Advertisement

Planta

, Volume 245, Issue 5, pp 875–888 | Cite as

Corn-based vaccines: current status and prospects

  • Sergio Rosales-MendozaEmail author
  • Cristhian Sández-Robledo
  • Bernardo Bañuelos-Hernández
  • Carlos Angulo
Review

Abstract

Main conclusion

Corn is an attractive host for vaccine production and oral delivery. The present review provides the current outlook and perspectives for this field.

Among seed-crops, corn represents a key source of biomass for food, fuel production, and other applications. Since the beginning of the development of plant-based vaccines, corn was explored for the production and delivery of vaccines. About a dozen of pathogens have been studied under this technology with distinct degrees of development. A vaccine prototype against enterotoxigenic Escherichia coli was evaluated in a phase I clinical trial and several candidates targeting bacterial and viral diseases are under preclinical evaluation. The present review provides an updated outlook on this topic highlighting the employed expression strategies; perspectives for the field are also provided.

Keywords

Zea mays Maize Seed Vaccine Molecular farming Oral immunization Gamma zein promoter Vacuole targeting 

Notes

Acknowledgements

Current investigations from the group are supported by CONACYT/México (Grant CB-2008-01, 102109 to SRM and Grant CB-2010-01, 151818 to CA) and FAI/UASLP/2014 to SRM.

Compliance with ethical standards

Conflict of interest

None.

