 % contains a 338-amino-acid major ORF which encodes the coat protein with a calculated molecular mass of 37.059 kDa flanked by 26 nt 5 0 -NTR and a 390 nt 3 0 -NTR [19,75,107,118]. RNA2 forms a major ORF of capsid protein and consists of a highly conserved region and a variable region.…”

“…To ensure that the fish are as healthy as possible, a useful and practical approach would be vaccination of fish and boosting their immune system. Various types of vaccines have been developed such as formalininactivated vaccine, subunit vaccine with recombinant coat protein of betanodavirus and nodavirus-like particle vaccine [58,74,111,116,118,121,124]. Vaccination trials have shown protection efficacy against betanodavirus infection.…”

Fish immunization using a synthetic double-stranded RNA Poly(I:C), an interferon inducer, offers protection against RGNNV, a fish nodavirus

“…Under these circumstances, several kinds of fish nodavirus vaccines have been developed, such as formalin-inactivated vaccine, subunit vaccine with a recombinant coat protein, virus-like particle vaccine, etc. (Húsgar7 et al 2001, Tanaka et al 2001, Yuasa et al 2002, Sommerset et al 2005, Yamashita et al 2005, Liu et al 2006, Thiéry et al 2006.…”

A Virus-Like Particle That Elicits Cross-Reactive Antibodies to the Conserved Stem of Influenza Virus Hemagglutinin

“…We and others have shown that icosahedral, virus-like particles (VLPs) represent highly effective platforms for the development of novel vaccines (4,19,21,24,30,31,38). Icosahedral virus particles are known to be strongly immunogenic based on the repetitive array of their component proteins, particulate nature, and ability to appropriately stimulate the innate immune response.…”