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PreprintCited by 4Vector-borne infectious diseasesvaccines and immunoinformatics approachesStudy of Mite Species

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Leading anti-tick vaccine targets are variably conserved in cattle fever ticks

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Busch, Joseph D., Stone, Nathan E., Pemberton, Grant L., Roberts, Mackenzie L., Turner, Rebekah E., Thornton, Natalie B., Sahl, Jason W., Lemmer, Darrin, Buckmeier, Greta, Davis, Sara K., Guerrero-Solorio, Roberto I., Karim, Shahid, Klafke, Guilherme, Thomas, Donald B., Olafson, Pia U., Ueti, Massaro, Mosqueda, Juan, Scoles, Glen A., Wagner, David M.·2024·Parasites & Vectors
DOI 10.21203/rs.3.rs-4844765/v1PMC PMC12001435

Preprint — published as 10.1186/s13071-025-06683-5 · Paper page

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Abstract

Background Rhipicephalus (Boophilus) microplus causes significant cattle production losses worldwide because it transmits Babesia bovis and B. bigemina causative agents of bovine babesiosis. Control of these ticks primarily has relied on treatment of cattle with chemical acaricides, but frequent use, exacerbated by the one-host life cycle of these ticks, has led to high-level resistance to multiple classes of acaricides. Consequently, new approaches for control, such as anti-tick vaccines, are critically important. Key to this approach is targeting highly conserved antigenic epitopes to reduce the risk of vaccine escape in heterologous tick populations. Methods We evaluated amino acid conservation within 14 tick proteins across 167 R. microplus collected from geographically diverse locations in the Americas and Pakistan using PCR amplicon sequencing and in silico translation of exons. Results We found that amino acid conservation varied considerably across these proteins. Only one target, the voltage-dependent anion channel, was fully conserved in all 167 R. microplus samples (protein similarity 1.0). Five other proteins were highly conserved: the aquaporin RmAQP1 (0.989), vitellogenin receptor (0.985), serpin-1 (0.985), and subolesin (0.981). In contrast, the glycoprotein protease Bm86 was one of the least conserved (0.889). The Bm86 sequence used in the original Australian TickGARD vaccine carried many amino acid replacements compared to the R. microplus populations examined here, supporting the hypothesis that this vaccine target is not optimal for use in the Americas. By mapping amino acid replacements onto predicted 3D protein models, we also identified amino acid changes within several small peptide vaccines targeting portions of the aquaporin RmAQP2, chitinase, and Bm86. Conclusions These findings emphasize the importance of thoroughly analyzing protein variation within anti-tick vaccine targets across diverse tick populations before selecting candidate vaccine antigens. When considering protein conservation alone, RmAQP1, vitellogenin receptor, serpin-1, subolesin, and especially the voltage-dependent anion channel rank as high priority anti-tick vaccine candidates for use in the Americas and perhaps globally.

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Fig. 1 Protein conservation in 14 anti-tick targets evaluated in 167 samples of Rhipicephalus (Boophilus) microplus from North America (n = 145), South America (n = 17), and Pakistan (n = 5). The y-axis shows protein similarity; the x-axis is set to cross the y-axis at 0.80. Proteins are ranked from most to least conserved; the Bm86 protein (red box) used in all first-generation cattle vaccines is one of the least conserved proteins in our study
Fig. 1 Protein conservation in 14 anti-tick targets evaluated in 167 samples of Rhipicephalus (Boophilus) microplus from North America (n = 145), South America (n = 17), and Pakistan (n = 5). The y-axis shows protein similarity; the x-axis is set to cross the y-axis at 0.80. Proteins are ranked from most to least conserved; the Bm86 protein (red box) used in all first-generation cattle vaccines is one of the least conserved proteins in our studyCC BY · PubMed Central
Fig. 2 Locations of amino acid replacements in 10-aa windows of the 14 proteins analyzed in this study. Only replacements identified in the Rhipicephalus (Boophilus) microplus samples from our study (n = 167) are used. Amino acid positions are shown on the top scale. Outlined boxes indicate each full-length protein except for VgR; the VgR boxes outline two ligand binding domains (LBDs) that were assayed in this study. Shading key: blue = conserved positions; orange to red = 1–5 replacements per window of 10 amino acids; white = missing data
Fig. 2 Locations of amino acid replacements in 10-aa windows of the 14 proteins analyzed in this study. Only replacements identified in the Rhipicephalus (Boophilus) microplus samples from our study (n = 167) are used. Amino acid positions are shown on the top scale. Outlined boxes indicate each full-length protein except for VgR; the VgR boxes outline two ligand binding domains (LBDs) that were assayed in this study. Shading key: blue = conserved positions; orange to red = 1–5 replacements per window of 10 amino acids; white = missing dataCC BY · PubMed Central
Fig. 3 Location of amino acid replacements (blue) mapped onto predicted 3D structural models of selected proteins: A voltage-dependent anion channel (RmVDAC); B vitellogenin receptor (VgR); C aquaporin-1 (RmAQP1); D serine protease inhibitor-1 (RmS-1); E subolesin (RmSub); F aquaporin-2 (RmAQP2); G chitinase (Chit); H glycoprotein Bm86 (Bm86). Published short-peptide vaccine targets (magenta) are highlighted for RmAQP2, Chit, RmSub, and Bm86; magenta is also used to highlight two lipid-binding domains (LBDs) that were assayed in VgR. Only those replacements identified in our Rhipicephalus (Boophilus) microplus dataset from the Americas and Pakistan are highlighted; additional replacements identified from previously published sequences of R. microplus and other Rhipicephalus species are documented in the amino acid alignments within Additional file 6. All 3D protein models were generated using the Alphafold website; specific URL addresses for each protein are provided
Fig. 3 Location of amino acid replacements (blue) mapped onto predicted 3D structural models of selected proteins: A voltage-dependent anion channel (RmVDAC); B vitellogenin receptor (VgR); C aquaporin-1 (RmAQP1); D serine protease inhibitor-1 (RmS-1); E subolesin (RmSub); F aquaporin-2 (RmAQP2); G chitinase (Chit); H glycoprotein Bm86 (Bm86). Published short-peptide vaccine targets (magenta) are highlighted for RmAQP2, Chit, RmSub, and Bm86; magenta is also used to highlight two lipid-binding domains (LBDs) that were assayed in VgR. Only those replacements identified in our Rhipicephalus (Boophilus) microplus dataset from the Americas and Pakistan are highlighted; additional replacements identified from previously published sequences of R. microplus and other Rhipicephalus species are documented in the amino acid alignments within Additional file 6. All 3D protein models were generated using the Alphafold website; specific URL addresses for each protein are providedCC BY · PubMed Central