References

  1. Aswathy RG, Sivakumar B, Brahatheeswaran D, Fukuda T, Yoshida Y, Maekawa T, Kumar DS (2012) Biocompatible fluorescent zein nanoparticles for simultaneous bioimaging and drug delivery application. Adv Nat Sci Nanosci Nanotechnol 3:025006CrossRefGoogle Scholar
  2. Beck TR, Bernstein H, Mathiowitz E, Morrel E, Schwaller K (1997) Protein microspheres and methods of using them. Google Patents. http://www.google.co.in/patents/US5679377
  3. Boothe JG, Saponja JA, Parmenter DL (1997) Molecular farming in plants: oilseeds as vehicles for the production of pharmaceutical proteins. Drug Dev Res 42:172–181CrossRefGoogle Scholar
  4. Brubacher T (2002) Dry corn milling: an introduction. Tech Bull Int Assoc Oper Millers 2002:7857–7860Google Scholar
  5. Chikwamba R, Cunnick J, Hathaway D, McMurray J, Mason H, Wang K (2002a) A functional antigen in a practical crop: LT-B producing maize protects mice against Escherichia coli heat labile enterotoxin (LT) and cholera (CT). Transgenic Res 11:479–493CrossRefPubMedGoogle Scholar
  6. Chikwamba R, McMurray J, Shou H, Frame B, Pegg SE, Scott P, Mason H, Wang K (2002b) Expression of a synthetic E. coli heat-labile enterotoxin B sub-unit (LT-B) in maize. Mol Breed 10:253–265CrossRefGoogle Scholar
  7. Chikwamba RK, Scott MP, Mejía LB, Mason HS, Wang K (2003) Localization of a bacterial protein in starch granules of transgenic maize kernels. Proc Natl Acad Sci USA 100(19):11127–11132CrossRefPubMedPubMedCentralGoogle Scholar
  8. Czyż M, Dembczyński R, Marecik R, Wojas-Turek J, Milczarek M, Pajtasz-Piasecka E, Wietrzyk J, Pniewski T (2014) Freeze-drying of plant tissue containing HBV surface antigen for the oral vaccine against hepatitis B. Biomed Res Int 2014:485689PubMedPubMedCentralGoogle Scholar
  9. Daniell H, Streatfield SJ, Wycoff K (2001) Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci 6:219–226CrossRefPubMedGoogle Scholar
  10. Daniell H, Chan HT, Pasoreck EK (2016) Vaccination via chloroplast genetics: affordable protein drugs for the prevention and treatment of inherited or infectious human diseases. Annu Rev Genet 50:595–618CrossRefPubMedGoogle Scholar
  11. D’Aoust MA, Couture MM, Charland N, Trépanier S, Landry N, Ors F, Vézina LP (2010) The production of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe response to pandemic influenza. Plant Biotechnol J 8(5):607–619CrossRefPubMedGoogle Scholar
  12. Deckers HM, van Rooijen G, Boothe J, Goll J, Moloney MM, Schryvers AB, Alcantara J, Hutchins WA (2014) Immunogenic formulations comprising oil bodies. US Patent 6761914 B2Google Scholar
  13. Fedorowicz-Strońska O, Kapusta J, Czyż M, Kaczmarek M, Pniewski T (2016) Immunogenicity of parenterally delivered plant-derived small and medium surface antigens of hepatitis B virus. Plant Cell Rep 35(5):1209–1212CrossRefPubMedPubMedCentralGoogle Scholar
  14. Fischer R, Stoger E, Schillberg S, Christou P, Twyman RM (2004) Plant-based production of biopharmaceuticals. Curr Opin Plant Biol 7:152–158CrossRefPubMedGoogle Scholar
  15. Garg R, Tolbert M, Oakes JL, Clemente TE, Bost KL, Piller KJ (2007) Chloroplast targeting of FanC, the major antigenic subunit of Escherichia coli K99 fimbriae, in transgenic soybean. Plant Cell Rep 26:1011–1023CrossRefPubMedGoogle Scholar
  16. Gleba Y, Klimyuk V, Marillonnet S (2007) Viral vectors for the expression of proteins in plants. Curr Opin Biotechnol 18:134–141CrossRefPubMedGoogle Scholar
  17. Gong SJ, Sun SX, Sun QS, Wang JY, Liu XM, Liu GY (2011) Tablets based on compressed zein microspheres for sustained oral administration: design, pharmacokinetics, and clinical study. J Biomater Appl 26:195–208CrossRefPubMedGoogle Scholar
