Skip to main content
SpringerLink
Log in

The Use of Probiotics as Vaccine Vectors to Prevent Viral Infections

  • Chapter
  • First Online:
New Insights on Antiviral Probiotics

Abstract

Vaccine is one of the most important strategies to struggle infectious diseases. In last decades, several types of vaccine have been used in clinical pathology to prevent complicated infections especially viral infections which cannot be treated with specific molecules such as human papillomavirus, rotavirus, and human immunodeficiency virus. The initial vaccination approaches used attenuated or inactivated pathogens. While inactivated vaccines are killed pathogens, attenuated vaccines consist of live microbes that lose their pathogenicity but preserve their antigenicity. Several factors hinder the development of efficient mucosal vaccines. Therefore, scientists try to overcome this problem by using probiotic bacteria as delivery systems of heterologous antigens which may help in designing such vaccines. In this chapter, we review the use of live probiotic strains as mucosal vaccine vectors to prevent viral infections.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CV-N:

Cyanovirin-N

DCpep:

DC-targeting peptide

DCs:

Dendritic cells

GRAS:

Generally regarded as safe

HA:

Hemagglutinin

HIV:

Human immunodeficiency virus

HPV:

Human papillomavirus

IL-12:

Interleukin 2

IL-1β:

Interleukin 1 beta

IL-2:

Interleukin 2

IL-6:

Interleukin 2

LAB:

Lactic acid bacteria

LTB:

Heat-labile toxin B

MPER:

Membrane proximal external region

sIgA:

Secretory IgA

SlpA:

Surface layer protein

TLR:

Toll-like receptors

References

  1. Nabel GJ. Designing tomorrow's vaccines. N Engl J Med. 2013;368:551–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gerdts V, Mutwiri GK, Tikoo SK, Babiuk LA. Mucosal delivery of vaccines in domestic animals. Vet Res. 2006;37:487–510.

    Article  CAS  PubMed  Google Scholar 

  3. Plotkin SA. Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010;17:1055–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nascimento IP, Leite LC. Recombinant vaccines and the development of new vaccine strategies. Braz J Med Biol Res. 2012;45:1102–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Neutra MR, Kozlowski PA. Mucosal vaccines: the promise and the challenge. Nat Rev Immunol. 2006;6:148–58.

    Article  CAS  PubMed  Google Scholar 

  6. Srivastava A, Gowda DV, Madhunapantula SV, Shinde CG, Iyer M. Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles. APMIS. 2015;123:275–88.

    Article  CAS  PubMed  Google Scholar 

  7. Lycke N. Recent progress in mucosal vaccine development: potential and limitations. Nat Rev Immunol. 2012;12:592–605.

    Article  CAS  PubMed  Google Scholar 

  8. Pavot V, Rochereau N, Genin C, Verrier B, Paul S. New insights in mucosal vaccine development. Vaccine. 2012;30:142–54.

    Article  CAS  PubMed  Google Scholar 

  9. Nizard M, Diniz MO, Roussel H, Tran T, Ferreira LC, et al. Mucosal vaccines: novel strategies and applications for the control of pathogens and tumors at mucosal sites. Hum Vaccin Immunother. 2014;10:2175–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gebril A, Alsaadi M, Acevedo R, Mullen AB, Ferro VA. Optimizing efficacy of mucosal vaccines. Expert Rev Vaccines. 2012;11:1139–55.

    Article  CAS  PubMed  Google Scholar 

  11. Czerkinsky C, Anjuere F, McGhee JR, George-Chandy A, Holmgren J, et al. Mucosal immunity and tolerance: relevance to vaccine development. Immunol Rev. 1999;170:197–222.

    Article  CAS  PubMed  Google Scholar 

  12. Lin IY, Van TT, Smooker PM. Live-attenuated bacterial vectors: tools for vaccine and therapeutic agent delivery. Vaccines (Basel). 2015;3:940–72.

    Article  Google Scholar 

  13. Luca S, Mihaescu T. History of BCG vaccine. Maedica (Buchar). 2013;8:53–8.

    Google Scholar 

  14. Germanier R, Fuer E. Isolation and characterization of Gal E mutant Ty 21a of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine. J Infect Dis. 1975;131:553–8.

