Exploration of Immunology

Table 2. Search tools, bioinformatic web server names, and URLs necessary to predict subcellular localization, protein structure, immunogenic characteristics, and some other desirable features for vaccine development

Bioinformatic web servers	Search tools names and URLs
General sequences analysis	BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi)
	Pfam (https://www.ebi.ac.uk/interpro/)
	MESSA (http://prodata.swmed.edu/MESSA/MESSA.cgi)
	PDBsum (http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=index.html)
	KEGG (https://www.genome.jp/kegg/kegg2.html)
Secretion	SignalP 5.0 (https://services.healthtech.dtu.dk/service.php?SignalP-5.0)
	Sigcleave (https://www.bioinformatics.nl/cgi-bin/emboss/sigcleave)
	Phobius (https://phobius.sbc.su.se/index.html)
	PRED-SIGNAL (http://bioinformatics.biol.uoa.gr/PRED-SIGNAL/input.jsp)
Subcellular localization	TargetP 2.0 (https://services.healthtech.dtu.dk/service.php?TargetP-2.0)
	WoLF PSORT (https://www.genscript.com/wolf-psort.html)
	PSORTb (https://www.psort.org/psortb/)
Transmembranal helices	TMHMM 2.0 (https://services.healthtech.dtu.dk/service.php?TMHMM-2.0)
Transmembranal helices	Phobius (https://phobius.sbc.su.se/index.html)
B cell epitope predictors	ABCpred (https://webs.iiitd.edu.in/raghava/abcpred/ABC_submission.html)
	BepiPred 3.0 (https://services.healthtech.dtu.dk/service.php?BepiPred-3.0)
	Bcepred (https://webs.iiitd.edu.in/raghava/bcepred/bcepred_submission.html)
	DiscoTope (http://tools.iedb.org/discotope/)
	Pepitope (http://pepitope.tau.ac.il/)
	IEDB (https://www.iedb.org/)
T cell epitope predictors	NetCTLpan 1.1 (https://services.healthtech.dtu.dk/service.php?NetCTLpan-1.1)
	NetMHCpan 4.0 (https://services.healthtech.dtu.dk/service.php?NetMHCpan-4.0)
	TAPPred (http://crdd.osdd.net/raghava/tappred/)
	ProPred-I (http://crdd.osdd.net/raghava/propred1/)
	IMGT/LIGM-DB (https://www.imgt.org/ligmdb/)
	IEDB (https://www.iedb.org/)
	EpiJen v1.0 (http://www.ddg-pharmfac.net/epijen/EpiJen/EpiJen.htm)
	IPD-MHC (https://www.ebi.ac.uk/ipd/mhc/group/BoLA/)
In silico vaccine pipelines	VaxiJen v2.0 (http://www.ddg-pharmfac.net/vaxijen/VaxiJen/VaxiJen.html)
	NERVE (http://www.bio.unipd.it/molbinfo/NERVE_download.html)
	VIOLIN (https://violinet.org/)
	Vaxign (https://violinet.org/vaxign/)
	Vacceed (http://github.com/sgoodswe/vacceed)

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Declarations

Acknowledgments

We greatly appreciate the support received from Dr. Consuelo Almazán-García for her constructive comments made on the original draft of this manuscript.

Author contributions

RRC: Conceptualization, Formal analysis, Writing—original draft. DIDG: Formal analysis, Writing—original draft, Writing—review & editing. SLS: Formal analysis, Writing—original draft, Writing—review & editing. FRD: Resources, Writing—review & editing, Visualization.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Food and Agriculture Organization of the United Nations. La ganadería, a examen. El estado mundial de la agricultura y la alimentación [Internet]. Roma; c2009 [cited 2022 Nov 23]. Available from: https://www.fao.org/3/i0680s/i0680s.pdf

Prudencio CR, Marra AO, Cardoso R, Goulart LR. Recombinant peptides as new immunogens for the control of the bovine tick, Rhipicephalus (Boophilus) microplus. Vet Parasitol. 2010;172:122–31. [DOI] [PubMed]