  18. Govea-Alonso DO, Rybicki E, Rosales-Mendoza S (2014) Plant-based vaccines as a global vaccination approach: current perspectives. In: Mendoza SR (ed) Genetically engineered plants as a source of vaccines against wide spread diseases—an integrated view. Springer Science + Business Media, New YorkGoogle Scholar
  19. Guerrero-Andrade O, Loza-Rubio E, Olivera-Flores T, Fehérvári-Bone T, Gómez-Lim MA (2006) Expression of the Newcastle disease virus fusion protein in transgenic maize and immunological studies. Transgenic Res 15(4):455–463CrossRefPubMedGoogle Scholar
  20. Gwirtz JA, Garcia-Casal MN (2014) Processing maize flour and corn meal food products. Ann N Y Acad Sci 1312:66–75CrossRefPubMedGoogle Scholar
  21. Hayden CA, Streatfield SJ, Lamphear BJ, Fake GM, Keener TK, Walker JH, Clements JD, Turner DD, Tizard IR, Howard JA (2012) Bioencapsulation of the hepatitis B surface antigen and its use as an effective oral immunogen. Vaccine 30(19):2937–2942CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hayden CA, Egelkrout EM, Moscoso AM, Enrique C, Keener TK, Jimenez-Flores R, Wong JC, Howard JA (2013) Production of highly concentrated, heat-stable hepatitis B surface antigen in maize. Plant Biotechnol J 10(8):979–984CrossRefGoogle Scholar
  23. Hayden CA, Smith EM, Turner DD, Keener TK, Wong JC, Walker JH, Tizard IR, Jimenez-Flores R, Howard JA (2014) Supercritical fluid extraction provides enhancement to the immune response for orally-delivered hepatitis B surface antigen. Vaccine 31(11):1240–1246CrossRefGoogle Scholar
  24. Hayden CA, Fischer ME, Andrews BL, Chilton HC, Turner DD, Walker JH, Tizard IR, Howard JA (2015) Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses. Vaccine 33:2881–2886CrossRefPubMedPubMedCentralGoogle Scholar
  25. Hemming AW, Berumen J, Mekeel K (2016) Hepatitis B and hepatocellular carcinoma. Clin Liver Dis 20(4):703–720CrossRefPubMedGoogle Scholar
  26. Hickman RA, Faustin A, Wisniewski T (2016) Alzheimer disease and its growing epidemic: risk factors, biomarkers, and the urgent need for therapeutics. Neurol Clin 34(4):941–953CrossRefPubMedGoogle Scholar
  27. Hood EE, Kusnadi A, Nikolov Z, Howard JA (1999) Molecular farming of industrial proteins from transgenic maize. Adv Exp Med Biol 464:127–147CrossRefPubMedGoogle Scholar
  28. Hu J, Ni Y, Dryman BA, Meng XJ, Zhang C (2012) Immunogenicity study of plant-made oral subunit vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). Vaccine 30(12):2068–2074CrossRefPubMedGoogle Scholar
  29. Huang TK, McDonald KA (2012) Bioreactor systems for in vitro production of foreign proteins using plant cell cultures. Biotechnol Adv 30(2):398–409CrossRefPubMedGoogle Scholar
  30. Hurtado-López P, Murdan S (2006) Zein microspheres as drug/antigen carriers: a study of their degradation and erosion, in the presence and absence of enzymes. J Microencapsul 23:303–314CrossRefPubMedGoogle Scholar
  31. Karaman S (2006) Production of vaccines and vaccine components in corn. PhD Thesis, Iowa State UniversityGoogle Scholar
  32. Karaman S, Cunnick J, Wang K (2006) Analysis of immune response in young and aged mice vaccinated with corn-derived antigen against Escherichia coli heat-labile enterotoxin. Mol Biotech 32(1):31–42CrossRefGoogle Scholar
  33. Karaman S, Cunnick J, Wang K (2012) Expression of the cholera toxin B subunit (CT-B) in maize seeds and a combined mucosal treatment against cholera and traveler’s diarrhea. Plant Cell Rep 31:527–537CrossRefPubMedGoogle Scholar
  34. Karg SR, Kallio PT (2009) The production of biopharmaceuticals in plant systems. Biotechnol Adv 27:879–894CrossRefPubMedGoogle Scholar
  35. Kashima K, Yuki Y, Mejima M, Kurokawa S, Suzuki Y, Minakawa S, Takeyama N, Fukuyama Y, Azegami T, Tanimoto T, Kuroda M, Tamura M, Gomi Y, Kiyono H (2016) Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants. Plant Cell Rep 35(3):667–679CrossRefPubMedGoogle Scholar
