Vector development timeline for mucosal vaccination and treatment of disease using Lactococcus lactis and design approaches of next generation food grade plasmids

Frontiers in Microbiology

Volumn 9, Issue AUG, 2018, Pages

  de Castro, Camila Prosperi ^a,b   Drumond, Mariana M ^a,c   Batista, Viviane L ^a   Nunes, Amanda ^a   Mancha Agresti, Pamela ^a   Azevedo, Vasco ^a  

^a FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

^b University of Kroton   (Brazil)

^c CENTRO FEDERAL DE EDUCAÇÃO TECNOLÓGICA DE MINAS GERAIS   (Brazil)

Author keywords

DNA vaccine; Expression systems; Food grade vectors; Lactic acid bacteria; Recombinant L. lactis

Indexed keywords

DNA VACCINE;

BIOTECHNOLOGY; FERMENTATION TECHNIQUE; FLOW CYTOMETRY; FLUORESCENCE MICROSCOPY; FOOD INDUSTRY; FOOD PRESERVATION; GENE EXPRESSION; GENE SEQUENCE; INFLAMMATORY BOWEL DISEASE; LACTIC ACID BACTERIUM; LACTOCOCCUS LACTIS; NEXT GENERATION SEQUENCING; NONHUMAN; PLASMID; PROTEIN TARGETING; REVIEW; VACCINATION;

EID: 85051534309     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2018.01805     Document Type: Review

References (81)

