medigraphic.com
Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán

2020, Number 3

<< Back

Rev Biomed 2020; 31 (3)

Bacteriophages as vaccine delivery system

Ramírez-Pereda N, Regalado-Santiago C, Cruz-Sánchez JJ, Rodríguez-Cortés O, González-Cano P

Language: Spanish
References: 107
Page: 159-172
PDF size: 497.68 Kb.


ABSTRACT

Introduction. Throughout history, diff erent vaccines have been designed based on the recognition of epitopes present in the vaccine antigens. However, despite the advances and achievements in vaccinology, to date it has not been possible to develop effi cient vaccines against pathogens like the Human Immunodefi ciency Virus due to its antigenic complexity. On the other hand, in the last two decades multiple emerging infectious diseases like infl uenza and the appearance of zika and chikungunya viruses have arisen in the last two decades. Therefore, there is a need for the rational development of new and effi cient vaccines that are stable, safe, able to induce a cellular and humoral immune response, and at the same time working as eff ective vaccine adjuvants to fi ght infectious diseases.
Objective. Thus, the objective of this review is to exalt the importance of tools like Next Generation Sequencing coupled to reverse vaccinology to identify new vaccine epitopes on infected tissue and expressing them on bacteriophages to design an immunoprotective vaccine which is cheap to produce, safe, stable, and can be administrated without adjuvant.
Methodology. This review was performed with a systematic literature search on the PubMed database related to each topic.


REFERENCES

  1. Clem AS. Fundamentals of Vaccine Immunology. J Global Infect Dis. 2011 Jan-Mar. 3(1): 73-8. doi:10.4103/0974- 777x.77299.

  2. Greenwood B. The contribution of vaccination to global health: past, present and future. Philos Trans R Soc Lond B Biol Sci. 2014 May; 369(1645):20130433. doi: 10.1098/rstb.2013.0433.

  3. Pastoret PP and Jones P. Veterinary vaccines for animal and public health. Dev Biol (Basel). 2004; 119:15-29. PMID: 15742615.

  4. Paul-Pierre P. Emerging diseases, zoonoses and vaccines to control them. Vaccine. 2009 Jun. 27(46):6435-38. doi: 10.1016/j.vaccine.2009.06.021.

  5. Mayr A. [Vaccination of animals and human health]. Zentralbl Bakteriol Mikrobiol Hyg B. 1985 Feb; 180(2- 3): 175-89. German. PMID: 2986381

  6. Goulart LR and de S. Santos P. Strategies for Vaccine Design Using Phage Display-Derived Peptides, in Vaccine Design: Methods and Protocols, Volume 2: Vaccines for Veterinary Diseases. S. Thomas, Editor. 2016, Springer New York: New York, NY. p. 423-435.

  7. Wadia J, Eguch A and Dowdy SF. DNA delivery into mammalian cells using bacteriophage lambda displaying the TAT transduction domain. Cold Spring Harb Protoc. 2013 (1). doi:10.1101/pdb.prot072660.

  8. Aghebati Maleki L, Bakhshineja B, Baradaran B, Motallebnezhad M, Aghebati Maleki A, Nickho H., et al., Phage display as a promising approach for vaccine development. J Biomed Sci. 2016 Sep; 23(1): 66. doi:10.1186/s12929-016-0285-9.

  9. Gorski A, Miedzybrodzki R, Jonczyk-Matysiak E, Zaczek M and Borysowski J. Phage-specific diverse effects of bacterial viruses on the immune system. Future Microbiol. 2019 Sep; 14(14):1171-74. doi: 10.2217/ fmb-2019-0222

  10. Gaubin M, Fanutti C, Mishal Z, Durrbach A, De Berardinis P, Sartorius R., et al. Processing of filamentous bacteriophage virions in antigen-presenting cells targets both HLA class I and class II peptide loading compartments. DNA and Cell Biology. 2003 Jan; 22(1):11-18. doi: 10.1089/104454903321112451

  11. Slutter B and Jiskoot W. Sizing the optimal dimensions of a vaccine delivery system: a particulate matter. Expert Opin Drug Deliv. 2016. 13(2): 167-70. doi:10.1517/174 25247.2016.1121989.