  36. Keese P (2008) Risks from GMOs due to horizontal gene transfer. Environ Biosafety Res 7(3):123–149CrossRefPubMedGoogle Scholar
  37. Kim HA, Yoo HS, Yang MS, Kwon SY, Kim JS, Choi PS (2010) The development of transgenic maize expressing Actinobacillus pleuropneumoniae ApxIIA gene using Agrobacterium. J Plant Biotechnol 37:313–318CrossRefGoogle Scholar
  38. Kopic S, Geibel JP (2010) Toxin mediated diarrhea in the 21 century: the pathophysiology of intestinal ion transport in the course of ETEC, V. cholerae and rotavirus infection. Toxins (Basel) 2(8):2132–2157CrossRefGoogle Scholar
  39. Kosaki H, Wolt JD, Wang K, Coats JR (2008) Subacute effects of maize-expressed vaccine protein, Escherichia coli heat-labile enterotoxin subunit B (LTB), on the springtail, Folsomia candida, and the earthworm, Eisenia fetida. J Agric Food Chem 56:11342–11347CrossRefPubMedGoogle Scholar
  40. Lakshmi PS, Verma D, Yang X, Lloyd B, Daniell H (2013) Low cost tuberculosis vaccine antigens in capsules: expression in chloroplasts, bio-encapsulation, stability and functional evaluation in vitro. PLoS One 8(1):e54708CrossRefPubMedPubMedCentralGoogle Scholar
  41. Lamphear BJ, Streatfield SJ, Jilka JM, Brooks CA, Barker DK, Turner DD, Delaney DE, Garcia M, Wiggins B, Woodard SL, Hood EE, Tizard IR, Lawhorn B, Howard JA (2002) Delivery of subunit vaccines in maize seed. J Control Release 85:169–180CrossRefPubMedGoogle Scholar
  42. Lamphear BJ, Jilka JM, Kesl L, Welter M, Howard JA, Streatfield SJ (2004) A corn-based delivery system for animal vaccines: an oral transmissible gastroenteritis virus vaccine boosts lactogenic immunity in swine. Vaccine 22:2420–2424CrossRefPubMedGoogle Scholar
  43. Lau O, Ng D, Chan W, Chang S, Sun S (2010) Production of the 42-kDa fragment of Plasmodium falciparum merozoite surface protein 1, a leading malaria vaccine antigen, in Arabidopsis thaliana seeds. Plant Biotechnol J 8:994–1004CrossRefPubMedGoogle Scholar
  44. Lee S, Alwahab NS, Moazzam ZM (2013) Zein-based oral drug delivery system targeting activated macrophages. Int J Pharm 454:388–393CrossRefPubMedGoogle Scholar
  45. Liu C, Yao W, Zhang L, Qian H, Wu W, Jiang X (2010) Cell-penetrating hollow spheres based on milk protein. Chem Commun (Camb) 46:7566–7568CrossRefGoogle Scholar
  46. Loza-Rubio E, Rojas-Anaya E, López J, Olivera-Flores MT, Gómez-Lim MA, Tapia-Perez G (2012) Induction of a protective immune response to rabies virus in sheep after oral immunization with transgenic maize, expressing the rabies virus glycoprotein. Vaccine 30(37):5551–5556CrossRefPubMedGoogle Scholar
  47. Marillonnet S, Thoeringer C, Kandzia R, Klimyuk V, Gleba Y (2005) Systemic Agrobacterium tumefaciens-mediated transfection of viral replicons for efficient transient expression in plants. Nat Biotechnol 23:718–723CrossRefPubMedGoogle Scholar
  48. Martínez-González L, Rosales-Mendoza S, Soria-Guerra RE, Moreno-Fierros L, López-Revilla R, Korban S (2011) Oral immunization with a lettuce-derived Escherichia coli heat-labile toxin B subunit induces neutralizing antibodies in mice. Plant Cell Tissue Organ Cult 107:441–449CrossRefGoogle Scholar
  49. Mason HS, Lam DM, Arntzen CJ (1992) Expression of hepatitis B surface antigen in transgenic plants. Proc Natl Acad Sci USA 89(24):11745–11749CrossRefPubMedPubMedCentralGoogle Scholar
  50. Moravec T, Schmidt MA, Herman EM, Woodford-Thomas T (2007) Production of Escherichia coli heat labile toxin (LT) B subunit in soybean seed and analysis of its immunogenicity as an oral vaccine. Vaccine 25:1647–1657CrossRefPubMedGoogle Scholar
  51. Muthuselvi L, Dhathathreyan A (2006) Simple coacervates of zein to encapsulate Gitoxin. Colloids Surf B Biointerfaces 51:39–43CrossRefPubMedGoogle Scholar