1. Benbouziane, B., Ribelles, P., Aubry, C., Martin, R., Kharrat, P., Riazi, A., et al. (2013). Development of a Stress-Inducible Controlled Expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces. J. Biotechnol. 168, 120-129. doi: 10.1016/j.jbiotec.2013.04.019
2. Berlec, A., Škrlec, K., Kocjan, J., Olenic, M., and Štrukelj, B. (2018). Single plasmid systems for inducible dual protein expression and for CRISPR-Cas9/CRISPRi gene regulation in lactic acid bacterium Lactococcus lactis. Sci. Rep. 8:1009. doi: 10.1038/s41598-018-19402-1
3. Berlec, A., and Strukelj, B. (2009). Novel applications of recombinant lactic acid bacteria in therapy and in metabolic engineering. Recent Pat. Biotechnol. 3, 77-87. doi: 10.2174/187220809788700175
4. Berlec, A., Završnik, J., Butinar, M., Turk, B., and Štrukelj, B. (2015). In vivo imaging of Lactococcus lactis, Lactobacillus plantarum and Escherichia coli expressing infrared fluorescent protein in mice. Microb. Cell Fact. 14:181. doi: 10.1186/s12934-015-0376-4
5. Bermudez-Humaran, L. G., Cortes-Perez, N. G., Lefevre, F., Guimaraes, V., Rabot, S., Alcocer-Gonzalez, J. M., et al. (2005). 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. 175, 7297-7302. doi: 10.4049/jimmunol.175.11.7297
6. Bermúdez-Humarán, L. G., Nouaille, S., Zilberfarb, V., Corthier, G., Gruss, A., Langella, P., et al. (2007). Effects of intranasal administration of a leptin-secreting Lactococcus lactis recombinant on food intake, body weight, and immune response of mice. Appl. Environ. Microbiol. 73, 5300-5307. doi: 10.1128/AEM.00295-07
7. Bolotin, A., Quinquis, B., Sorokin, A., and Ehrlich, S. D. (2005). Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151, 2551-2561. doi: 10.1099/mic.0.28048-0
8. Braat, H., Rottiers, P., Hommes, D. W., Huyghebaert, N., Remaut, E., Remon, J.-P., et al. (2006). A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin. Gastroenterol. Hepatol. 4, 754-759. doi: 10.1016/j.cgh.2006.03.028
9. Carvalho, R. D. O., Morais, K., Pereira, V. B., Gomes-Santos, A. C., Luerce, T. D., de Azevedo, M. S., et al. (2016). Oral administration of Lactococcus lactis expressing recombinant 15-lipoxygenase-1 (15 LOX-1) modulates chemically induced colitis in mice. Med. Res. Arch. 4:1. doi: 10.18103/mra.v4i7.612
10. Cho, S., Shin, J., and Cho, B.-K. (2018). Applications of CRISPR/cas system to bacterial metabolic engineering. Int. J. Mol. Sci. 19:E1089. doi: 10.3390/ijms19041089
11. Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819-823. doi: 10.1126/science.1231143
12. Cotter, P. D., Hill, C., and Ross, R. P. (2003). A food-grade approach for functional analysis and modification of native plasmids in Lactococcus lactis. Appl. Environ. Microbiol. 69, 702-706. doi: 10.1128/AEM.69.1.702-706.2003
13. de Azevedo, M. S. P., Rocha, C. S., Electo, N., Pontes, D. S., Molfetta, J. B., Gonçalves, E. D. C., et al. (2012). Cytoplasmic and extracellular expression of pharmaceutical-grade mycobacterial 65-kDa heat shock protein in Lactococcus lactis. Genet. Mol. Res. 11, 1146-1157. doi: 10.4238/2012.April.27.14
14. de Moreno de LeBlanc, A., LeBlanc, J. G., Perdigón, G., Miyoshi, A., Langella, P., Azevedo, V., et al. (2008). Oral administration of a catalase-producing Lactococcus lactis can prevent a chemically induced colon cancer in mice. J. Med. Microbiol. 57, 100-105. doi: 10.1099/jmm.0.47403-0
15. De Vos, W. M. (1999). Gene expression systems for lactic acid bacteria. Curr. Opin. Microbiol. 2, 289-295. doi: 10.1016/S1369-5274(99)80050-2
16. de Vos, W. M., Kleerebezem, M., and Kuipers, O. P. (1997). Expression systems for industrial gram-positive bacteria with low guanine and cytosine content. Curr. Opin. Biotechnol. 8, 547-553. doi: 10.1016/S0958-1669(97)80027-4
17. De Vos, W. M., and Simons, G. F. M. (1994). 'Gene cloning and expression systems in Lactococci,' in Genetics and Biotechnology of Lactic Acid Bacteria, eds M. J. Gasson and W. de Vos (Dordrecht: Springer), 52-105. doi: 10.1007/978-94-011-1340-3_2