    Article  CAS  PubMed  Google Scholar 

  15. Galan JE, Curtiss 3rd R. Virulence and vaccine potential of phoP mutants of Salmonella typhimurium. Microb Pathog. 1989;6:433–43.

    Article  CAS  PubMed  Google Scholar 

  16. Medina E, Paglia P, Nikolaus T, Muller A, Hensel M, et al. Pathogenicity island 2 mutants of Salmonella typhimurium are efficient carriers for heterologous antigens and enable modulation of immune responses. Infect Immun. 1999;67:1093–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Shata MT, Stevceva L, Agwale S, Lewis GK, Hone DM. Recent advances with recombinant bacterial vaccine vectors. Mol Med Today. 2000;6:66–71.

    Article  CAS  PubMed  Google Scholar 

  18. Mercenier A, Muller-Alouf H, Grangette C. Lactic acid bacteria as live vaccines. Curr Issues Mol Biol. 2000;2:17–25.

    CAS  PubMed  Google Scholar 

  19. Curtiss 3rd R. Bacterial infectious disease control by vaccine development. J Clin Invest. 2002;110:1061–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tarahomjoo S. Development of vaccine delivery vehicles based on lactic acid bacteria. Mol Biotechnol. 2012;51:183–99.

    Article  CAS  PubMed  Google Scholar 

  21. Wyszynska A, Kobierecka P, Bardowski J, Jagusztyn-Krynicka EK. Lactic acid bacteria--20 years exploring their potential as live vectors for mucosal vaccination. Appl Microbiol Biotechnol. 2015;99:2967–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sleator RD. Probiotics -- a viable therapeutic alternative for enteric infections especially in the developing world. Discov Med. 2010;10:119–24.

    PubMed  Google Scholar 

  23. Yu Q, Zhu L, Kang H, Yang Q. Mucosal Lactobacillus vectored vaccines. Hum Vaccin Immunother. 2013;9:805–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cortes-Perez NG, Lefevre F, Corthier G, Adel-Patient K, Langella P, et al. Influence of the route of immunization and the nature of the bacterial vector on immunogenicity of mucosal vaccines based on lactic acid bacteria. Vaccine. 2007;25:6581–8.

    Article  CAS  PubMed  Google Scholar 

  25. Wells JM, Mercenier A. Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria. Nat Rev Microbiol. 2008;6:349–62.

    Article  CAS  PubMed  Google Scholar 

  26. Bahey-El-Din M. Lactococcus lactis-based vaccines from laboratory bench to human use: an overview. Vaccine. 2012;30:685–90.

    Article  CAS  PubMed  Google Scholar 

  27. Bermudez-Humaran LG, Kharrat P, Chatel JM, Langella P. Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Microb Cell Fact. 2011;10 Suppl 1:S4.

    Article  PubMed  Google Scholar 

  28. Wells J. Mucosal vaccination and therapy with genetically modified lactic acid bacteria. Annu Rev Food Sci Technol. 2011;2:423–45.

    Article  CAS  PubMed  Google Scholar 

  29. Steidler L, Robinson K, Chamberlain L, Schofield KM, Remaut E, et al. Mucosal delivery of murine interleukin-2 (IL-2) and IL-6 by recombinant strains of Lactococcus lactis coexpressing antigen and cytokine. Infect Immun. 1998;66:3183–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Bermudez-Humaran LG, Cortes-Perez NG, Lefevre F, Guimaraes V, Rabot S, et al. A novel mucosal vaccine based on live Lactococci expressing E7 antigen and IL-12 induces systemic and mucosal immune responses and protects mice against human papillomavirus type 16-induced tumors. J Immunol. 2005;175:7297–302.

    Article  CAS  PubMed  Google Scholar 

  31. Li Y, Li X, Liu H, Zhuang S, Yang J, et al. Intranasal immunization with recombinant Lactococci carrying human papillomavirus E7 protein and mouse interleukin-12 DNA induces E7-specific antitumor effects in C57BL/6 mice. Oncol Lett. 2014;7:576–82.

