Vaccination of cattle with synthetic peptides corresponding to predicted extracellular domains of Rhipicephalus (Boophilus) microplus Aquaporin-2 reduces the number of ticks feeding to repletion

Authors: Scoles, Glen; HUSSEIN, HALA - Washington State University; OLDS, CASSANDRA - Kansas State University; Mason, Kathleen; Davis, Sara

Submitted to: Parasites & Vectors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/17/2022
Publication Date: 2/8/2022
Citation: Scoles, G.A., Hussein, H.E., Olds, C.L., Mason, K.L., Davis, S.K. 2022. Vaccination of cattle with synthetic peptides corresponding to predicted extracellular domains of Rhipicephalus (Boophilus) microplus Aquaporin-2 reduces the number of ticks feeding to repletion. Parasites & Vectors. https://doi.org/10.1186/s13071-022-05166-1.
DOI: https://doi.org/10.1186/s13071-022-05166-1

Interpretive Summary: Vaccinating cattle to protect them from ticks can be a very cost effective and environmentally friendly way of preventing transmission of tick-borne disease and preventing the animal health concerns and production losses related to large numbers of ticks feeding on cattle. Historically there have been efforts to develop vaccines to protect cattle from invasive cattle fever ticks. While these vaccines were able to provide some protection, they have not been a commercial success because of variable effectiveness and the need for frequent re-vaccination to maintain acceptable levels of protection. No commercial vaccines to protect cattle from ticks are currently available in the US. ARS scientists have been conducting research to develop new vaccines that could protect cattle from ticks and tick-borne disease in a more consistent and cost effective way. This publication reports a study to test one new vaccine target, which is a protein in the gut of the tick, and a novel method of vaccinating cattle for such a target using short fragments of the protein called peptides. Using this approach the cattle were stimulated to develop antibodies against the target protein and this immune response lead to 25% reduction in the number of ticks that fed successfully on the vaccinated cattle. The data provided in this paper suggests that antibodies against peptide domains of concealed tick antigens can reduce tick survival on vaccinated animals, but additional study will be needed to completely understand how it works and if it can be an effective component of a future vaccine. Effective anti-tick vaccines can reduce costs, improve animal welfare, and protect humans and the environment from exposure to toxic pesticide residues.

Technical Abstract: Background: There have been ongoing efforts to identify anti-tick vaccine targets to protect cattle from infestation with cattle fever ticks Rhipicephalus (Boophilus) microplus. Two commercial vaccines based on the tick gut protein Bm86 have had variable effectiveness, which has led to poor acceptance, and numerous studies have attempted to identify vaccine antigens that will provide more consistently effective protection. Transcriptomic analysis of R. microplus led to identification of three aquaporin genes annotated to code for transmembrane proteins involved in the transport of water across cell membranes. Previous work showed that vaccination with full-length recombinant aquaporin 1 (RmAQP1) reduced tick burdens on cattle. Targeted silencing of aquaporin 2 (RmAQP2) expression suggested it might also be a good anti-tick vaccination target. Methods: Three synthetic peptides from the predicted extracellular domains of RmAQP2 were used to vaccinate cattle. Peptides were conjugated to keyhole limpet hemocyanin (KLH) as an antigenic carrier molecule. We monitored the antibody response with ELISA and challenged vaccinated cattle with R. microplus larvae. Results: There was a 25% reduction overall in the numbers of ticks feeding to repletion on the vaccinated cattle. Immune sera from vaccinated cattle recognized native tick proteins on a western blot and reacted to the three individual synthetic peptides in an ELISA. The vaccinated calf with the highest total IgG titer was not the most effective at controlling ticks; ratios of IgG isotypes 1 and 2 differed greatly among the three vaccinated cattle; the calf with the highest IgG1/IgG2 ratio had the fewest ticks. Ticks on vaccinated cattle had significantly greater replete weights compared to ticks on controls, mirroring results seen with RNA silencing of RmAQP2. However, protein data could not confirm that vaccination had any impact on the ability of the tick to concentrate its blood meal by removing water. Conclusions: A reduced number of ticks feed successfully on cattle vaccinated to produce antibodies against the extracellular domains of RmAQP2. However, our predicted mechanism, that antibody binding blocks the ability ofRmAQP2 to move water out of the blood meal, could not be confirmed. Further study will be required to define the the mechanism of action and to determine whether these vaccine targets will be useful components of an anti-tick vaccine cocktail.