18. Deveau, H., Barrangou, R., Garneau, J. E., Labonté, J., Fremaux, C., Boyaval, P., et al. (2008). Phage response to CRISPR-encoded resistance in Streptococcus thermophilus. J. Bacteriol. 190, 1390-1400. doi: 10.1128/JB.01412-07
19. Di Bella, S., Ascenzi, P., Siarakas, S., Petrosillo, N., and di Masi, A. (2016). Clostridium difficile toxins A and B: insights into pathogenic properties and extraintestinal effects. Toxins 8:E134. doi: 10.3390/toxins8050134
20. Dickely, F., Nilsson, D., Hansen, E. B., and Johansen, E. (1995). Isolation of Lactococcus lactis nonsense suppressors and construction of a food-grade cloning vector. Mol. Microbiol. 15, 839-847. doi: 10.1111/j.1365-2958.1995.tb02354.x
21. Emond, E., Lavallée, R., Drolet, G., Moineau, S., and LaPointe, G. (2001). Molecular characterization of a theta replication plasmid and its use for development of a two-component food-grade cloning system for Lactococcus lactis. Appl. Environ. Microbiol. 67, 1700-1709. doi: 10.1128/AEM.67.4.1700-1709.2001
22. Galvin, T. A., Muller, J., and Khan, A. S. (2000). Effect of different promoters on immune responses elicited by HIV-1 gag/env multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina. Vaccine 18, 2566-2583. doi: 10.1016/S0264-410X(99)00569-1
23. Glenting, J., Madsen, S. M., Vrang, A., Fomsgaard, A., and Israelsen, H. (2002).). A plasmid selection system in Lactococcus lactis and its use for gene expression in L. lactis and human kidney fibroblasts. Appl. Environ. Microbiol. 68, 5051-5056. doi: 10.1128/AEM.68.10.5051-5056.2002
24. Gomes-Santos, A. C., de Oliveira, R. P., Moreira, T. G., Castro-Junior, A. B., Horta, B. C., Lemos, L., et al. (2017). Hsp65-producing Lactococcus lactis prevents inflammatory intestinal disease in mice by IL-10-and TLR2-dependent pathways. Front. Immunol. 8:30. doi: 10.3389/fimmu.2017.00030
25. Gosalbes, M. J., Esteban, C. D., Galán, J. L., and Pérez-Martínez, G. (2000). Integrative food-grade expression system based on the lactose regulon of Lactobacillus casei. Appl. Environ. Microbiol. 66, 4822-4828. doi: 10.1128/AEM.66.11.4822-4828.2000
26. Guimarães, V., Innocentin, S., Chatel, J.-M., Lefèvre, F., Langella, P., Azevedo, V., et al. (2009). A new plasmid vector for DNA delivery using Lactococci. Genet. Vaccines Ther. 7:4. doi: 10.1186/1479-0556-7-4
27. Huang, M. T., and Gorman, C. M. (1990). Intervening sequences increase efficiency of RNA 3' processing and accumulation of cytoplasmic RNA. Nucleic Acids Res. 18, 937-947. doi: 10.1093/nar/18.4.937
28. Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., and Nakata, A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J. Bacteriol. 169, 5429-5433. doi: 10.1128/jb.169.12.5429-5433.1987
29. Jiang, W., Bikard, D., Cox, D., Zhang, F., and Marraffini, L. A. (2013). RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat. Biotechnol. 31, 233-239. doi: 10.1038/nbt.2508
30. Joutsjoki, V., Luoma, S., Tamminen, M., Kilpi, M., Johansen, E., and Palva, A. (2002). Recombinant Lactococcus starters as a potential source of additional peptidolytic activity in cheese ripening. J. Appl. Microbiol. 92, 1159-1166. doi: 10.1046/j.1365-2672.2002.01652.x
31. Kleerebezem, M., Beerthuyzen, M. M., Vaughan, E. E., De Vos, W. M., and Kuipers, O. P. (1997a). Controlled gene expression systems for lactic acid bacteria: transferable nisin-inducible expression cassettes for Lactococcus, Leuconostoc, and Lactobacillus spp. Appl. Environ. Microbiol. 63, 4581-4584
32. Kleerebezem, M., Quadri, L. E. N., Kuipers, O. P., and de Vos, W. M. (1997b). Quorum sensing by peptide pheromones and two-component signal-transduction systems in gram-positive bacteria. Mol. Microbiol. 24, 895-904. doi: 10.1046/j.1365-2958.1997.4251782.x