Jensen K, de Miranda Santos IKF, Glass EJ. Using genomic approaches to unravel livestock (host)-tick-pathogen interactions. Trends Parasitol. 2007;23:439–44. [DOI] [PubMed]

Kongsuwan K, Josh P, Zhu Y, Pearson R, Gough J, Colgrave ML. Exploring the midgut proteome of partially fed female cattle tick (Rhipicephalus (Boophilus) microplus). J Insect Physiol. 2010;56:212–26. [DOI] [PubMed]

Riedel S. Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent). 2005;18:21–5. [DOI] [PubMed] [PMC]

Lombard M, Pastoret PP, Moulin AM. A brief history of vaccines and vaccination. Rev Sci Tech. 2007;26:29–48. [DOI] [PubMed]

Hellstrom KE, Hellstrom I. Novel approaches to therapeutic cancer vaccines. Expert Rev Vaccines. 2003;2:517–32. [DOI] [PubMed]

Fiore AE, Bridges CB, Cox NJ. Seasonal influenza vaccines. In: Compans R, Orenstein W, editor. Vaccines for pandemic influenza. Berlin, Heidelberg: Springer Berlin Heidelberg; 2009. pp. 43–82. [DOI] [PubMed]

Liesegang TJ. Varicella zoster virus vaccines: effective, but concerns linger. Can J Ophthalmol. 2009;44:379–84. [DOI] [PubMed]

10.

Chang Y, Brewer NT, Rinas AC, Schmitt K, Smith JS. Evaluating the impact of human papillomavirus vaccines. Vaccine. 2009;27:4355–62. [DOI] [PubMed]

11.

Poland GA, Ovsyannikova IG, Kennedy RB. Personalized vaccinology: a review. Vaccine. 2018;36:5350–7. [DOI] [PubMed] [PMC]

12.

Cotugno N, Ruggiero A, Santilli V, Manno EC, Rocca S, Zicari S, et al. OMIC technologies and vaccine development: from the identification of vulnerable individuals to the formulation of invulnerable vaccines. J Immunol Res. 2019;2019:8732191. [DOI] [PubMed] [PMC]

13.

Stutzer C, Richards SA, Ferreira M, Baron S, Maritz-Olivier C. Metazoan parasite vaccines: present status and future prospects. Front Cell Infect Microbiol. 2018;8:67. [DOI] [PubMed] [PMC]

14.

Rappuoli R. Reverse vaccinology. Curr Opin Microbiol. 2000;3:445–50. [DOI] [PubMed]

15.

Seib KL, Zhao X, Rappuoli R. Developing vaccines in the era of genomics: a decade of reverse vaccinology. Clin Microbiol Infect. 2012;18:109–16. [DOI] [PubMed]

16.

Gutiérrez AH, Spero D, Gay C, Zimic M, De Groot AS. New vaccines needed for pathogens infecting animals and humans. Hum Vaccin Immunother. 2012;8:971–8. [DOI] [PubMed]

17.

Omersel J, Karas Kuželički N. Vaccinomics and adversomics in the era of precision medicine: a review based on HBV, MMR, HPV, and COVID-19 vaccines. J Clin Med. 2020;9:3561. [DOI] [PubMed] [PMC]

18.

Poland GA, Kennedy RB, McKinney BA, Ovsyannikova IG, Lambert ND, Jacobson RM, et al. Vaccinomics, adversomics, and the immune response network theory: individualized vaccinology in the 21st century. Semin Immunol. 2013;25:89–103. [DOI] [PubMed] [PMC]

19.

Bragazzi NL, Gianfredi V, Villarini M, Rosselli R, Nasr A, Hussein A, et al. Vaccines meet big data: state-of-the-art and future prospects. From the classical 3Is (“isolate-inactivate-inject”) vaccinology 1.0 to vaccinology 3.0, vaccinomics, and beyond: a historical overview. Front Public Health. 2018;6:62. [DOI] [PubMed] [PMC]

20.