  12. Kulkarni-Kale U, Bhosle S and Kolaskar AS. CEP: a conformational epitope prediction server. Nucleic Acids Res. 2005. 33 (Web Server issue): W168-171. doi:33/ suppl_2/W168 [pii]10.1093/nar/gki460.

  13. Rinaudo CD, Telford JL, Rappuoli R and Seib KL. Vaccinology in the genome era. J Clin Invest. 2009. 119(9): 2515-25. doi:38330 [pii]10.1172/ JCI38330.

  14. Baxter D. Active and passive immunity, vaccine types, excipients and licensing. Occup Med (Lond). 2007 Dec; 57(8): 552-56. doi:10.1093/occmed/kqm110.

  15. Rollenhagen C. Sorensen M, Rizos K, Hurvitz R and Bumann D. Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen. Proc Natl Acad Sci. 2004 Jun; 101(23): p. 8739-44. doi: 10.1073/pnas.0401283101[pii].

  16. Prachi P, Donati C, Masciopinto F, Rappuoli R and Bagnoli F. Deep sequencing in pre- and clinical vaccine research. Public Health Genomics. 2013;16(1-2):62-8. doi: 10.1159/000345611. Epub 2013 Mar 18. PMID: 23548719.

  17. Kool M, Fierens K and Lambrecht BN. Alum adjuvant: some of the tricks of the oldest adjuvant. J Med Microbiol. 2012. 61(7):927-34. doi:10.1099/ jmm.0.038943-0.

  18. Lauring AS, Jones JO and Andino R. Rationalizing the development of live attenuated virus vaccines. Nat Biotechnol. 2010 Jun; 28(6):573-79. doi: 10.1038/ nbt.1635.

  19. Lin IY, Van TT and Smooker PM. Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery. Vaccines (Basel). 2015. 3(4): 940-72. doi: 10.3390/vaccines3040940.

  20. Hanley KA. The double-edged sword: How evolution can make or break a live-attenuated virus vaccine. Evolution. 2012 Dec; 4(4):635-43. doi:10.1007/s12052011-0365-y.

  21. Plotkin S. History of vaccination. Proc Natl Acad Sci. 2014 Aug; 111(34): 12283-87 doi: 10.1073/ pnas.1400472111.

  22. Patronov A and Doytchinova I. T-cell epitope vaccine design by immunoinformatics. Open Biology. 2013 Jun; 3(1):120139. doi:10.1098/rsob.120139.

  23. Arvas A. Vaccination in patients with immunosuppression. Turk Pediatri Ars. 2014 Sep; 49(3): 181-5. doi: 10.5152/ tpa.2014.2206

  24. Sridhar S, Brokstad KA and Cox RJ. Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines. Vaccines. 2015 Apr; 3(2):373-89. doi:10.3390/vaccines3020373.

  25. Stauffer F, El-Bacha T, Da Poian AT Advances in the Development of Inactivated Virus Vaccines. In Recent Patents on Anti-Infective Drug Discovery. 2006. 1(3): 291-6. doi:10.2174/157489106778777673.

  26. Kotloff KL, Wasserman SS, Losonsky GA, Thomas Jr W, Nichols R, Edelman R., et al., Safety and Immunogenicity of Increasing Doses of a Clostridium difficile Toxoid Vaccine Administered to Healthy Adults. Infect Immun. 2001 Feb; 69(2): 988-95. doi:10.1128/ iai.69.2.988-995.2001.

  27. Wilton T, Dunn G, Eastwood D, Minor PD and J. Martin J. Effect of formaldehyde inactivation on poliovirus. J Virol. 2014. Aug; 88(20):11955-64. doi: 10.1128/ jvi.01809-14.