33. Kok, J., Van Der Vossen, J. M., and Venema, G. (1984). Construction of plasmid cloning vectors for lactic streptococci which also replicate in Bacillus subtilis and Escherichia coli. Appl. Environ. Microbiol. 48, 726-731
34. Kuipers, O. P., Beerthuyzen, M. M., de Ruyter, P. G., Luesink, E. J., and de Vos, W. M. (1995). Autoregulation of nisin biosynthesis in Lactococcus lactis by signal transduction. J. Biol. Chem. 270, 27299-27304. doi: 10.1074/jbc.270.45.27299
35. Kutzler, M. A., and Weiner, D. B. (2008). DNA vaccines: ready for prime time? Nat. Rev. Genet. 9, 776-788. doi: 10.1038/nrg2432
36. Landete, J. M. (2017). A review of food-grade vectors in lactic acid bacteria: from the laboratory to their application. Crit. Rev. Biotechnol. 37, 296-308. doi: 10.3109/07388551.2016.1144044
37. Le Loir, Y., Azevedo, V., Oliveira, S. C., Freitas, D. A., Miyoshi, A., Bermúdez-Humarán, L. G., et al. (2005). Protein secretion in Lactococcus lactis: an efficient way to increase the overall heterologous protein production. Microb. Cell Fact. 4:2. doi: 10.1186/1475-2859-4-2
38. Limaye, S. A., Haddad, R. I., Cilli, F., Sonis, S. T., Colevas, A. D., Brennan, M. T., et al. (2013). Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy. Cancer 119, 4268-4276. doi: 10.1002/cncr.28365
39. Liu, C. Q., Leelawatcharamas, V., Harvey, M. L., and Dunn, N. W. (1996). Cloning vectors for Lactococci based on a plasmid encoding resistance to cadmium. Curr. Microbiol. 33, 35-39. doi: 10.1007/s002849900070
40. Lokman, B. C., Leer, R. J., van Sorge, R., and Pouwels, P. H. (1994). Promoter analysis and transcriptional regulation of Lactobacillus pentosus genes involved in xylose catabolism. Mol. Gen. Genet. 245, 117-125. doi: 10.1007/BF00279757
41. MacCormick, C. A., Griffin, H. G., and Gasson, M. J. (1995). Construction of a food-grade host/vector system for Lactococcus lactis based on the lactose operon. FEMS Microbiol. Lett. 127, 105-109. doi: 10.1111/j.1574-6968.1995.tb07457.x
42. Madsen, S. M., Arnau, J., Vrang, A., Givskov, M., and Israelsen, H. (1999). Molecular characterization of the pH-inducible and growth phase-dependent promoter P170 of Lactococcus lactis. Mol. Microbiol. 32, 75-87. doi: 10.1046/j.1365-2958.1999.01326.x
43. Makarova, K. S., and Koonin, E. V. (2007). Evolutionary genomics of lactic acid bacteria. J. Bacteriol. 189, 1199-1208. doi: 10.1128/JB.01351-06
44. Makarova, K. S., Wolf, Y. I., Alkhnbashi, O. S., Costa, F., Shah, S. A., Saunders, S. J., et al. (2015). An updated evolutionary classification of CRISPR-cas systems. Nat. Rev. Microbiol. 13, 722-736. doi: 10.1038/nrmicro3569
45. Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., et al. (2013). RNA-guided human genome engineering via Cas9. Science 339, 823-826. doi: 10.1126/science.1232033
46. Mancha-Agresti, P., de Castro, C. P., dos Santos, J. S. C., Araujo, M. A., Pereira, V. B., LeBlanc, J. G., et al. (2017). Recombinant invasive Lactococcus lactis carrying a DNA vaccine coding the Ag85A antigen increases INF-γ, IL-6, and TNF-α cytokines after intranasal immunization. Front. Microbiol. 8:1263. doi: 10.3389/fmicb.2017.01263
47. Mancha-Agresti, P., Drumond, M. M., Rosa, do Carmo, F. L., Santos, M. M., Coelho, et al. (2016). A new broad range plasmid for DNA delivery in eukaryotic cells using lactic acid bacteria: in vitro and in vivo assays. Mol. Ther. Methods Clin. Dev. 4, 83-91. doi: 10.1016/j.omtm.2016.12.005
48. Marinho, F. A. V., Pacífico, L. G. G., Miyoshi, A., Azevedo, V., Le Loir, Y., Guimarães, V. D., et al. (2010). An intranasal administration of Lactococcus lactis strains expressing recombinant interleukin-10 modulates acute allergic airway inflammation in a murine model. Clin. Exp. Allergy 40, 1541-1551. doi: 10.1111/j.1365-2222.2010.03502.x
49. Mercenier, A., Müller-Alouf, H., and Grangette, C. (2000). Lactic acid bacteria as live vaccines. Curr. Issues Mol. Biol. 2, 17-25