Wallis J, Shenton DP, Carlisle RC. Novel approaches for the design, delivery and administration of vaccine technologies. Clin Exp Immunol. 2019;196:189–204. [DOI] [PubMed] [PMC]

21.

Hicks DJ, Fooks AR, Johnson N. Developments in rabies vaccines. Clin Exp Immunol. 2012;169:199–204. [DOI] [PubMed] [PMC]

22.

Rhee JH. Towards Vaccine 3.0: new era opened in vaccine research and industry. Clin Exp Vaccine Res. 2014;3:1–4. [DOI] [PubMed] [PMC]

23.

Lepenies B, Yin J, Seeberger PH. Applications of synthetic carbohydrates to chemical biology. Curr Opin Chem Biol. 2010;14:404–11. [DOI] [PubMed]

24.

Pardee K, Slomovic S, Nguyen PQ, Lee JW, Donghia N, Burrill D, et al. Portable, on-demand biomolecular manufacturing. Cell. 2016;167:248–59.e12. [DOI] [PubMed]

25.

Kennedy RB, Poland GA. The top five “game changers” in vaccinology: toward rational and directed vaccine development. OMICS. 2011;15:533–7. [DOI] [PubMed] [PMC]

26.

Burton DR. What are the most powerful immunogen design vaccine strategies? Reverse vaccinology 2.0 shows great promise. Cold Spring Harb Perspect Biol. 2017;9:a030262. [DOI] [PubMed] [PMC]

27.

Rappuoli R, Bottomley MJ, D’Oro U, Finco O, De Gregorio E. Reverse vaccinology 2.0: human immunology instructs vaccine antigen design. J Exp Med. 2016;213:469–81. [DOI] [PubMed] [PMC]

28.

Blohmke CJ, O’Connor D, Pollard AJ. The use of systems biology and immunological big data to guide vaccine development. Genome Med. 2015;7:114. [DOI] [PubMed] [PMC]

29.

Horvatić A, Kuleš J, Guillemin N, Galan A, Mrljak V, Bhide M. High-throughput proteomics and the fight against pathogens. Mol Biosyst. 2016;12:2373–84. [DOI] [PubMed]

30.

Dwivedi P, Alam SI, Tomar RS. Secretome, surfome and immunome: emerging approaches for the discovery of new vaccine candidates against bacterial infections. World J Microbiol Biotechnol. 2016;32:155. [DOI] [PubMed]

31.

Poland GA, Ovsyannikova IG, Kennedy RB, Haralambieva IH, Jacobson RM. Vaccinomics and a new paradigm for the development of preventive vaccines against viral infections. OMICS. 2011;15:625–36. [DOI] [PubMed] [PMC]

32.

Davies MN, Flower DR. Harnessing bioinformatics to discover new vaccines. Drug Discov Today. 2007;12:389–95. [DOI] [PubMed]

33.

Lew-Tabor AE, Rodriguez Valle M. Erratum to “A review of reverse vaccinology approaches for the development of vaccines against ticks and tick borne diseases” [Ticks Tick-borne Dis. 7 (4) (2016) 573–585]. Ticks Tick Borne Dis. 2016;7:1236–7. Erratum for: Ticks Tick Borne Dis. 2016;7:573–85. [DOI] [PubMed]

34.

de la Fuente J, Merino O. Vaccinomics, the new road to tick vaccines. Vaccine. 2013;31:5923–9. [DOI] [PubMed]

35.

Prudencio CR, Nascimento R, Filho MM, Marra Ade O, de Souza GR, Almeida JF, et al. In silico analysis for identification of tick phagotopes selected by phage-displayed libraries. Rev Bras Parasitol Vet. 2009;18:39–41. [DOI] [PubMed]

36.

Nijhof AM, Balk JA, Postigo M, Jongejan F. Selection of reference genes for quantitative RT-PCR studies in Rhipicephalus (Boophilus) microplus and Rhipicephalus appendiculatus ticks and determination of the expression profile of Bm86. BMC Mol Biol. 2009;10:112. [DOI] [PubMed] [PMC]

37.