  28. Lipinski T, Fitieh A, St Pierre J, Ostergaard HL, Bundle DR, Touret N. Enhanced immunogenicity of a tricomponent mannan tetanus toxoid conjugate vaccine targeted to dendritic cells via Dectin-1 by incorporating beta-glucan. J Immunol. 2013 Apr; 190(8):4116-28. doi:10.4049/jimmunol.1202937.

  29. Yu R, Fang T, Liu S, Song X, Yu C, Li J, et al. Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys. Toxins (Basel). 2016 Jun; 8(7):194. doi: 10.3390/toxins8070194

  30. Patronov A, Doytchinova I. T-cell epitope vaccine design by immunoinformatics. Open Biol. 2013 Jan; 3(1):120139. doi: 10.1098/rsob.120139

  31. Coban C, Kobiyama K, Jounai N, Tozuka M, Ishii KJ. DNA vaccines: a simple DNA sensing matter? Hum Vaccin Immunother. 2013 Oct; 9(10):2216-21. doi: 10.4161/hv.25893.

  32. Dalpke AH, Heeg K. CpG-DNA as immune response modifier. Int J Med Microbiol. 2004 Oct; 294(5):345-54. doi: 10.1016/j.ijmm. 2004.07.005.

  33. Ferraro B, Morrow MP, Hutnick NA, Shin TH, Lucke CE, Weiner DB. Clinical applications of DNA vaccines: current progress. Clin Infect Dis. 2011 Aug;53(3):296- 302. doi: 10.1093/cid/cir334.

  34. Harty JT, Bevan MJ. Responses of CD8+ T cells to intracellular bacteria. Curr Opin Immunol. 1999 Jun; 11(1):89-93. doi:10.1016/S0952-7915(99)80016-8.

  35. Liu MA. DNA vaccines: a review. J Intern Med. 2003 Apr; 253(4):402-10. doi: 10.1046/j.1365-2796.2003.01140.x

  36. Khan KH. DNA vaccines: roles against diseases. Germs. 2013 Mar; 3(1):26-35. doi: 10.11599/germs.2013.1034.

  37. Tan M, Jiang, X Recent advancements in combination subunit vaccine development. Hum Vaccin Immunother. 2017 Jan; 13(1):180-5. doi: 10.1080/21645515.2016.1229719.

  38. Moyle PM, Toth I. Modern subunit vaccines: development, components, and research opportunities. Chem Med Chem. 2013 Jan; 8(3):360-76. doi: 10.1002/ cmdc.201200487.

  39. Vartak A, Sucheck SJ. Recent Advances in Subunit Vaccine Carriers. Vaccines (Basel). 2016 Apr;4(2):12. doi: 10.3390/vaccines4020012.

  40. Foged C. Subunit vaccines of the future: the need for safe, customized and optimized particulate delivery systems. Ther Deliv. 2011 Aug; 2(8):1057-77. doi: 10.4155/tde.11.68.

  41. Wang M, Jiang S, Wang Y. Recent advances in the production of recombinant subunit vaccines in Pichia pastoris. Bioengineered. 2016 Apr;7(3):155-65. doi: 10.1080/21655979.2016.1191707

  42. Garcon N, Leroux G, Cheng WF. Vaccine Adjuvants in Understanding Modern Vaccines Perspectives in Vaccinology, 2011 Aug; 89-113. doi.org/10.1016/j. pervac.2011.05.004

  43. Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity. 2010 Oct;33(4):492-503. doi: 10.1016/j.immuni.2010.10.002

  44. Mohan T, Verma P, Rao DN. Novel adjuvants & delivery vehicles for vaccines development: a road ahead. Indian J Med Res. 2013 Nov;138(5):779-95. PMID: 24434331; PMCID: PMC3928709.