50. Miyoshi, A., Bermúdez-Humarán, L. G., Ribeiro, L. A., Le Loir, Y., Oliveira, S. C., Langella, P., et al. (2006). Heterologous expression of Brucella abortus GroEL heat-shock protein in Lactococcus lactis. Microb. Cell Fact. 5:14. doi: 10.1186/1475-2859-5-14
51. Miyoshi, A., Jamet, E., Commissaire, J., Renault, P., Langella, P., and Azevedo, V. (2004). A xylose-inducible expression system for Lactococcus lactis. FEMS Microbiol. Lett. 239, 205-212. doi: 10.1016/j.femsle.2004.08.018
52. Mu, D., Montalbán-López, M., Masuda, Y., and Kuipers, O. P. (2013). Zirex: a novel zinc-regulated expression system for Lactococcus lactis. Appl. Environ. Microbiol. 79, 4503-4508. doi: 10.1128/AEM.00866-13
53. Oh, J.-H., and van Pijkeren, J.-P. (2014). CRISPR-Cas9-assisted recombineering in Lactobacillus reuteri. Nucleic Acids Res. 42:e131. doi: 10.1093/nar/gku623
54. Oliveira, P. H., and Mairhofer, J. (2013). Marker-free plasmids for biotechnological applications? implications and perspectives. Trends Biotechnol. 31, 539-547. doi: 10.1016/j.tibtech.2013.06.001
55. O'Sullivan, D. J., and Klaenhammer, T. R. (1993). High-and low-copy-number Lactococcus shuttle cloning vectors with features for clone screening. Gene 137, 227-231. doi: 10.1016/0378-1119(93)90011-Q
56. Payne, J., MacCormick, C. A., Griffin, H. G., and Gasson, M. J. (1996). Exploitation of a chromosomally integrated lactose operon for controlled gene expression in Lactococcus lactis. FEMS Microbiol. Lett. 136, 19-24. doi: 10.1111/j.1574-6968.1996.tb08019.x
57. Pereira, V. B., da Cunha, V. P., Preisser, T. M., Souza, B. M., Turk, M. Z., De Castro, C. P., et al. (2017). Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response. J. Appl. Microbiol. 122, 1657-1662. doi: 10.1111/jam.13449
58. Pereira, V. B., Saraiva, T. D. L., Souza, B. M., Zurita-Turk, M., Azevedo, M. S. P., De Castro, C. P., et al. (2014). Development of a new DNA vaccine based on mycobacterial ESAT-6 antigen delivered by recombinant invasive Lactococcus lactis FnBPA+. Appl. Microbiol. Biotechnol. 99, 1817-1826. doi: 10.1007/s00253-014-6285-3
59. Pontes, D., Azevedo, M., Innocentin, S., Blugeon, S., Lefévre, F., Azevedo, V., et al. (2014). Immune response elicited by DNA vaccination using Lactococcus lactis is modified by the production of surface exposed pathogenic protein. PLoS One 9:e84509. doi: 10.1371/journal.pone.0084509
60. Pontes, D. S., de Azevedo, M. S. P., Chatel, J.-M., Langella, P., Azevedo, V., and Miyoshi, A. (2011). Lactococcus lactis as a live vector: heterologous protein production and DNA delivery systems. Protein Expr. Purif. 79, 165-175. doi: 10.1016/j.pep.2011.06.005
61. Que, Y. A., Haefliger, J. A., Francioli, P., and Moreillon, P. (2000). Expression of Staphylococcus aureus clumping factor a in Lactococcus lactis subsp. cremoris using a new shuttle vector. Infect. Immun. 68, 3516-3522. doi: 10.1128/IAI.68.6.3516-3522.2000
62. Rezende, R. M., Oliveira, R. P., Medeiros, S. R., Gomes-Santos, A. C., Alves, A. C., Loli, F. G., et al. (2013). Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells. J. Autoimmun. 40, 45-57. doi: 10.1016/j.jaut.2012.07.012
63. Sanders, J. W., Leenhouts, K., Burghoorn, J., Brands, J. R., Venema, G., and Kok, J. (1998). A chloride-inducible acid resistance mechanism in Lactococcus lactis and its regulation. Mol. Microbiol. 27, 299-310. doi: 10.1046/j.1365-2958.1998.00676.x
64. Sanozky-Dawes, R., Selle, K., O'Flaherty, S., Klaenhammer, T., and Barrangou, R. (2015). Occurrence and activity of a type II CRISPR-cas system in Lactobacillus gasseri. Microbiology 161, 1752-1761. doi: 10.1099/mic.0.000129
65. Saraiva, T. D. L., Morais, K., Pereira, V. B., de Azevedo, M., Rocha, C. S., Prosperi, C. C., et al. (2015). Milk fermented with a 15-lipoxygenase-1-producing Lactococcus lactis alleviates symptoms of colitis in a murine model. Curr. Pharm. Biotechnol. 16, 424-429. doi: 10.2174/1389201015666141113123502
