Recombinant vaccine against Marek's disease and Newcastle disease
Inventors
Yu, Qingzhong • Spatz, Stephen J. • Dunn, John R.
Assignees
US Department of Agriculture USDA
Publication Number
US-11299517-B2
Publication Date
2022-04-12
Expiration Date
2040-04-15
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Abstract
Provided herein are immunogenic compositions containing recombinant viruses capable of inducing protection in poultry against both Marek's disease virus (MDV) and Newcastle disease virus (NDV). Such viruses incorporate nucleic acids for expressing at least one MDV antigen, such as glycoprotein B, and antigenic portions thereof, in a recombinant NDV genome.
Core Innovation
The invention provides immunogenic compositions containing recombinant viruses capable of inducing protection in poultry against both Marek's disease virus (MDV) and Newcastle disease virus (NDV). These recombinant viruses express at least one MDV antigen, such as glycoprotein B (gB), in a recombinant NDV genome, specifically based on the NDV LaSota strain. The vaccines induce simultaneous immunity against both MDV and NDV, enabling dual protection.
The problem addressed is the limitations of current vaccines against Marek's disease and Newcastle disease. Existing MDV vaccines are unstable at temperatures above -80°C, requiring a cold chain and liquid nitrogen storage which is impractical in many countries, leading to vaccine failure or inability to vaccinate effectively. Additionally, commercially prevalent live and vectored vaccines do not elicit sterilizing immunity and can be costly to produce, store, and ship. There is a pressing need for a stable, safe, effective, inexpensive, and easy-to-administer dual vaccine that overcomes these challenges.
To solve this, the invention develops a recombinant NDV LaSota vaccine strain expressing the MDV glycoprotein B gene optimized for codon usage in chickens. This recombinant virus (rLS/MDV-gB) was generated via reverse genetics technology. Biological assessments demonstrated that rLS/MDV-gB maintains similar growth kinetics to parental strains, is slightly attenuated in vivo, and effectively expresses MDV glycoprotein B in infected cells. Vaccination with this recombinant virus in chickens conferred significant protection against virulent MDV challenge and full protection against velogenic NDV challenge, establishing a safe, stable, inexpensive, and effective bivalent vaccine.
Claims Coverage
The patent contains three independent claims covering a composition, a vector, and a method for eliciting an immune response using recombinant NDV expressing MDV antigens. The main inventive features relate to specific nucleic acid sequences, synthetic polypeptides, recombinant NDV constructs, and their administration to poultry.
Composition comprising a nucleic acid at least 95% identical to SEQ ID NO:3
The invention relates to an immunogenic composition comprising a nucleic acid sequence that is at least 95% identical to SEQ ID NO:3, encoding the recombinant NDV genome containing the MDV glycoprotein B gene.
Vector containing nucleic acid encoding synthetic polypeptide at least 95% identical to SEQ ID NO:2
A vector comprising the nucleic acid encoding a synthetic polypeptide having at least 95% amino acid sequence identity to SEQ ID NO:2, which corresponds to the MDV glycoprotein B expressed in the recombinant NDV vector, including embodiments identical to SEQ ID NO:2 and at least 99% identical nucleic acid sequences.
Method of eliciting immune response against MDV and NDV by administering recombinant NDV
A method for eliciting an immune response against Marek's disease virus and Newcastle disease virus by administering to a subject, preferably poultry such as chicken, a composition comprising a recombinant NDV carrying a nucleic acid at least 95% identical to SEQ ID NO:3 encoding the synthetic polypeptide at least 95% identical to SEQ ID NO:2.
In summary, the claims cover compositions and vectors comprising nucleic acid sequences encoding MDV glycoprotein B inserted into a recombinant NDV LaSota strain, and methods of vaccination using these recombinant viruses to protect poultry against both Marek's disease and Newcastle disease.
Stated Advantages
The recombinant NDV-based vaccine is safe, stable, and slightly attenuated compared to parental strains, minimizing pathogenicity risks.
It is inexpensive to produce, store, and transport, eliminating the need for a stringent cold chain or liquid nitrogen storage, allowing administration at ambient temperatures.
The vaccine provides effective bivalent protection against both Marek's disease and Newcastle disease in chickens, including early partial protection against MDV.
The recombinant NDV vector can be administered via multiple practical methods, such as drinking water or spray, facilitating large-scale poultry vaccination.
Documented Applications
Vaccination of poultry, particularly chickens, against Marek's disease virus (MDV) and Newcastle disease virus (NDV) to prevent clinical disease and mortality.
Administration of recombinant NDV-based dual vaccine through drinking water, direct spray, intranasal or intraocular routes, or in ovo injection to induce immunity in commercial poultry.
Use in industrialized and developing countries where cold chain maintenance is difficult, enabling effective vaccination against Marek's disease and Newcastle disease without liquid nitrogen storage.
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