  52. Nahampun HN, Bosworth B, Cunnick J, Mogler M, Wang K (2015) Expression of H3N2 nucleoprotein in maize seeds and immunogenicity in mice. Plant Cell Rep 34(6):969–980CrossRefPubMedGoogle Scholar
  53. Nochi T, Takagi H, Yuki Y, Yang L, Masumura T, Mejima M, Nakanishi U, Matsumura A, Uozumi A, Hiroi T, Morita S, Tanaka K, Takaiwa F, Kiyono H (2007) Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination. Proc Natl Acad Sci USA 104(26):10986–10991CrossRefPubMedPubMedCentralGoogle Scholar
  54. Nonthanum P, Lee Y, Padua GW (2012) Effect of gamma-zein on the rheological behavior of concentrated zein solutions. J Agric Food Chem 60:1742–1747CrossRefPubMedGoogle Scholar
  55. Orellana-Escobedo L, Korban SS, Rosales-Mendoza S (2014) Seed-based expression strategies. In: Rosales Mendoza (ed) Genetically engineered plants as a source of vaccines against wide spread diseases—an integrated view. Springer Science + Business Media, New York (ISBN 978-1-4939-0850-9)Google Scholar
  56. O’Ryan M, Vidal R, del Canto F, Carlos Salazar J, Montero D (2015) Vaccines for viral and bacterial pathogens causing acute gastroenteritis: part II: vaccines for Shigella, Salmonella, enterotoxigenic E. coli (ETEC) enterohemorrhagic E. coli (EHEC) and Campylobacter jejuni. Hum Vaccine Immunother 11(3):601–619CrossRefGoogle Scholar
  57. Patel A, Hu Y, Tiwari JK, Velikov KP (2010) Synthesis and characterization of zein-curcumin colloidal particles. Soft Matter 6:6192–6199CrossRefGoogle Scholar
  58. Pileri E, Mateu E (2016) Review on the transmission porcine reproductive and respiratory syndrome virus between pigs and farms and impact on vaccination. Vet Res 47(1):108CrossRefPubMedPubMedCentralGoogle Scholar
  59. Pniewski T, Kapusta J, Bociąg P, Wojciechowicz J, Kostrzak A, Gdula M, Fedorowicz-Strońska O, Wójcik P, Otta H, Samardakiewicz S, Wolko B, Płucienniczak A (2011) Low-dose oral immunization with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation. J Appl Genet 52(2):125–136CrossRefPubMedGoogle Scholar
  60. Regier MC, Taylor JD, Borcyk T, Yang Y, Pannier AK (2012) Fabrication and characterization of DNA-loaded zein nanospheres. J Nanobiotechnol 10:44CrossRefGoogle Scholar
  61. Rosales-Mendoza S, Salazar-González JA (2014) Immunological aspects of using plant cells as delivery vehicles for oral vaccines. Expert Rev Vaccines 13(6):737–749CrossRefPubMedGoogle Scholar
  62. Rosales-Mendoza S, Tello-Olea MA (2015) Carrot cells: a pioneering platform for biopharmaceuticals production. Mol Biotechnol 57(3):219–232CrossRefPubMedGoogle Scholar
  63. Rosales-Mendoza S, Rubio-Infante N, Zarazúa S, Govea-Alonso DO, Martel-Gallegos G, Moreno-Fierros L (2014) Plant-based vaccines for Alzheimer’s disease: an overview. Expert Rev Vaccines 13(3):429–441CrossRefPubMedGoogle Scholar
  64. Salazar-González JA, Bañuelos-Hernández B, Rosales-Mendoza S (2015) Current status of viral expression systems in plants and perspectives for oral vaccines development. Plant Mol Biol 87(3):203–217CrossRefPubMedGoogle Scholar
  65. Shah S, Hayden CA, Fischer ME, Rao AG, Howard JA (2015) Biochemical and biophysical characterization of maize-derived HBsAg for the development of an oral vaccine. Arch Biochem Biophys 588:41–49CrossRefPubMedPubMedCentralGoogle Scholar
  66. Shin MK, Jung MH, Lee WJ, Choi PS, Jang YS, Yoo HS (2011) Generation of transgenic corn-derived Actinobacillus pleuropneumoniae ApxIIA fused with cholera toxin B subunit as a vaccine candidate. J Vet Sci 12(4):401–403CrossRefPubMedPubMedCentralGoogle Scholar
  67. Shukla R, Cheryan M (2001) Zein: the industrial protein from corn. Ind Crop Prod 13:171–192CrossRefGoogle Scholar