Andreotti R, Pedroso MS, Caetano AR, Martins NF. Comparison of predicted binders in Rhipicephalus (Boophilus) microplus intestine protein variants Bm86 Campo Grande strain, Bm86 and Bm95. Rev Bras Parasitol Vet. 2008;17:93–8. [DOI] [PubMed]

38.

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] [PubMed] [PMC]

39.

Willadsen P. The molecular revolution in the development of vaccines against ectoparasites. Vet Parasitol. 2001;101:353–68. [DOI] [PubMed]

40.

Graf JF, Gogolewski R, Leach-Bing N, Sabatini GA, Molento MB, Bordin EL, et al. Tick control: an industry point of view. Parasitology. 2004;129:S427–42. [DOI] [PubMed]

41.

Kay BH, Kemp DH. Vaccines against arthropods. Am J Trop Med Hyg. 1994;50:87–96. [DOI] [PubMed]

42.

Willadsen P. Antigen cocktails: valid hypothesis or unsubstantiated hope? Trends Parasitol. 2008;24:164–7. [DOI] [PubMed]

43.

Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021;21:83–100. Erratum in: Nat Rev Immunol. 2021;21:129. [DOI] [PubMed] [PMC]

44.

Mulenga A, Sugimoto C, Onuma M. Issues in tick vaccine development: identification and characterization of potential candidate vaccine antigens. Microbes Infect. 2000;2:1353–61. [DOI] [PubMed]

45.

Willadsen P. Anti-tick vaccines. Parasitology. 2004;129:S367–87. [DOI] [PubMed]

46.

Willadsen P. Tick control: thoughts on a research agenda. Vet Parasitol. 2006;138:161–8. [DOI] [PubMed]

47.

Nuttall PA, Trimnell AR, Kazimirova M, Labuda M. Exposed and concealed antigens as vaccine targets for controlling ticks and tick-borne diseases. Parasite Immunol. 2006;28:155–63. [DOI] [PubMed]

48.

de la Fuente J, Almazán C, Canales M, Pérez de la Lastra JM, Kocan KM, Willadsen P. A ten-year review of commercial vaccine performance for control of tick infestations on cattle. Anim Health Res Rev. 2007;8:23–8. [DOI] [PubMed]

49.

Canales M, Moreno-Cid JA, Almazán C, Villar M, de la Fuente J. Bioprocess design and economics of recombinant Bm86/Bm95 antigen production for anti-tick vaccines. Biochem Eng J. 2010;52:79–90. [DOI]

50.

Odongo D, Kamau L, Skilton R, Mwaura S, Nitsch C, Musoke A, et al. Vaccination of cattle with TickGARD induces cross-reactive antibodies binding to conserved linear peptides of Bm86 homologues in Boophilus decoloratus. Vaccine. 2007;25:1287–96. [DOI] [PubMed]

51.

Vargas M, Montero C, Sánchez D, Pérez D, Valdés M, Alfonso A, et al. Two initial vaccinations with the Bm86-based Gavac^plus vaccine against Rhipicephalus (Boophilus) microplus induce similar reproductive suppression to three initial vaccinations under production conditions. BMC Vet Res. 2010;6:43. [DOI] [PubMed] [PMC]

52.

De La Fuente J, Rodríguez M, García-García JC. Immunological control of ticks through vaccination with Boophilus microplus gut antigens. Ann N Y Acad Sci. 2000;916:617–21. [DOI] [PubMed]

53.

Canales M, de la Lastra JMP, Naranjo V, Nijhof AM, Hope M, Jongejan F, et al. Expression of recombinant Rhipicephalus (Boophilus) microplus, R. annulatus and R. decoloratus Bm86 orthologs as secreted proteins in Pichia pastoris. BMC Biotechnol. 2008;8:14. [DOI] [PubMed] [PMC]

54.

Kopp N, Diaz D, Amacker M, Odongo DO, Beier K, Nitsch C, et al. Identification of a synthetic peptide inducing cross-reactive antibodies binding to Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) microplus, Hyalomma anatolicum anatolicum and Rhipicephalus appendiculatus BM86 homologues. Vaccine. 2009;28:261–9. [DOI] [PubMed]

55.