  45. Gupta RK, Relyveld EH, Lindblad EB, Bizzini B, Ben- Efraim S, Gupta CK. Adjuvants--a balance between toxicity and adjuvanticity. Vaccine. 1993;11(3):293-306. doi: 10.1016/0264-410x(93)90190-9.

  46. Awate S, Babiuk LA, Mutwiri G. Mechanisms of action of adjuvants. Front Immunol. 2013 May; 4:114. doi: 10.3389/fimmu.2013.00114.

  47. Snapper CM. Distinct Immunologic Properties of Soluble Versus Particulate Antigens. Front Immunol. 2018 Mar; 9:598. doi: 10.3389/fimmu.2018.00598.

  48. O'Hagan DT, Friedland LR, Hanon E, Didierlaurent AM. Towards an evidence based approach for the development of adjuvanted vaccines. Curr Opin Immunol. 2017 Aug; 47:93-102. doi: 10.1016/j.coi.2017.07.010

  49. O'Hagan DT, Ott GS, Nest GV, Rappuoli R, Giudice GD. The history of MF59(®) adjuvant: a phoenix that arose from the ashes. Expert Rev Vaccines. 2013 Jan;12(1):13- 30. doi: 10.1586/erv.12.140.

  50. Burrell LS, Johnston CT, Schulze D, Klein J, White JL, Hem SL. Aluminium phosphate adjuvants prepared by precipitation at constant pH. Part I: composition and structure. Vaccine. 2000 Sep;19(2-3):275-81. doi: 10.1016/s0264-410x(00)00160-2.

  51. Burrell LS, Johnston CT, Schulze D, Klein J, White JL, Hem SL. Aluminium phosphate adjuvants prepared by precipitation at constant pH. Part II: physicochemical properties. Vaccine. 2000 Sep;19(2-3):282-7. doi: 10.1016/s0264-410x(00)00162-6

  52. De Gregorio E, Caproni E, Ulmer JB. Vaccine adjuvants: mode of action. Front Immunol. 2013 Jul;4:214. doi: 10.3389/fimmu.2013.00214

  53. Lambrecht BN, Kool M, Willart MA, Hammad H. Mechanism of action of clinically approved adjuvants. Curr Opin Immunol. 2009 Feb;21(1):23-9. doi: 10.1016/j.coi.2009.01.004

  54. Swanson KV, Deng M,Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019 Apr; 19(8):477- 89. doi: 10.1038/s41577-019-0165-0.

  55. Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013 Jun;13(6):397- 411. doi: 10.1038/nri3452.

  56. Awate S, Wilson HL, Lai K, Babiuk LA, Mutwiri G. Activation of adjuvant core response genes by the novel adjuvant PCEP. Mol Immunol. 2012 Jul;51(3-4):292- 303. doi: 10.1016/j.molimm.2012.03.026.

  57. Schijns VE, Lavelle EC. Trends in vaccine adjuvants. Expert Rev Vaccines. 2011 Apr;10(4):539-50. doi: 10.1586/erv.11.21

  58. Calabro S, Tortoli M, Baudner BC, Pacitto A, Cortese M, O'Hagan DT, et al. Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine. 2011 Feb;29(9):1812-23. doi: 10.1016/j. vaccine.2010.12.090.

  59. Ott G, Barchfeld GL, Chernoff D, Radhakrishnan R, van Hoogevest P, Van Nest G. MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol. 1995;6:277-96. doi: 10.1007/978-1-4615- 1823-5_10.

  60. Seubert A, Monaci E, Pizza M, O'Hagan DT, Wack A. The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol. 2008 Apr;180(8):5402-12. doi: 10.4049/ jimmunol.180.8.5402

  61. Théry C, Amigorena S. The cell biology of antigen presentation in dendritic cells. Curr Opin Immunol. 2001 Feb;13(1):45-51. doi: 10.1016/s0952-7915(00)00180-1.

