Southern cattle tick vaccine product
Inventors
PEREZ DE LEON, ADALBERTO A • Briggs, Robert E • Tatum, Fred M • Miller, Robert • Guerrero, Felicito
Assignees
US Department of Agriculture USDA
Publication Number
US-11690901-B2
Publication Date
2023-07-04
Expiration Date
2041-03-02
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Abstract
This invention relates to novel fusion peptides and immunogenic compositions containing the fusion peptides useful in the control and prevention of tick infestations. The invention also relates to compositions comprising said fusion peptides, methods of vaccination against tick infestation using said fusion peptides and compositions, and kits for use with such compositions and methods.
Core Innovation
This invention relates to novel fusion peptides and immunogenic compositions containing fusion peptides useful in the control and prevention of tick infestations, specifically targeting Rhipicephalus (Boophilus) microplus, the southern cattle fever tick (SCFT). The invention further encompasses compositions comprising these fusion peptides, vaccination methods against tick infestations using such peptides and compositions, and kits associated with these methods and products.
The problem being solved arises from the significant economic impact of the SCFT, which is an important external parasite of livestock worldwide and a vector for bovine babesiosis and anaplasmosis. Existing vaccines, such as Combavac 3 in 1 and Bm86 immunomodulator, have limitations: Combavac 3 in 1 is not registered in the USA and only protects against the pathogens, not the ticks, while Bm86 provides high protection against R. annulatus but only limited (30-40%) effectiveness against R. microplus and requires multiple booster injections. Additionally, production issues, such as low yield in yeast for RmAQP1 antigen, complicate vaccine development.
The invention presents a modified Mannheimia haemolytica lktCA gene cluster cassette containing a polynucleotide encoding an added leukotoxin neutralizing epitope combined with at least one copy of a tick aquaporin 1 (AQP1) protein fragment and at least one copy of a tetanus toxin P2 epitope. This modified cassette expresses a chimeric protein that elicits immune responses providing protection against R. microplus ticks. The use of the modified M. haemolytica strain as a vector, which expresses an inactive but immunogenic leukotoxin (genetic toxoid), represents a novel approach for delivering tick aquaporin antigens to provoke immune responses in susceptible animals.
Claims Coverage
The patent includes three main independent claims focusing on novel polynucleotides and modified gene cluster cassettes.
Polynucleotide encoding tick aquaporin 1 fragment and tetanus toxin P2 epitope
A polynucleotide encoding at least one copy of an Rhipicephalus microplus aquaporin 1 protein fragment comprising the amino acid sequence set forth in SEQ ID NO: 16 and at least one copy of a tetanus toxin P2 epitope comprising the amino acid sequence set forth in SEQ ID NO: 14.
Composition comprising the polynucleotide
A composition comprising the polynucleotide encoding the tick AQP1 fragment and tetanus toxin P2 epitope, wherein the composition may be a polynucleotide, plasmid, expression vector, or host cell.
Modified Mannheimia haemolytica lktCA gene cluster cassette
A modified M. haemolytica lktCA gene cluster cassette comprising an insertion of a polynucleotide encoding an additional leukotoxin neutralizing epitope with amino acid sequence set forth in SEQ ID NO: 9 and the aforementioned polynucleotide encoding tick AQP1 and P2 epitope inserted downstream of the native leukotoxin A start codon.
The claims collectively cover polynucleotides encoding fusion proteins of tick AQP1 and tetanus P2 epitopes, compositions thereof, and modified M. haemolytica gene cluster cassettes incorporating these sequences along with a leukotoxin neutralizing epitope, providing means for producing vaccines and immunogenic compositions against tick infestation.
Stated Advantages
The vaccine compositions provide consistent and efficacious protection against R. microplus tick infestations.
The modified M. haemolytica vector can be produced in useful quantities, overcoming prior antigen production issues.
The fusion of P2 epitopes enhances immune response activation in ruminants, facilitating B and T cell activation.
The vector strain expressing inactive but immunogenic leukotoxin is attenuated yet retains colonization ability and induces neutralizing antibodies.
Documented Applications
Control and prevention of Rhipicephalus microplus tick infestation in cattle and related animals.
Use as a vaccine or immunogenic composition for injectable, intranasal, or oral delivery to cattle, bison, deer, and other mammals.
Compositions and methods to induce immune responses in mammals, including cattle, sheep, goats, pigs, bison, elk, camels, dogs, and deer.
Potential combination with vaccines against other bovine pathogens such as Pasteurella multocida, Histophilus somni, BHV-1, PI-3V, and BRSV.
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