    PubMed  Google Scholar 

  32. Kajikawa A, Masuda K, Katoh M, Igimi S. Adjuvant effects for oral immunization provided by recombinant Lactobacillus casei secreting biologically active murine interleukin-1{beta}. Clin Vaccine Immunol. 2010;17:43–8.

    Article  CAS  PubMed  Google Scholar 

  33. Cortes-Perez NG, da Costa Medina LF, Lefevre F, Langella P, Bermudez-Humaran LG. Production of biologically active CXC chemokines by Lactococcus lactis: evaluation of its potential as a novel mucosal vaccine adjuvant. Vaccine. 2008;26:5778–83.

    Article  CAS  PubMed  Google Scholar 

  34. Kuczkowska K, Mathiesen G, Eijsink VG, Oynebraten I. Lactobacillus plantarum displaying CCL3 chemokine in fusion with HIV-1 Gag derived antigen causes increased recruitment of T cells. Microb Cell Fact. 2015;14:169.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Qiao X, Li G, Wang X, Li X, Liu M, et al. Recombinant porcine rotavirus VP4 and VP4-LTB expressed in Lactobacillus casei induced mucosal and systemic antibody responses in mice. BMC Microbiol. 2009;9:249.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kajikawa A, Satoh E, Leer RJ, Yamamoto S, Igimi S. Intragastric immunization with recombinant Lactobacillus casei expressing flagellar antigen confers antibody-independent protective immunity against Salmonella enterica serovar Enteritidis. Vaccine. 2007;25:3599–605.

    Article  CAS  PubMed  Google Scholar 

  37. Lee S, Belitsky BR, Brinker JP, Kerstein KO, Brown DW, et al. Development of a Bacillus subtilis-based rotavirus vaccine. Clin Vaccine Immunol. 2010;17:1647–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mohamadzadeh M, Duong T, Sandwick SJ, Hoover T, Klaenhammer TR. Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge. Proc Natl Acad Sci U S A. 2009;106:4331–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sorokulova I. Recombinant probiotics: future perspectives in disease treatment. J Prob Health. 2014;2:e109.

    Article  Google Scholar 

  40. Lehner T, Bergmeier L, Wang Y, Tao L, Mitchell E. A rational basis for mucosal vaccination against HIV infection. Immunol Rev. 1999;170:183–96.

    Article  CAS  PubMed  Google Scholar 

  41. Xin KQ, Hoshino Y, Toda Y, Igimi S, Kojima Y, et al. Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env. Blood. 2003;102:223–8.

    Article  CAS  PubMed  Google Scholar 

  42. Gram GJ, Fomsgaard A, Thorn M, Madsen SM, Glenting J. Immunological analysis of a Lactococcus lactis-based DNA vaccine expressing HIV gp120. Genet Vaccines Ther. 2007;5:3.

    PubMed  PubMed Central  Google Scholar 

  43. Kajikawa A, Zhang L, Long J, Nordone S, Stoeker L, et al. Construction and immunological evaluation of dual cell surface display of HIV-1 gag and Salmonella enterica serovar Typhimurium FliC in Lactobacillus acidophilus for vaccine delivery. Clin Vaccine Immunol. 2012;19:1374–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kajikawa A, Zhang L, LaVoy A, Bumgardner S, Klaenhammer TR, et al. Mucosal Immunogenicity of Genetically Modified Lactobacillus acidophilus Expressing an HIV-1 Epitope within the Surface Layer Protein. PLoS One. 2015;10:e0141713.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Fauci AS, Marovich MA, Dieffenbach CW, Hunter E, Buchbinder SP. Immunology immune activation with HIV vaccines. Science. 2014;344:49–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chang TL, Chang CH, Simpson DA, Xu Q, Martin PK, et al. Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. Proc Natl Acad Sci U S A. 2003;100:11672–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu X, Lagenaur LA, Simpson DA, Essenmacher KP, Frazier-Parker CL, et al. Engineered vaginal lactobacillus strain for mucosal delivery of the human immunodeficiency virus inhibitor cyanovirin-N. Antimicrob Agents Chemother. 2006;50:3250–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lei H, Xu Y, Chen J, Wei X, Lam DM. Immunoprotection against influenza H5N1 virus by oral administration of enteric-coated recombinant Lactococcus lactis mini-capsules. Virology. 2010;407:319–24.