  68. Sousa FF, Luzardo-Alvarez A, Blanco-Mendez J, Otero-Espinar FJ, Martin-Pastor M, Sandez-Macho I (2013) Use 1H NMR STD, waterLOGSY, and Langmuir monolayer techniques for characterization of drug-zein protein complexes. Eur J Pharm Biopharm 85:790–798CrossRefPubMedGoogle Scholar
  69. Stoger E, Vaquero C, Torres E, Sack M, Nicholson L, Drossard J, Williams S, Keen D, Perrin Y, Christou P, Fischer R (2000) Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies. Plant Mol Biol 42:583–590CrossRefPubMedGoogle Scholar
  70. Stoger E, Ma J, Fischer R, Christou P (2005) Sowing the seeds of success: pharmaceutical proteins from plants. Curr Opin Biotechnol 16:167–173CrossRefPubMedGoogle Scholar
  71. Streatfield SJ, Jilka JM, Hood EE, Turner DD, Bailey MR, Mayor JM, Woodard SL, Beifuss KK, Horn ME, Delaney DE, Tizard IR, Howard J (2001) Plant-based vaccines: unique advantages. Vaccine 19:2742–2748CrossRefPubMedGoogle Scholar
  72. Streatfield SJ, Mayor JM, Barker DK, Brooks C, Lamphear BJ, Woodard SL, Beifuss KK, Vicuna DV, Massey LA, Horn ME, Delaney DE, Nikolov ZL, Hood EE, Jilka JM, Howard JA (2002) Development of an edible subunit vaccine in corn against enterotoxigenic strains of Escherichia coli. In Vitro Cell Dev Biol Plant 38:11–17CrossRefGoogle Scholar
  73. Streatfield SJ, Lane JR, Brooks CA, Barker DK, Poage ML, Mayor JM, Lamphear BJ, Drees CF, Jilka JM, Hood EE, Howard JA (2003) Corn as a production system for human and animal vaccines. Vaccine 21:812–815CrossRefPubMedGoogle Scholar
  74. Su J, Zhu L, Sherman A, Wang X, Lin S, Kamesh A, Norikane JH, Streatfield SJ, Herzog RW, Daniell H (2015) Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B. Biomaterials 70:84–93CrossRefPubMedPubMedCentralGoogle Scholar
  75. Tacket CO, Pasetti MF, Edelman R, Howard JA, Streatfield S (2004) Immunogenicity of recombinant LT-B delivered orally to humans in transgenic corn. Vaccine 22:4385–4389CrossRefPubMedGoogle Scholar
  76. Tiwari S, Verma PC, Singh PK, Tuli R (2009) Plants as bioreactors for the production of vaccine antigens. Biotechnol Adv 27:449–467CrossRefPubMedGoogle Scholar
  77. Wongsasulak S, Puttipaiboon N, Yoovidhya T (2013) Fabrication, gastromucoadhesivity, swelling, and degradation of zein-chitosan composite ultrafine fibers. J Food Sci 78:N926–N935CrossRefPubMedGoogle Scholar
  78. World Health Organization (2014) http://www.who.int/medicines/areas/qualitysafety/qualityassurance/gmp/en/. Accessed Sept 2014
  79. Wu J, Yu L, Li L, Hu J, Zhou J, Zhou X (2007) Oral immunization with transgenic rice seeds expressing VP2 protein of infectious bursal disease virus induces protective immune responses in chickens. Plant Biotechnol J 5:570–578CrossRefPubMedGoogle Scholar
  80. Xiao D, Davidson PM, Zhong Q (2011) Spray-dried zein capsules with coencapsulated nisin and thymol as antimicrobial delivery system for enhanced antilisterial properties. J Agric Food Chem 59:7393–7404CrossRefPubMedGoogle Scholar
  81. Yang L, Hirose S, Suzuki K, Hiroi T, Takaiwa F (2012) Expression of hypoallergenic Der f 2 derivatives with altered intramolecular disulphide bonds induces the formation of novel ER-derived protein bodies in transgenic rice seeds. J Exp Bot 63:2947–2959CrossRefPubMedPubMedCentralGoogle Scholar
  82. Zhang SZ, Zhang GL, Rong TZ, Pan L, Zhou P, Zhang YG (2011) Transformation of two VP1 genes of O- and Asia 1-type foot-and-mouth disease virus into maize. Agric Sci China 10(5):661–667CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Sergio Rosales-Mendoza
    • 1
    Email author
  • Cristhian Sández-Robledo
    • 2
  • Bernardo Bañuelos-Hernández
    • 1
  • Carlos Angulo
    • 2
  1. 1.Laboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias QuímicasUniversidad Autónoma de San Luis PotosíSan Luis PotosíMexico
  2. 2.Centro de Investigaciones Biológicas del Noroeste, SC, Instituto Politécnico Nacional 195La PazMexico

Personalised recommendations