Aquaporin 2 protects cattle from ticks and tick-borne parasites
Inventors
Scoles, Glen A. • Guerrero, Felicito • Bastos, Reginaldo
Assignees
US Department of Agriculture USDA • Washington State University WSU
Publication Number
US-10722561-B2
Publication Date
2020-07-28
Expiration Date
2036-06-09
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Abstract
A novel method of using an aquaporin protein from Rhipicephalus microplus (RmAQP2), fragments of RmAQP2, and/or the cDNA encoding RmAQP2 and/or the fragments are described. Immunogenic composition containing recombinant RmAQP2 and/or fragments of RmAQP2 are produced and administered to an ungulate which generates an immune response to RmAQP2. After feeding female ticks on the ungulate injected with RmAQP2 and/or fragments of RmAQP2, the female ticks have lower reproductive viability because of a reduced egg mass, reduced hatching percentage, and reduced survival of larvae. Thus, administering RmAQP2 and/or RmAQP2 fragments to an ungulate can reduce the incidence of R. microplus and also reduce the incidence of tick-borne pathogens in ungulates because of the lower number of R. microplus.
Core Innovation
This invention relates to the identification and use of an aquaporin 2 protein (RmAQP2) from the cattle tick Rhipicephalus microplus and immunogenic compositions containing this protein or fragments thereof. The invention provides novel methods for protecting cattle and other ungulates against infestations by R. microplus ticks and the transmission of tick-borne pathogens, such as Babesia bovis, through the administration of immunogenic compositions that elicit an immune response to RmAQP2 in the host animal.
The problem addressed by the invention is the significant economic impact of R. microplus as a vector of bovine babesiosis and the limitations of existing control methods. Current control strategies rely heavily on acaricides and live attenuated vaccines, both of which have drawbacks including inconsistent efficacy, development of acaricide resistance, and the reemergence of ticks in previously controlled areas. There is a need for a more effective vaccine strategy that disrupts tick feeding or reproduction, thereby reducing tick infestation rates and pathogen transmission.
The invention provides immunogenic compositions comprising RmAQP2 protein, fragments thereof, or polynucleotides encoding RmAQP2, which, upon administration to ungulates, induce an immune response that reduces tick reproductive viability. Ticks feeding on immunized animals show reduced egg mass, lowered hatching percentages, and decreased survival of larvae. This ultimately leads to a reduction in tick population and a concomitant decrease in transmission of tick-borne pathogens. The invention also includes expression vectors, recombinant organisms expressing RmAQP2, and kits containing immunogenic compositions and administration instructions.
Claims Coverage
The patent includes multiple independent claims focused on expression vectors encoding RmAQP2 or its fragments, immunogenic compositions containing these vectors or recombinant organisms, and their use in generating immune responses to control tick populations.
Expression vectors encoding RmAQP2 or its fragments
Comprise a heterologous promoter operably linked to polynucleotides encoding RmAQP2 immunogens, including full-length and fragments with specified sequences (e.g., amino acids 3-293 of SEQ ID NO: 2 and peptides represented by SEQ ID NO: 13, 14, 15, 27), as well as sequences at least 95%-97% identical to these.
Immunogenic compositions containing expression vectors
Immunogenic compositions comprising the expression vectors encoding RmAQP2 or fragments thereof together with a pharmaceutically acceptable carrier and optionally an adjuvant, designed to induce an immune response in ungulates.
Recombinant organisms expressing RmAQP2
Recombinant organisms comprising the expression vectors encoding RmAQP2 or its fragments, which can be used in immunogenic compositions to stimulate an immune response.
Expression vectors encoding polynucleotides with specific DNA sequences
Include polynucleotides with specified DNA sequences (SEQ ID NOs: 1, 3, 4, 6, 8, 10, 24, 25, 26, 28, and sequences at least 95%-97% identical thereto) operably linked to heterologous promoters for expression of RmAQP2 immunogens.
The independent claims cover molecular constructs encoding RmAQP2 or immunologically active fragments, their incorporation into vaccine compositions and recombinant organisms, and the DNA sequences encoding these proteins or fragments, all aimed at eliciting protective immune responses in ungulates to control tick infestations and tick-borne diseases.
Stated Advantages
Administration of RmAQP2 or its fragments to ungulates reduces the viability of R. microplus offspring, lowering egg mass, hatch rates, and larval survival.
Reduced tick populations lead to decreased incidence of tick infestations in cattle and other ungulates.
Lower number of ticks reduces the transmission of tick-borne pathogens such as Babesia bovis, B. bigemina, and Anaplasma marginale.
Documented Applications
Use of immunogenic compositions containing RmAQP2 or fragments thereof as vaccines to protect cattle and other ruminants from infestations by R. microplus.
Reduction of tick reproductive viability and tick population density on vaccinated ungulates.
Prevention or reduction of transmission of tick-borne diseases including bovine babesiosis caused by B. bovis, as well as diseases caused by B. bigemina and Anaplasma marginale.
Use of recombinant organisms expressing RmAQP2 or DNA vaccines encoding RmAQP2 for immunization against tick infestations and tick-borne diseases.
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