    Article  CAS  PubMed  Google Scholar 

  49. Wang Z, Yu Q, Gao J, Yang Q. Mucosal and systemic immune responses induced by recombinant Lactobacillus spp. expressing the hemagglutinin of the avian influenza virus H5N1. Clin Vaccine Immunol. 2012;19:174–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Szatraj K, Szczepankowska AK, Saczynska V, Florys K, Gromadzka B, et al. Expression of avian influenza haemagglutinin (H5) and chicken interleukin 2 (chIL-2) under control of the ptcB promoter in Lactococcus lactis. Acta Biochim Pol. 2014;61:609–14.

    PubMed  Google Scholar 

  51. Shi SH, Yang WT, Yang GL, Cong YL, Huang HB, et al. Immunoprotection against influenza virus H9N2 by the oral administration of recombinant Lactobacillus plantarumNC8 expressing hemagglutinin in BALB/c mice. Virology. 2014;464-465:166–76.

    Article  CAS  PubMed  Google Scholar 

  52. Shi SH, Yang WT, Yang GL, Zhang XK, Liu YY, et al. Lactobacillus plantarum vaccine vector expressing hemagglutinin provides protection against H9N2 challenge infection. Virus Res. 2016;211:46–57.

    Article  CAS  PubMed  Google Scholar 

  53. Chowdhury MY, Li R, Kim JH, Park ME, Kim TH, et al. Mucosal vaccination with recombinant Lactobacillus casei-displayed CTA1-conjugated consensus matrix protein-2 (sM2) induces broad protection against divergent influenza subtypes in BALB/c mice. PLoS One. 2014;9:e94051.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Angel J, Franco MA, Greenberg HB. Rotavirus vaccines: recent developments and future considerations. Nat Rev Microbiol. 2007;5:529–39.

    Article  CAS  PubMed  Google Scholar 

  55. Ward RL. Rotavirus vaccines: how they work or don't work. Expert Rev Mol Med. 2008;10:e5.

    Article  PubMed  Google Scholar 

  56. Perez CA, Eichwald C, Burrone O, Mendoza D. Rotavirus vp7 antigen produced by Lactococcus lactis induces neutralizing antibodies in mice. J Appl Microbiol. 2005;99:1158–64.

    Article  CAS  PubMed  Google Scholar 

  57. Li YJ, Ma GP, Li GW, Qiao XY, Ge JW, et al. Oral vaccination with the porcine rotavirus VP4 outer capsid protein expressed by Lactococcus lactis induces specific antibody production. J Biomed Biotechnol. 2010;2010:708460.

    PubMed  PubMed Central  Google Scholar 

  58. Marelli B, Perez AR, Banchio C, de Mendoza D, Magni C. Oral immunization with live Lactococcus lactis expressing rotavirus VP8 subunit induces specific immune response in mice. J Virol Methods. 2011;175:28–37.

    Article  CAS  PubMed  Google Scholar 

  59. zur Hausen H. Human papillomaviruses in the pathogenesis of anogenital cancer. Virology. 1991;184:9–13.

    Article  CAS  PubMed  Google Scholar 

  60. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2:342–50.

    Article  CAS  PubMed  Google Scholar 

  61. Angioli R, Lopez S, Aloisi A, Terranova C, De Cicco C, et al. Ten years of HPV vaccines: state of art and controversies. Crit Rev Oncol Hematol. 2016;102:65–72.