  62. Andrianov AK, Marin A, Chen J. Synthesis, properties, and biological activity of poly[di(sodium carboxylatoethylphenoxy)phosphazene]. Biomacromolecules. 2006 Jan;7(1):394-9. doi: 10.1021/ bm050790a.

  63. Awate S, Eng NF, Gerdts V, Babiuk LA, Mutwiri G. Caspase-1 Dependent IL-1β Secretion and Antigen- Specific T-Cell Activation by the Novel Adjuvant, PCEP. Vaccines. 2014 Jun;2(3):500-14. doi:10.3390/ vaccines2030500.

  64. Nascimento IP, Leite LC. Recombinant vaccines and the development of new vaccine strategies. Braz J Med Biol Res. 2012 Dec;45(12):1102-11. doi: 10.1590/s0100- 879x2012007500142

  65. González-Cano P, Gamage LNA, Marciniuk K, Hayes C, Napper S, Hayes S, Griebel PJ. Lambda display phage as a mucosal vaccine delivery vehicle for peptide antigens. Vaccine. 2017 Dec;35(52):7256-7263. doi: 10.1016/j. vaccine.2017.11.010

  66. Gamage LN, Ellis J, Hayes S. Immunogenicity of bacteriophage lambda particles displaying porcine Circovirus 2 (PCV2) capsid protein epitopes. Vaccine. 2009 Nov 5;27(47):6595-604. doi: 10.1016/j. vaccine.2009.08.019.

  67. Orlova EV. Bacteriophages and Their Structural organization, in Bacteriphages Ipek Kurtboke, IntechOpen, 2012 Mar; p 3-30. doi: 10.5772/34642.

  68. Wommack KE, Colwell RR. Virioplankton: viruses in aquatic ecosystems. Microbiol Mol Biol Rev. 2000 Mar;64(1):69-114. doi: 10.1128/mmbr.64.1.69- 114.2000.

  69. Haq I.U, Chaudhry WN, Akhtar MN, Andleeb S, Qadri I. Bacteriophages and their implications on future biotechnology: a review. Virol J. 2012 Jan;9(9):1-8. doi: 10.1186/1743-422X-9-9.

  70. Wittebole X, De Roock S, Opal SM. A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence. 2014 Jan;5(1):226-35. doi: 10.4161/viru.25991.

  71. Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985 Jun;228(4705):1315-7. doi: 10.1126/ science.4001944.

  72. Greenwood J, Willis AE, Perham RN. Multiple display of foreign peptides on a filamentous bacteriophage: Peptides from Plasmodium falciparum circumsporozoite protein as antigens. J Mol Biol. 1991 Aug; 220(4): 821- 27. doi: 10.1016/0022-2836(91)90354-9.

  73. Trovato M, Krebs SJ, Haigwood NL, De Berardinis P. Delivery strategies for novel vaccine formulations. World J Virol. 2012 Feb;1(1):4-10. doi: 10.5501/wjv. v1.i1.4.

  74. Sidhu SS. Engineering M13 for phage display. Biomol Eng. 2001 Sep;18(2):57-63. doi: 10.1016/s1389- 0344(01)00087-9

  75. Hashiguchi S, Yamaguchi Y, Takeuchi O, Akira S, Sugimura K. Immunological basis of M13 phage vaccine: Regulation under MyD88 and TLR9 signaling. Biochem Biophys Res Commun. 2010 Nov;402(1):19- 22. doi: 10.1016/j.bbrc.2010.09.094.

  76. Fuh G, Sidhu SS. Efficient phage display of polypeptides fused to the carboxy-terminus of the M13 gene-3 minor coat protein. FEBS Lett. 2000 Sep;480(2-3):231-4. doi: 10.1016/s0014-5793(00)01946-3.