Canales M, Almazán C, Naranjo V, Jongejan F, de la Fuente J. Vaccination with recombinant Boophilus annulatus Bm86 ortholog protein, Ba86, protects cattle against B. annulatus and B. microplus infestations. BMC Biotechnol. 2009;9:29. [DOI] [PubMed] [PMC]

56.

Willadsen P, Kemp DH. Vaccination with ‘concealed’ antigens for tick control. Parasitol Today.1988;4:196–8. [DOI] [PubMed]

57.

García-García JC, Montero C, Redondo M, Vargas M, Canales M, Boue O, et al. Control of ticks resistant to immunization with Bm86 in cattle vaccinated with the recombinant antigen Bm95 isolated from the cattle tick, Boophilus microplus. Vaccine. 2000;18:2275–87. [DOI] [PubMed]

58.

Almazán C, Kocan KM, Bergman DK, Garcia-Garcia JC, Blouin EF, de la Fuente J. Characterization of genes transcribed in an Ixodes scapularis cell line that were identified by expression library immunization and analysis of expressed sequence tags. Gene Ther Mol Biol. 2003;7:43–59.

59.

Canales M, Naranjo V, Almazán C, Molina R, Tsuruta SA, Szabó MPJ, et al. Conservation and immunogenicity of the mosquito ortholog of the tick-protective antigen, subolesin. Parasitol Res. 2009;105:97–111. [DOI] [PubMed]

60.

Aljamali MN, Ramakrishnan VG, Weng H, Tucker JS, Sauer JR, Essenberg RC. Microarray analysis of gene expression changes in feeding female and male lone star ticks, Amblyomma americanum (L). Arch Insect Biochem Physiol. 2009;71:236–53. [DOI] [PubMed] [PMC]

61.

Aljamali MN, Hern L, Kupfer D, Downard S, So S, Roe BA, et al. Transcriptome analysis of the salivary glands of the female tick Amblyomma americanum (Acari: Ixodidae). Insect Mol Biol. 2009;18:129–54. [DOI] [PubMed]

62.

Bior AD, Essenberg RC, Sauer JR. Comparison of differentially expressed genes in the salivary glands of male ticks, Amblyomma americanum and Dermacentor andersoni. Insect Biochem Mol Biol. 2002;32:645–55. [DOI] [PubMed]

63.

Valenzuela JG, Francischetti IMB, Pham VM, Garfield MK, Mather TN, Ribeiro JMC. Exploring the sialome of the tick Ixodes scapularis. J Exp Biol. 2002;205:2843–64. [DOI] [PubMed]

64.

Guilfoile PG, Packila M. Identification of four genes expressed by feeding female Ixodes scapularis, including three with sequence similarity to previously recognized genes. Exp Appl Acarol. 2004;32:103–10. [DOI] [PubMed]

65.

Schwarz A, von Reumont BM, Erhart J, Chagas AC, Ribeiro JMC, Kotsyfakis M. De novo Ixodes ricinus salivary gland transcriptome analysis using two next-generation sequencing methodologies. FASEB J. 2013;27:4745–56. [DOI] [PubMed] [PMC]

66.

Mudenda L, Pierlé SA, Turse JE, Scoles GA, Purvine SO, Nicora CD, et al. Proteomics informed by transcriptomics identifies novel secreted proteins in Dermacentor andersoni saliva. Int J Parasitol. 2014;44:1029–37. [DOI] [PubMed]

67.

de Castro MH, de Klerk D, Pienaar R, Latif AA, Rees DJG, Mans BJ. De novo assembly and annotation of the salivary gland transcriptome of Rhipicephalus appendiculatus male and female ticks during blood feeding. Ticks Tick Borne Dis. 2016;7:536–48. [DOI] [PubMed]

68.

Heekin AM, Guerrero FD, Bendele KG, Saldivar L, Scoles GA, Gondro C, et al. Analysis of Babesia bovis infection-induced gene expression changes in larvae from the cattle tick, Rhipicephalus (Boophilus) microplus. Parasit Vectors. 2012;5:162. [DOI] [PubMed] [PMC]

69.