    Article  PubMed  Google Scholar 

  62. Kumar S, Biswas M, Jose T. HPV vaccine: current status and future directions. Med J Armed Forces India. 2015;71:171–7.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Pozzi G, Contorni M, Oggioni MR, Manganelli R, Tommasino M, et al. Delivery and expression of a heterologous antigen on the surface of streptococci. Infect Immun. 1992;60:1902–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Bermudez-Humaran LG, Langella P, Miyoshi A, Gruss A, Guerra RT, et al. Production of human papillomavirus type 16 E7 protein in Lactococcus lactis. Appl Environ Microbiol. 2002;68:917–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Medaglini D, Rush CM, Sestini P, Pozzi G. Commensal bacteria as vectors for mucosal vaccines against sexually transmitted diseases: vaginal colonization with recombinant streptococci induces local and systemic antibodies in mice. Vaccine. 1997;15:1330–7.

    Article  CAS  PubMed  Google Scholar 

  66. Oggioni MR, Manganelli R, Contorni M, Tommasino M, Pozzi G. Immunization of mice by oral colonization with live recombinant commensal streptococci. Vaccine. 1995;13:775–9.

    Article  CAS  PubMed  Google Scholar 

  67. Cortes-Perez NG, Bermudez-Humaran LG, Le Loir Y, Rodriguez-Padilla C, Gruss A, et al. Mice immunization with live lactococci displaying a surface anchored HPV-16 E7 oncoprotein. FEMS Microbiol Lett. 2003;229:37–42.

    Article  CAS  PubMed  Google Scholar 

  68. Bermudez-Humaran LG, Cortes-Perez NG, Le Loir Y, Alcocer-Gonzalez JM, Tamez-Guerra RS, et al. An inducible surface presentation system improves cellular immunity against human papillomavirus type 16 E7 antigen in mice after nasal administration with recombinant lactococci. J Med Microbiol. 2004;53:427–33.

    Article  CAS  PubMed  Google Scholar 

  69. Adachi K, Kawana K, Yokoyama T, Fujii T, Tomio A, et al. Oral immunization with a Lactobacillus casei vaccine expressing human papillomavirus (HPV) type 16 E7 is an effective strategy to induce mucosal cytotoxic lymphocytes against HPV16 E7. Vaccine. 2010;28:2810–7.

    Article  CAS  PubMed  Google Scholar 

  70. Kawana K, Adachi K, Kojima S, Taguchi A, Tomio K, et al. Oral vaccination against HPV E7 for treatment of cervical intraepithelial neoplasia grade 3 (CIN3) elicits E7-specific mucosal immunity in the cervix of CIN3 patients. Vaccine. 2014;32:6233–9.

    Article  CAS  PubMed  Google Scholar 

  71. Poo H, Pyo HM, Lee TY, Yoon SW, Lee JS, et al. Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice. Int J Cancer. 2006;119:1702–9.

    Article  CAS  PubMed  Google Scholar 

  72. Ribelles P, Benbouziane B, Langella P, Suarez JE, Bermudez-Humaran LG. Protection against human papillomavirus type 16-induced tumors in mice using non-genetically modified lactic acid bacteria displaying E7 antigen at its surface. Appl Microbiol Biotechnol. 2013;97:1231–9.

    Article  CAS  PubMed  Google Scholar 

  73. Aires KA, Cianciarullo AM, Carneiro SM, Villa LL, Boccardo E, et al. Production of human papillomavirus type 16 L1 virus-like particles by recombinant Lactobacillus casei cells. Appl Environ Microbiol. 2006;72:745–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Yoon SW, Lee TY, Kim SJ, Lee IH, Sung MH, et al. Oral administration of HPV-16 L2 displayed on Lactobacillus casei induces systematic and mucosal cross-neutralizing effects in Balb/c mice. Vaccine. 2012;30:3286–94.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Microbiologie Environnement et Santé (LMSE), Doctoral School of Sciences and Technology/Faculty of Public Health Lebanese University, Tripoli, Lebanon

    Bachar ISMAIL

Authors
  1. Bachar ISMAIL
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

ISMAIL, B. (2017). The Use of Probiotics as Vaccine Vectors to Prevent Viral Infections. In: New Insights on Antiviral Probiotics. Springer, Cham. https://doi.org/10.1007/978-3-319-49688-7_2

Download citation

Publish with us

Policies and ethics

Search

Navigation