66. Scavone, P., Miyoshi, A., Rial, A., Chabalgoity, A., Langella, P., Azevedo, V., et al. (2007). Intranasal immunisation with recombinant Lactococcus lactis displaying either anchored or secreted forms of Proteus mirabilis MrpA fimbrial protein confers specific immune response and induces a significant reduction of kidney bacterial colonisation in mi. Microbes Infect. 9, 821-828. doi: 10.1016/j.micinf.2007.02.023
67. Sheng, J., Ling, P., and Wang, F. (2015). Constructing a recombinant hyaluronic acid biosynthesis operon and producing food-grade hyaluronic acid in Lactococcus lactis. J. Ind. Microbiol. Biotechnol. 42, 197-206. doi: 10.1007/s10295-014-1555-8
68. Simon, D., and Chopin, A. (1988). Construction of a vector plasnfid family and its use for molecular cloning in Streptococcus lactis. Biochimie 70, 559-566. doi: 10.1016/0300-9084(88)90093-4
69. Song, X., Huang, H., Xiong, Z., Ai, L., and Yang, S. (2017). CRISPR-Cas9D10A nickase-assisted genome editing in Lactobacillus casei. Appl. Environ. Microbiol. 83:e1259-17. doi: 10.1128/AEM.01259-17
70. Sørensen, S. J., Bailey, M., Hansen, L. H., Kroer, N., and Wuertz, S. (2005). Studying plasmid horizontal transfer in situ: a critical review. Nat. Rev. Microbiol. 3, 700-710. doi: 10.1038/nrmicro1232
71. Souza, B. M., Preisser, T. M., Pereira, V. B., Zurita-Turk, M., de Castro, C. P., da Cunha, V. P., et al. (2016). Lactococcus lactis carrying the pValac eukaryotic expression vector coding for IL-4 reduces chemically-induced intestinal inflammation by increasing the levels of IL-10-producing regulatory cells. Microb. Cell Fact. 15, 150. doi: 10.1186/s12934-016-0548-x
72. Steidler, L., Neirynck, S., Huyghebaert, N., Snoeck, V., Vermeire, A., Goddeeris, B., et al. (2003). Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat. Biotechnol. 21, 785-789. doi: 10.1038/nbt840
73. Suschak, J. J., Williams, J. A., and Schmaljohn, C. S. (2017). Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity. Hum. Vaccin. Immunother. 13, 2837-2848. doi: 10.1080/21645515.2017.1330236
74. Tao, L., Pavlova, S. I., Ji, X., Jin, L., and Spear, G. (2011). A novel plasmid for delivering genes into mammalian cells with noninvasive food and communal lactic acid bacteria. Plasmid 65, 8-14. doi: 10.1016/j.plasmid.2010.09.001
75. van de Guchte, M., Penaud, S., Grimaldi, C., Barbe, V., Bryson, K., Nicolas, P., et al. (2006). The complete genome sequence of Lactobacillus bulgaricus reveals extensive and ongoing reductive evolution. Proc. Natl. Acad. Sci. U.S.A. 103, 9274-9279. doi: 10.1073/pnas.0603024103
76. Wegmann, U., Klein, J. R., Drumm, I., Kuipers, O. P., and Henrich, B. (1999). Introduction of peptidase genes from Lactobacillus delbrueckii subsp. lactis into Lactococcus lactis and controlled expression. Appl. Environ. Microbiol. 65, 4729-4733
77. Wells, J. (2011). Mucosal vaccination and therapy with genetically modified lactic acid bacteria. Annu. Rev. Food Sci. Technol. 2, 423-445. doi: 10.1146/annurev-food-022510-133640
78. Williams, J. A. (2014). Improving DNA vaccine performance through vector design. Curr. Gene Ther. 14, 170-189. doi: 10.2174/156652321403140819122538
79. Yagnik, B., Padh, H., and Desai, P. (2016). Construction of a new shuttle vector for DNA delivery into mammalian cells using non-invasive Lactococcus lactis. Microbes Infect. 18, 237-244. doi: 10.1016/j.micinf.2015.11.006
80. Yagnik, B., Sharma, D., Padh, H., and Desai, P. (2017). Dual recombinant Lactococcus lactis for enhanced delivery of DNA vaccine reporter plasmid pPERDBY. Microbiol. Immunol. 61, 123-129. doi: 10.1111/1348-0421.12473
81. Zurita-Turk, M., Del Carmen, S., Santos, A. C. G., Pereira, V. B., Cara, D. C., Leclercq, S. Y., et al. (2014). Lactococcus lactis carrying the pValac DNA expression vector coding for IL-10 reduces inflammation in a murine model of experimental colitis. BMC Biotechnol. 14:73. doi: 10.1186/1472-6750-14-73