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Viral nucleotide sequences

a nucleotide sequence and virus technology, applied in the field of virus nucleotide sequences, can solve the problems of retained pathogenicity, infectious laryngotracheitis is also a worldwide problem,

Inactive Publication Date: 2001-09-27
MERIAL SAS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0044] The vectors in accordance with the invention may provide multivalent vaccine protection. For example, a vaccine comprising ILTV carrying an MDV antigen coding sequence would be expected to protect against ILT and Marek's Disease.
[0051] Thus, the construction of deletional or insertional mutants of ILTV can yield improved vaccines. Alternatively, the expression of ILTV glycoproteins or other ILTV proteins engineered into HVT, fowl pox or other vectors can constitute effective vaccines.

Problems solved by technology

Although the degree of protection can be improved by using a mixture of HVT, type 2 MDV and attenuated derivatives of very virulent strains for vaccination, the results have been erratic.
Infectious laryngotracheitis is also a worldwide problem.
However, it has retained some degree of pathogenicity.

Method used

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  • Viral nucleotide sequences
  • Viral nucleotide sequences
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Examples

Experimental program
Comparison scheme
Effect test

example 1

gB Gene of MDV

[0095] An M13 clone of HVT homologous to the gB gene of VZV and HSV hybridized to BamH1 fragment I3 of MDV (see FIG. 1). Sequencing of this fragment obtained from a BamH1 library of the RB1B strain of MDV showed that two thirds of the gene, starting with the NH.sub.2 terminus, was contained within I3. The remainder of the gene was identified in the adjacent restriction fragment K3. FIG. 1 shows the map position of the gene which is 2.6 Kbp long. Its mRNA has been estimated to be approximately 2.8 Kb. The translated protein is 865 amino acids long (FIG. 2). This includes approximately 20 amino acids which may be part of a signal sequence domain. The primary translated sequence of MDV gB has a few features in common with gB of other herpes viruses such as the alignment of cysteine residues and the presence of hydrophobic sequences which are presumably capable of spanning a lipid bilayer [Pellet, P. E. et al (1985), J. Virol. 53, 243-253]. However, MDV gB has only 48% ami...

example 2

gH Gene of HVT and gH Gene of MDV

[0096] An M13 clone of HVT containing sequences homologous to HSV gH was isolated during our earlier work on gene identification and mapping (Buckmaster et al (1988) as above). This clone, when used as a probe, hybridized to a 6 Kbp HindIII fragment of HVT (FIG. 3). Sequencing revealed that this fragment contained approximately one quarter of the gH gene including the carboxy terminus. The adjacent HindIII fragment (3.2 Kbp) containing the remainder of the gH gene was identified by hybridization using a cloned HpaI fragment of HVT which overlapped the HindIII site. FIG. 4 shows the sequence of the coding region of the gH gene of HVT (2.3 Kbp) and flanking sequences. The % amino acid identity between the gH gene of HVT and its homologue in HSV1, VZV and EBV was only 20, 24 and 20 respectively (estimated from maximised amino acid overlaps of 630, 644 and 153 respectively).

example 3

TK Gene of HVT and TK Gene of MDV

[0097] The whole coding region of the TK gene of HVT (1053 bp) was contained within the 3.2 Kbp HindIII fragment described above (FIG. 3). The sequence of the entire gene and flanking regions is shown in FIG. 5. Similarly the whole of the MDV TK gene is contained within the 3.6 Kbp BamH1 K2 fragment of MDV (FIG. 1). The sequence of MDV TK gene determined so far is shown in FIG. 5. Comparison of the MDV and HVT TK sequences indicates that the two genes have approximately 60% amino acid identity (estimated from 276 amino acid overlap). By contrast, the % amino acid identities between the TK gene of HVT and the TK genes of HSV 1, VZV and EBV are only 30, 27 and 24 respectively (estimated from amino acid overlaps of 320, 332 and 193 respectively). The predicted amino acid sequences of HVT and MDV TK show characteristic ATP and / or CTP binding site motifs described for a number of virus and eukaryotic proteins that are associated with phosphorylation (Gent...

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Abstract

Various genes of herpes virus of turkeys (HVT), Marek's disease virus (MDV) and infectious laryngotracheitis virus (ILTV) have been identified as non-essential regions (and candidates for insertion sites for foreign genes) and / or as antigen-encoding regions. The former include the HVT homologue of the HSV (herpes simplex virus) gC gene, the TK (thymidine kinase) region of MDV or ILTV, ORF3 of ILTV (as defined herein), the ribonucleotide reductase (large subunit) gene of ILTV, MDV or HVT and the ribonucleotide reductase (small subunit) gene of MDV. The antigen-encoding regions include the HVT homologues of the HSV gB, gC and gH genes, the ILTV homologue of HSV gB, ORF2 of ILTV, and the HVT homologue of the HSV-1 immediate early genes IE-175 and IE-68. Manipulation of these genes allows vaccines to be prepared comprising attenuated virus or virus carrying heterologous antigen-encoding sequences.

Description

[0001] The present invention relates to viral nucleotide sequences which may be manipulated to provide vaccines against disease.BACKGROUND AND DESCRIPTION OF PRIOR ART[0002] Herpesviruses are large double stranded DNA viruses consisting of an icosahedral capsid surrounded by an envelope. The group has been classified as alpha, beta and gammaherpesviruses on the basis of genome structure and biological properties [Roizman, B et al (1981) Inter-virology 16, 201-217]. Avian herpes viruses include Marek's Disease Virus (MDV) (a gammaherpesvirus) which causes a lymphomatous disease of considerable economic importance in chickens [reviewed in Payne, L. N. (ed) Marek's Disease (1985), Martinus Nijhoff Publishing, Boston] and Infectious Laryngotracheitis Virus (ILTV) (an alphaherpesvirus) which causes an acute upper respiratory tract infection in chickens resulting in mortality and loss of egg production.[0003] A recent unexpected finding in out laboratory is that there is sufficient amino ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/00A01K67/027A61K35/76A61K38/00A61K39/00A61K39/215A61K39/245A61K39/255A61K39/265A61K39/275A61K39/295A61K48/00A61P31/00A61P31/12A61P31/20A61P31/22A61P37/04C07K14/03C07K14/035C07K14/055C12N1/15C12N1/19C12N1/21C12N5/10C12N7/00C12N7/01C12N7/04C12N9/02C12N9/12C12N15/00C12N15/09C12N15/38C12N15/45C12N15/869C12P21/02C12R1/91C12R1/92
CPCA61K39/245A61K39/255A61K2039/51A61K2039/5254A61K2039/5256C07K14/005C12N9/0093C12N9/1211C12N15/00C12N15/86C12N2710/16022C12N2710/16034C12N2710/16043C12N2710/16322C12N2710/16334C12N2710/16343A61K38/00A61K39/00A61K39/12A61P31/00A61P31/12A61P31/20A61P31/22A61P37/04
Inventor GRIFFIN, ANNETTE MARYROSS, LOUIS JOSEPH NORMANSCOTT, SIMON DAVIDBINNS, MATTHEW MCKINLEY
Owner MERIAL SAS
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