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

The DOI matches its Crossref record; 136 of the 136 references it cites were found in a registry or an index.

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

Open access
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.·2025·Parasites & Vectors
DOI 10.1186/s13071-025-06683-5PMC PMC12001435

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Abstract

Background: Rhipicephalus ( Boophilus ) microplus causes significant cattle production losses worldwide because it transmits Babesia bovis and B. bigemina , the causative agents of bovine babesiosis. Control of these ticks has primarily relied on treatment of cattle with chemical acaricides, but frequent use, exacerbated by the one-host lifecycle 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 polymerase chain reaction (PCR) amplicon sequencing and in silico translation of exons. Results: We found that amino acid conservation varied considerably across these proteins. Only the voltage-dependent anion channel (VDAC) was fully conserved in all R. microplus samples (protein similarity 1.0). Four 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 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 with 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 three-dimensional (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 VDAC rank as high-priority anti-tick vaccine candidates for use in the Americas and perhaps globally.

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Crossref · 10.1186/s13071-025-06683-5

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Figures

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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Citations

Cites

Research works printed but not linked: 5

  1. Wikel SK, Allen JR. Immunological basis of host resistance to ticks. Physiology of ticks. Amsterdam: Elsevier; 1982. p. 169–96.
  2. Cobon G, Hungerford J, Woodrow M, Smith D, Willadsen P. Vaccination against Boophilus microplus: the Australian field experience. In: Fuente JDL, editor. Recombinant vaccines for the control of cattle tick. La Habana: Elfos Scientiae; 1995. p. 163–76.
  3. Martínez-Maza NT, Hernández-Ortiz R, Valdez-Espinoza UM, Castro-Saines E, Aguilar-Díaz H, Lagunes-Quintanilla R. Molecular analysis of a polypeptide of the RmS-17 protein for the development of a vaccine against Rhipicephalus microplus ticks in Mexico. Ecosistemas y recursos agropecuarios. 2020;7:e2537.
  4. Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Widows 95/98/NT. Nucleic Acids Symp Ser. 1999;41:95–8.
  5. Freeman JM, Davey RB, Kappmeyer LS, Kammlah DM, Olafson PU. Bm86 midgut protein sequence variation in South Texas cattle fever ticks. Parasit Vectors. 2010;3:101. · DOI

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)
Corresponding author
Busch, Joseph D.
ORCID
Venue
Parasites & Vectors
Publisher
Springer Science and Business Media LLC
Published
2025-04-15
Volume
18
Issue
1
Pages
140-140
ISSN
1756-3305 (ISSN-L)
DOI
10.1186/s13071-025-06683-5
PMC
PMC12001435
OpenAlex
W4409445452
Cited by
4
References
136
Citations by year
2026: 2 · 2025: 2
FWCI
3.57
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
  • USDA-NIFA-AFRI (2018-67015-28301)
  • USDA-APHIS-VS (AP20VSSPRS00C117)
  • USDA-ARS (NACA 2021 58-2090-1-037)
  • National Institute of Food and Agriculture (2015-67015-23047)
  • Northern Arizona University (Hooper Undergraduate Research Award (HURA) to R. E. Turner)
  • US Department of State Pakistan-US Science and Technology Cooperation Program Award (PGA-P21049)
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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