Mosaic infectious bursal disease virus vaccines

Abstract

The invention relates to Infectious Bursal Disease Virus (“IBDV”) and vaccines therefor. Provided are infectious recombinant Infectious Bursal Disease Virus (“rIBDV”) essentially incapable of growing in a cell that is not derived from a bursa cell, or an infectious rIBDV having retained at least part of the very virulent characteristics of a very virulent Infectious Bursal Disease Virus (“vvIBDV”).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of co-pending U.S. patent application Ser. No. 10 / 046,671, filed Jan. 14, 2002, now U.S. Pat. No. ______, which application is a continuation of International Application Number PCT / NL00 / 00493 filed on Jul. 13, 2000 designating the United States of America, International Publication No. WO 01 / 04319 (Jan. 18, 2001), the contents of the entirety of each of which are incorporated by this reference.STATEMENT ACCORDING TO 37 C.F.R. § 1.52(e)(5)—SEQUENCE LISTING SUBMITTED ON COMPACT DISC [0002] Pursuant to 37 C.F.R. § 1.52(e)(1)(ii), a compact disc containing an electronic version of the Sequence Listing has been submitted concomitant with this application, the contents of which are hereby incorporated by reference. A second compact disc is submitted and is an identical copy of the first compact disc. The discs are labeled “copy 1” and “copy 2,” respectively, and each disc contains one file entitled “Rev. Sequ...

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Benefits of technology

[0040] In yet another embodiment, provided is a mosaic IBDV according to the invention wherein at least one of the isolates is a serotype II IBDV. Such an mIBDV, preferably lacking at least one immunodominant epitope specific for a serotype I IBDV as well, is an (r)D6948-derived vaccine virus such as mD6948-s2VP3C1, also having a functional VP2 protein derived from vvIBDV, allowing vaccination with a marker vaccine. Vaccination with an IBDV marker vaccine and subsequent testing with a corresponding diagnostic test enables the discrimination between antibodies induced by the vaccine and by infection with IBDV field isolates. This mIBDV can be differentiated from all other known wild-type IBDV isolates, either belonging to serotype I or serotype II, for example, by using a specific set of monoclonal antibodies. The generation of mIBDV from serotype I and II cDNA provides such an mIBDV marker vaccine that induces a serological response in chickens that can be differentiated from the serological response induced by IBDV field strains. The marker vaccine provided by the invention, lacking at least one immunodominant epitope, preferably a serotype I epitope, enables the discrimination between vaccinated and infected animals by means of a diagnostic serologic test. Such an mIBDV marker vaccine is preferably based upon vvIBDV and contains specific sequences originating from classical serotype I or serotype II IBDV. Such an mIBDV marker vaccine has one or more of the following characteristics: i) It induces a protective immune response against vvIBDV field viruses despite high levels of maternal antibodies. ii) It has a reduced pathogenicity compared to vaccines based upon wild-type vvIBDV. iii) It, for example, misses at least one serotype I-specific antigen which enables the serological discrimination of the mIBDV marker vaccine from all serotype I IBDV isolates.

[0042] Mutations or deletions in the mIBDV cDNA yields an mIBDV with a desired phenotype, i.e., mIBDV which is based on a very virulent isolate but which has a reduced ability to replicate and hence a reduced pathogenicity. The introduction of cDNA sequences from a serotype II, cell culture adapted, IBDV isolate (TY89) into the mosaic virus gives us yet another opportunity to generate marker mIBDV vaccine which can be discriminated from wild-type serotype I IBDV, for example, by using specific monoclonal antibodies. Such mIBDV can be used to induce an antibody spectrum, which differs from the spectrum induced by IBDV field isolates. This enables the development of a serologic test to determine whether IBDV antibodies are the result of live mIBDV vaccination or of infection with IBDV field isolates. For example, the mCEF94-s2VP3C virus is recognized by serotype II-specific VP3 antibody (Mab T75), while it is also recognized by a serotype I-specific VP2 antibody (Mab 1.4). This particular rIBDV is, on the other hand, not recognized by a serotype I-specific VP3 antibody (Mab B10). No apparent difference is present between the replication of mCEF94-s2VP3C and rCEF94, indicating that the exchange of the VP3C-terminal part does not lead to major changes in replication ability in QM5 cells. When, on the other hand, the complete VP3-encoding region was exchanged, we observed a severe reduction in replication ability of the resulting virus (mCEF94-s2VP3). On the other hand, mCEF94-s2VP3N was not reacting with Mab C3 (VP3, serotype I) while it is fully reacting with Mab B10 (VP3, serotype I) and only partially with Mab T75 (VP3, serotype II). Replication of this mosaic IBDV on CEF cells is reduced compared to rCEF94. From the generated mIBDV, based on cDNA derived from serotype I (CEF94) and serotype II (TY89), it is clear that a serological marker based on VP3 has been identified. The replacement of the cDNA of (part of) VP3 of serotype I for the corresponding part of serotype II leads to a unique combination of IBDV antigens within one mIBDV isolate. An mIBDV isolate based on this combination of antigens can be used as an IBDV marker vaccine.

[0043] The introduction of the VP3 C-terminal part of TY89 (Serotype II) into the cDNA of D6948 yielded a mosaic IBDV (mD6948-s2VP3C1) which has a reduced virulence (no mortality, no body weight loss) compared to D6948 or rD6948 (Table 6). This mIBDV, or a comparable isolate which is more or less virulent, is also advantageously used as an IBDV marker vaccine to prevent infections with very virulent IBDV field isolates.

Problems solved by technology

Essentially incapable of growing herein means that the isolate in question is not or only little capable to infect, multiply or be released for further replication.

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