Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Recombinant virus encoding one or more heterologous proteins...
Reexamination Certificate
1999-06-16
2001-11-27
Mosher, Mary E. (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Recombinant virus encoding one or more heterologous proteins...
C424S205100, C424S229100, C424S817000, C435S235100, C435S236000, C435S320100
Reexamination Certificate
active
06322793
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention of this application pertains to a vaccine for channel catfish virus, and in particular, a recombinant vaccine with gene 50 of the wild type or V60 channel catfish virus deleted or substantially deleted from the channel catfish virus. This invention also pertains to methods of vaccinating channel catfish against channel catfish virus, using the gene 50-deleted recombinant virus.
2. Background of the Prior Art
Channel catfish virus (CCV) (Ictalurid herpesvirus-1) is a cytopathic herpesvirus that can cause an acute, hemorrhagic, and lethal disease in the channel catfish Ictalurus punctatus (Fijan, 1968). Acute CCV epizootics in populations of fry and fingerling channel catfish can result in mortalities as high as 95% within one week (Plumb, 1978).
To date, three kinds of vaccines against CCV have been described in the literature. The first used a classically attenuated strain of the CCV Auburn strain (strain V60, Hartmann and Noga, 1980; Noga and Hartmann, 1981); the second was a subunit vaccine based on a preparation of viral envelope proteins (Awad et al. 1987); the third uses a live, thymidine-kinase-negative recombinant (Zhang and Hanson, 1995).
Considering the increasing importance of the channel catfish as a food source, the desirability of obtaining a vaccine for CCV to prevent the economic loss in hatcheries is evident. We studied the attenuated V60 strain, produced by multiple passages in cultured alternate host cells. The strain provides a protective vaccine strain against wild-type virus. When administered parenterally or as a water-borne vaccine, the strain was found to protect catfish fingerlings against a viral challenge, promoting a survival rate of over 90% (Walczak et al., 1981). A major deletion was found in gene 50 of the V60 strain (Vanderhejiden et al, 1996). Gene 50 encodes a secreted glycoprotein, highly glycosylated like the mucin-type glycoproteins, designated gp 250 (Vanderheijden, et al., 1999). Few viral glycoproteins are secreted upon herpesvirus infection (Randall et al 1980) and their function in the viral cycle by is still unclear. Since the attenuated V60 strain possesses a large deletion in its gene 50, the possibility exists that this gene could be responsible, at least in part, for the virulence of the wild-type strain. This possibility, therefore, offers a potential vaccine development route.
SUMMARY OF THE INVENTION
This invention includes, in its broadest embodiment, a recombinant channel catfish virus, with all or substantially all of gene 50 deleted. By substantially all is intended to include sufficient deletions so as to prevent, partially or totally the expression of the native secreted glycoprotein encoded by gene 50 of CCV. Within the invention, portions of either or both the 5′ or 3′ terminus of gene 50 may be retained, while retaining the attenuated characteristic of the inventive recombinant vaccine. Provided sufficient deletion has occurred to prevent expression of the glycoprotein, virulence of infection with the attenuated vaccine will be avoided, and the goal of the invention achieved.
In its broadest embodiment, the ORF for gene
50
is simply not present. It may be deleted entirely, or replaced with an avirulent sequence. In the invention described herein below, gene
50
was replaced with a detectable reporter gene, lacZ. Other reporter genes may be inserted in place of gene
50
, or nuclear material encoding an innocuous protein may be included, provided it does not interfere with expression of the recombinant virus such that challenge protection is achieved by sufficiently high circulating antibody titer. Selection of appropriate inserts, or simple deletion of the gene
50
without replacement with other nuclear material, is within the scope of those of skill in the art given the disclosure herein below, and remains part of the invention.
REFERENCES:
patent: 4219543 (1980-08-01), Hartmann et al.
patent: 5223424 (1993-06-01), Cochran et al.
Vanderheijden et al. Virology 218: 422-426, Apr. 1996.*
Zhang et al. Journal of Fish Diseases 19:121-128, 1996.*
Kancharla et al. Diseases of Aquatic Organisms 37:25-34, 1996.*
Zhang et al. Virology 209:658-663, 1995.*
The Audobon Society Nature Guides: Wetlands. 1985. W.A. Niering et al. Alfred A. Knopf, Inc., New York. p. 376.
Hanson Larry A.
Martial Joseph A.
Vanderheijden Nathalie
Kelber Steven B.
Mississippi State University
Mosher Mary E.
Piper Marbury Rudnick & Wolfe LLP
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