  77. Hashemi H, Bamdad T, Jamali A, Pouyanfard S, Mohammadi MG. Evaluation of humoral and cellular immune responses against HSV-1 using genetic immunization by filamentous phage particles: a comparative approach to conventional DNA vaccine. J Virol Methods. 2010 Feb;163(2):440-4. doi: 10.1016/j. jviromet.2009.11.008.

  78. Molenaar TJ, Michon I, de Haas SA, van Berkel TJ, Kuiper J, Biessen EA. Uptake and processing of modified bacteriophage M13 in mice: implications for phage display. Virology. 2002 Feb;293(1):182-91. doi: 10.1006/viro.2001.1254.

  79. Moon JS, Kim WG, Kim C, Park GT, Heo J, Yoo SY, et al., M13 Bacteriophage-Based Self-Assembly Structures and Their Functional Capabilities. Mini Rev Org Chem. 2015 Jun;12(3):271-81. doi: 10.2174/1570193X120315 0429105418

  80. Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev. 2012 Sep;249(1):158-75. doi: 10.1111/j.1600-065X.2012.01146.x.

  81. Hashiguchi S, Yamaguchi Y, Takeuchi O, Akira S, Sugimura K. Immunological basis of M13 phage vaccine: Regulation under MyD88 and TLR9 signaling. Biochem Biophys Res Commun. 2010 Nov;402(1):19- 22. doi: 10.1016/j.bbrc.2010.09.094

  82. Mora M, Veggi D, Santini L, Pizza M, Rappuoli R. Reverse vaccinology. Drug Discov Today. 2003 Jun; 8(10):459-64. doi: 10.1016/S1359-6446(03)02689-8

  83. Sette A, Rappuoli R. Reverse vaccinology: developing vaccines in the era of genomics. Immunity. 2010 Oct;33(4):530-41. doi: 10.1016/j.immuni.2010.09.017

  84. Rappuoli R. Reverse vaccinology. Curr Opin Microbiol. 2000 Oct;3(5): 445-50. doi: 10.1016/S1369- 5274(00)00119-3

  85. Khalili S, Jahangiri A, Borna H, Ahmadi Zanoos K, Amani J. Computational vaccinology and epitope vaccine design by immunoinformatics. Acta Microbiol Immunol Hung. 2014 Sep;61(3):285-307. doi: 10.1556/ AMicr.61.2014.3.4.

  86. Lo YT, Pai TW, Wu WK, Chang HT. Prediction of conformational epitopes with the use of a knowledgebased energy function and geometrically related neighboring residue characteristics. BMC Bioinformatics. 2013;14 Suppl 4(Suppl 4):S3. doi: 10.1186/1471-2105- 14-S4-S3. Epub 2013 Mar 8.

  87. Flaherty DK. Immunology for Pharmacy, in Immunology for Pharmacy, Elsevier/Mosby, Editor. 2012, Elsevier/ Mosby. p. 23-30.

  88. Michalik M., Djahanshiri B., Leo J.C., Linke D. Reverse Vaccinology: The Pathway from Genomes and Epitope Predictions to Tailored Recombinant Vaccines. In: Thomas S. (eds) Vaccine Design. Methods in Molecular Biology, vol 1403. Humana Press, New York, NY. https:// doi.org/10.1007/978-1-4939-3387-7_4.

  89. La Gruta NL, Gras S, Daley SR, Thomas PG, Rossjohn J. Understanding the drivers of MHC restriction of T cell receptors. Nat Rev Immunol. 2018 Jul;18(7):467-478. doi: 10.1038/s41577-018-0007-5.

  90. Molero-Abraham M, Lafuente EM, Flower DR, Reche PA. Selection of conserved epitopes from hepatitis C virus for pan-populational stimulation of T-cell responses. Clin Dev Immunol. 2013;2013:601943. doi: 10.1155/2013/601943.

  91. Sanchez-Trincado JL, Gomez-Perosanz M, Reche PA. Fundamentals and Methods for T- and B-Cell Epitope Prediction. J Immunol Res. 2017;2017:2680160. doi: 10.1155/2017/2680160. Epub 2017 Dec 28.