Guerrero FD, Miller RJ, Rousseau ME, Sunkara S, Quackenbush J, Lee Y, et al. BmiGI: a database of cDNAs expressed in Boophilus microplus, the tropical/southern cattle tick. Insect Biochem Mol Biol. 2005;35:585–95. [DOI] [PubMed]

70.

Guerrero FD, Bendele KG, Chen AC, Li AY, Miller RJ, Pleasance E, et al. Serial analysis of gene expression in the southern cattle tick following acaricide treatment of larvae from organophosphate resistant and susceptible strains. Insect Mol Biol. 2007;16:49–60. [DOI] [PubMed]

71.

Wang M, Guerrero FD, Pertea G, Nene VM. Global comparative analysis of ESTs from the southern cattle tick, Rhipicephalus (Boophilus) microplus. BMC Genomics. 2007;8:368. [DOI] [PubMed] [PMC]

72.

Saldivar L, Guerrero FD, Miller RJ, Bendele KG, Gondro C, Brayton KA. Microarray analysis of acaricide-inducible gene expression in the southern cattle tick, Rhipicephalus (Boophilus) microplus. Insect Mol Biol. 2008;17:597–606. [DOI] [PubMed]

73.

Heekin AM, Guerrero FD, Bendele KG, Saldivar L, Scoles GA, Dowd SE, et al. Gut transcriptome of replete adult female cattle ticks, Rhipicephalus (Boophilus) microplus, feeding upon a Babesia bovis-infected bovine host. Parasitol Res. 2013;112:3075–90. [DOI] [PubMed]

74.

Heekin AM, Guerrero FD, Bendele KG, Saldivar L, Scoles GA, Dowd SE, et al. The ovarian transcriptome of the cattle tick, Rhipicephalus (Boophilus) microplus, feeding upon a bovine host infected with Babesia bovis. Parasit Vectors. 2013;6:276. [DOI] [PubMed] [PMC]

75.

Guerrero FD, Kellogg A, Ogrey AN, Heekin AM, Barrero R, Bellgard MI, et al. Prediction of G protein-coupled receptor encoding sequences from the synganglion transcriptome of the cattle tick, Rhipicephalus microplus. Ticks Tick Borne Dis. 2016;7:670–7. [DOI] [PubMed] [PMC]

76.

Mulenga A, Sugimoto C, Sako Y, Ohashi K, Musoke A, Shubash M, et al. Molecular characterization of a Haemaphysalis longicornis tick salivary gland-associated 29-kilodalton protein and its effect as a vaccine against tick infestation in rabbits. Infect Immun. 1999;67:1652–8. [DOI] [PubMed] [PMC]

77.

de la Fuente J, Kocan KM. Advances in the identification and characterization of protective antigens for recombinant vaccines against tick infestations. Expert Rev Vaccines. 2003;2:583–93. [DOI] [PubMed]

78.

Zivkovic Z, Esteves E, Almazán C, Daffre S, Nijhof AM, Kocan KM, et al. Differential expression of genes in salivary glands of male Rhipicephalus (Boophilus)microplus in response to infection with Anaplasma marginale. BMC Genomics. 2010;11:186. [DOI] [PubMed] [PMC]

79.

Maruyama SR, Garcia GR, Teixeira FR, Brandão LG, Anderson JM, Ribeiro JMC, et al. Mining a differential sialotranscriptome of Rhipicephalus microplus guides antigen discovery to formulate a vaccine that reduces tick infestations. Parasit Vectors. 2017;10:206. [DOI] [PubMed] [PMC]

80.

Wang H, Nuttall PA. Immunoglobulin-binding proteins in ticks: new target for vaccine development against a blood-feeding parasite. Cell Mol Life Sci. 1999;56:286–95. [DOI] [PubMed]

81.

Elvin CM, Kemp DH. Generic approaches to obtaining efficacious antigens from vector arthropods. Int J Parasitol. 1994;24:67–79. [DOI] [PubMed]