Vaccination of animals to elicit a protective immune response against tick infestations and tick-borne pathogen transmission
Inventors
Guerrero, JR., Felicito • Perez De Leon, Adalberto A.
Assignees
US Department of Agriculture USDA
Publication Number
US-8722063-B2
Publication Date
2014-05-13
Expiration Date
2032-05-24
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Two antigenic and immunogenic proteins of the cattle tick, Rhipicephalus microplus, and the genes encoding these proteins, are effective for eliciting a protective immune response that controls and prevents infestations of bovines and other livestock by the tick. The proteins isolated from the cattle tick include an aquaporin protein and a TC5777 gut membrane protein. Each of the proteins elicit an immunoprotective response in livestock to the cattle tick, and can be formulated and administered as vaccines. Alternatively, the isolated DNA sequences which encode these proteins can be incorporated into nucleic acid constructs which could be utilized as DNA vaccines. The nucleic acid constructs can also be used for the transformation of cells and the production of recombinant proteins. Induction of the protective immune response controls and prevents infestations of the treated animals with the tick, thereby protecting them against tick-borne pathogen transmission.
Core Innovation
The invention provides isolated immunogenic and antigenic proteins from the cattle tick, Rhipicephalus microplus, specifically an aquaporin protein fragment and a gut membrane protein known as TC5777. These proteins, and the genes encoding them, are capable of eliciting a protective immune response in livestock, including bovines, which significantly reduces or eliminates infestations by the cattle tick. The proteins can be formulated and administered as protein vaccines or used as DNA vaccines through nucleic acid constructs encoding these proteins that enable in vivo expression within vaccinated animals.
The background identifies a persistent problem: the resurgence risk of the cattle tick, R. microplus, in the United States, especially due to acaricide-resistant populations in Mexico. This tick transmits the protozoan agents Babesia bovis and B. bigemina, which cause cattle fever, a disease threatening livestock health. Conventional chemical acaricides face challenges including resistance and environmental concerns. Therefore, there is a need for effective, environmentally safe, and alternative techniques to control and prevent cattle tick infestations and thus reduce transmission of tick-borne pathogens.
In response to this problem, the invention discovers and isolates the immunogenic aquaporin and TC5777 proteins, sequences their amino acid and nucleic acid compositions, and demonstrates their utility as vaccines. The vaccines either include the protein antigens or nucleic acid constructs encoding these proteins, leading to protective immune responses that decrease tick infestation and consequentially reduce cattle fever incidence. The development includes methods for recombinant production of these proteins in vectors such as Pichia pastoris and expression plasmids for DNA vaccines, providing innovative approaches to tick control.
Claims Coverage
The patent includes multiple independent claims focused on the isolated aquaporin protein and compositions comprising this protein, with or without the TC5777 gut membrane protein, directed to vaccines and immunogenic compositions for cattle tick protection.
Isolated aquaporin protein specific to cattle tick
An isolated aquaporin protein of Rhipicephalus microplus comprising amino acids 3-198 of SEQ ID NO: 1, or sequences including amino acids 1-199 of SEQ ID NO: 1 and SEQ ID NO: 4, as well as recombinant forms with sequences of SEQ ID NO: 2 and SEQ ID NO: 3.
Immunogenic composition comprising aquaporin protein
A composition comprising an immunogenic amount of aquaporin protein with amino acids 3-198 of SEQ ID NO: 1 to stimulate an immune response in bovines, optionally including the Rhipicephalus microplus TC5777 gut membrane protein of SEQ ID NO: 9.
Pharmaceutically acceptable carriers and adjuvants for vaccine formulation
Formulations of the aquaporin protein vaccine with carriers selected from physiological saline, phosphate buffered saline, mineral oil, vegetable oils, aqueous carboxymethyl cellulose, and polyvinylpyrrolidone, optionally including adjuvants such as mineral oil, vegetable oil, alum, Freund's incomplete adjuvant, and biocompatible matrix materials like agar or polyacrylate.
Effective dosing of aquaporin protein in vaccine compositions
Immunogenic vaccine compositions containing greater than 10 μg protein per animal, preferably between about 50 to 150 μg protein per animal.
The claims collectively cover isolated aquaporin proteins and their immunogenic uses in vaccine compositions with specified amino acid sequences, vaccine formulation carriers and adjuvants, and effective antigen dosing for eliciting protective immune responses in cattle against Rhipicephalus microplus.
Stated Advantages
The invention provides immunogenic proteins and DNA constructs that elicit protective immune responses in livestock, effectively controlling and preventing cattle tick infestations.
The vaccine reduces the incidence of cattle fever by decreasing tick infestations and interrupting transmission of the Babesia pathogens.
The proteins and nucleic acid constructs can be produced recombinantly, enabling scalable and practical vaccine production.
The vaccines offer an environmentally safe alternative to conventional chemical acaricides, including for populations resistant to acaricides.
Documented Applications
Vaccination of livestock, including bovines like dairy cows and cattle, to control and prevent infestations by the cattle tick Rhipicephalus microplus.
Use of the vaccines to reduce or eliminate transmission of the cattle fever pathogens Babesia bovis and Babesia bigemina.
Production of recombinant aquaporin and TC5777 proteins using host cells such as Pichia pastoris for vaccine manufacture.
DNA vaccination through administration of nucleic acid constructs encoding the aquaporin and/or TC5777 proteins to elicit protective immune responses in treated animals.
Interested in licensing this patent?