  92. Goodswen SJ, Kennedy PJ, Ellis JT. Vacceed: a highthroughput in silico vaccine candidate discovery pipeline for eukaryotic pathogens based on reverse vaccinology. Bioinformatics. 2014 Aug;30(16):2381-3. doi: 10.1093/ bioinformatics/btu300.

  93. Rizwan M, Naz A, Ahmad J, Naz K, Obaid A, Parveen T, Ahsan M, Ali A. VacSol: a high throughput in silico pipeline to predict potential therapeutic targets in prokaryotic pathogens using subtractive reverse vaccinology. BMC Bioinformatics. 2017 Feb;18(1):106. doi: 10.1186/s12859-017-1540-0.

  94. De Groot AS, Berzofsky JA. From genome to vaccine- -new immunoinformatics tools for vaccine design. Methods. 2004 Dec;34(4):425-8. doi: 10.1016/j. ymeth.2004.06.004

  95. Resource, I.E.D.A. IEDB. 2020; Available from: http:// tools.iedb.org/main/.

  96. ProInmune. 2020; Available from: https://www. proimmune.com/.

  97. EpiVax. Epivax. 2020; Available from: https://epivax. com/.

  98. De Groot AS, Martin W. Reducing risk, improving outcomes: bioengineering less immunogenic protein therapeutics. Clin Immunol. 2009 May;131(2):189-201. doi: 10.1016/j.clim.2009.01.009.

  99. Moise L, Gutierrez A, Kibria F, Martin R, Tassone R, Liu R, Terry F, Martin B, De Groot AS. iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines. Hum Vaccin Immunother. 2015;11(9):2312-21. doi: 10.1080/21645515.2015.1061159.

  100. Schönbach C, Ranganathan S, Brusic V. Immunoinformatics. 2007: Springer New York, NY. e-ISBN 978-0-387-72968-8

  101. Moise L, Gutierrez AH, Bailey-Kellogg C, Terry F, Leng Q, Abdel Hady KM, et al. The two-faced T cell epitope: examining the host-microbe interface with JanusMatrix. Hum Vaccin Immunother. 2013 Jul;9(7):1577-86. doi: 10.4161/hv.24615.

  102. De Groot AS, Bishop EA, Khan B, Lally M, Marcon L, Franco J, et al. Engineering immunogenic consensus T helper epitopes for a cross-clade HIV vaccine. Methods. 2004 Dec;34(4):476-87. doi: 10.1016/j. ymeth.2004.06.003.

  103. Buermans HP, den Dunnen JT. Next generation sequencing technology: Advances and applications. Biochim Biophys Acta. 2014 Oct;1842(10):1932-1941. doi: 10.1016/j.bbadis.2014.06.015.

  104. Azhikina T, Skvortsov T, Radaeva T, Mardanov A, Ravin N, Apt A, Sverdlov E. A new technique for obtaining whole pathogen transcriptomes from infected host tissues. Biotechniques. 2010 Feb;48(2):139-44. doi: 10.2144/000113350.

  105. akala SL, Plowe CV. Genetic diversity and malaria vaccine design, testing and efficacy: preventing and overcoming 'vaccine resistant malaria'. Parasite Immunol. 2009 Sep;31(9):560-73. doi: 10.1111/j.1365- 3024.2009.01138.x.

  106. Luciani F. High-throughput sequencing and vaccine design. Rev Sci Tech. 2016 Apr;35(1):53-65. doi: 10.20506/rst.35.1.2417.

  107. Zhao L, Zhang M, Cong H. Advances in the study of HLA-restricted epitope vaccines. Hum Vaccin Immunother, 2013 Aug; 9(12):2566-77. doi: 10.4161/ hv.26088.




2020     |     www.medigraphic.com