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Metadata

Authors
Busch, J. D., Stone, N. E., Pemberton, G. L., Roberts, M. L., Turner, R. E., Thornton, N. B., Sahl, J. W., Lemmer, D., Buckmeier, G., Davis, S. K., Guerrero-Solorio, R. I., Karim, S., Klafke, G., Thomas, D. B., Olafson, P. U., Ueti, M., Mosqueda, J., Scoles, G. A., & Wagner, D. M.
Affiliations
  • Northern Arizona University (US)
  • Translational Genomics Research Institute (US)
  • Agricultural Research Service (US)
  • Washington State University (US)
  • Autonomous University of Queretaro (MX)
  • University of Southern Mississippi (US)
  • Instituto de Pesquisas Veterinarias Desidério Finamor
Corresponding author
Busch, Joseph D.
ORCID
Venue
Parasites & Vectors
Publisher
Springer Science and Business Media LLC
Published
2024-08-28
Volume
18
Issue
1
Pages
140-140
ISSN
1756-3305 (ISSN-L)
DOI
10.21203/rs.3.rs-4844765/v1
PMC
PMC12001435
OpenAlex
W4409445452
Cited by
4
References
1
Citations by year
2026: 2 · 2025: 2
FWCI
3.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Parasites & Vectors (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Aquila Digital Community (University of Southern Mississippi) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of State (PGA-P21049)
  • U.S. Department of Agriculture
  • Texas Animal Health Commission
  • Northern Arizona University
  • National Institute of Food and Agriculture (2015-67015-23047)
  • Agricultural Research Service (NACA 2021 58-2090-1-037)
  • Animal and Plant Health Inspection Service
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Study of Mite Species
Keywords
Rhipicephalus microplus, cattle ticks, tick vaccine, amino acid sequence variation, voltage-dependent anion channel, vitellogenin receptor, subolesin, vaccine escape, bovine babesiosis, tick acaricide resistance, vaccine antigen selection
MeSH terms
Americas, Amino Acid Sequence, Animals, Epitopes, Babesiosis, Cattle, Cattle Diseases, Pakistan, Tick Infestations, Vaccines, Conserved Sequence, Rhipicephalus, Arthropod Proteins

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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This page
CoChat. (2026). Citation check: Leading anti-tick vaccine targets are variably conserved in cattle fever ticks. https://app.cochat.ai/papers/10.21203/rs.3.rs-4844765/v1
The paper
Busch, J. D., Stone, N. E., Pemberton, G. L., Roberts, M. L., Turner, R. E., Thornton, N. B., Sahl, J. W., Lemmer, D., Buckmeier, G., Davis, S. K., Guerrero-Solorio, R. I., Karim, S., Klafke, G., Thomas, D. B., Olafson, P. U., Ueti, M., Mosqueda, J., Scoles, G. A., & Wagner, D. M. (2024). Leading anti-tick vaccine targets are variably conserved in cattle fever ticks. Parasites & Vectors. https://doi.org/10.21203/rs.3.rs-4844765/v1

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.