11. The animal restraint is usually done with the nondominant
hand so that the dominant hand is free to do more precisionrequired procedures such as anesthetic injection and gavage.
12. The lower right quadrant of the abdomen is chosen as the
intraperitoneal space because it has less organs and also to
avoid cecum perforation.
References
1. Bermu ´ dez-Humara ´n LG, Aubry C, Motta J-P
et al (2013) Engineering lactococci and lactobacilli for human health. Curr Opin Microbiol
16:278–283. https://doi.org/10.1016/j.mib.
2013.06.002
2. Bermu ´ dez-Humara ´n LG (2009) Lactococcus
lactis as a live vector for mucosal delivery of
therapeutic proteins. Hum Vaccin 5
(4):264–267
3. Souza BM, Preisser TM, Pereira VB 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 Factories
15:150. https://doi.org/10.1186/s12934016-0548-x
4. Mancha-Agresti P, Drumond MM, FLR do C
et al (2017) 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. https://doi.
org/10.1016/j.omtm.2016.12.005
5. Coelho-Rocha ND, de Castro CP, de Jesus
LCL et al (2018) Microencapsulation of lactic
acid Bacteria improves the gastrointestinal
delivery and in situ expression of recombinant
fluorescent protein. Front Microbiol 9:2398.
https://doi.org/10.3389/fmicb.2018.02398
6. Pontes DS, De Azevedo MSP, Chatel JM et al
(2011) Lactococcus lactis as a live vector: heterologous protein production and DNA delivery systems. Protein Expr Purif 79:165
7. Fioretti D, Iurescia S, Fazio VM, Rinaldi M
(2010) DNA vaccines: developing new strategies against cancer. J Biomed Biotechnol
2010:174378
8. Myhr AI (2017) DNA vaccines: regulatory
considerations and safety aspects. Curr Issues
Mol Biol 22:79–88. https://doi.org/10.
21775/cimb.022.079
9. Babiuk LA, Pontarollo R, Babiuk S et al (2003)
Induction of immune responses by DNA vaccines in large animals. Vaccine 21:649. https://
doi.org/10.1016/S0264-410X(02)00574-1
10. Ferraro B, Morrow MP, Hutnick NA et al
(2011) Clinical applications of DNA vaccines:
current progress. Clin Infect Dis 53:296–302.
https://doi.org/10.1093/cid/cir334
11. Roy MJ, Wu MS, Barr LJ et al (2000) Induction of antigen-specific CD8+ T cells, T helper
cells, and protective levels of antibody in
humans by particle-mediated administration
of a hepatitis B virus DNA vaccine. Vaccine
19:764.
https://doi.org/10.1016/S0264410X(00)00302-9
12. Wang B, Boyer J, Srikantan V et al (1993) DNA
inoculation induces neutralizing immune
responses against human immunodeficiency
virus type 1 in mice and nonhuman primates.
DNA Cell Biol 12:799. https://doi.org/10.
1089/dna.1993.12.799
13. Kutzler MA, Weiner DB (2008) DNA vaccines:
ready for prime time? Nat Rev Genet
9:776–788.
https://doi.org/10.1038/
nrg2432
14. Neutra MR, Kozlowski PA (2006) Mucosal
vaccines: the promise and the challenge. Nat
Rev Immunol 6:148–158. https://doi.org/
10.1038/nri1777
15. Machholz E, Mulder G, Ruiz C et al (2012)
Manual restraint and common compound
administration routes in mice and rats. J Vis
Exp (67). https://doi.org/10.3791/2771
16. Song J-H, Nguyen HH, Cuburu N et al
(2008) Sublingual vaccination with influenza
virus protects mice against lethal viral infection.
Proc Natl Acad Sci U S A 105:1644. https://
doi.org/10.1073/pnas.0708684105
Lactic Acid Bacteria for Therapeutic Applications
459
hand so that the dominant hand is free to do more precisionrequired procedures such as anesthetic injection and gavage.
12. The lower right quadrant of the abdomen is chosen as the
intraperitoneal space because it has less organs and also to
avoid cecum perforation.
References
1. Bermu ´ dez-Humara ´n LG, Aubry C, Motta J-P
et al (2013) Engineering lactococci and lactobacilli for human health. Curr Opin Microbiol
16:278–283. https://doi.org/10.1016/j.mib.
2013.06.002
2. Bermu ´ dez-Humara ´n LG (2009) Lactococcus
lactis as a live vector for mucosal delivery of
therapeutic proteins. Hum Vaccin 5
(4):264–267
3. Souza BM, Preisser TM, Pereira VB 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 Factories
15:150. https://doi.org/10.1186/s12934016-0548-x
4. Mancha-Agresti P, Drumond MM, FLR do C
et al (2017) 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. https://doi.
org/10.1016/j.omtm.2016.12.005
5. Coelho-Rocha ND, de Castro CP, de Jesus
LCL et al (2018) Microencapsulation of lactic
acid Bacteria improves the gastrointestinal
delivery and in situ expression of recombinant
fluorescent protein. Front Microbiol 9:2398.
https://doi.org/10.3389/fmicb.2018.02398
6. Pontes DS, De Azevedo MSP, Chatel JM et al
(2011) Lactococcus lactis as a live vector: heterologous protein production and DNA delivery systems. Protein Expr Purif 79:165
7. Fioretti D, Iurescia S, Fazio VM, Rinaldi M
(2010) DNA vaccines: developing new strategies against cancer. J Biomed Biotechnol
2010:174378
8. Myhr AI (2017) DNA vaccines: regulatory
considerations and safety aspects. Curr Issues
Mol Biol 22:79–88. https://doi.org/10.
21775/cimb.022.079
9. Babiuk LA, Pontarollo R, Babiuk S et al (2003)
Induction of immune responses by DNA vaccines in large animals. Vaccine 21:649. https://
doi.org/10.1016/S0264-410X(02)00574-1
10. Ferraro B, Morrow MP, Hutnick NA et al
(2011) Clinical applications of DNA vaccines:
current progress. Clin Infect Dis 53:296–302.
https://doi.org/10.1093/cid/cir334
11. Roy MJ, Wu MS, Barr LJ et al (2000) Induction of antigen-specific CD8+ T cells, T helper
cells, and protective levels of antibody in
humans by particle-mediated administration
of a hepatitis B virus DNA vaccine. Vaccine
19:764.
https://doi.org/10.1016/S0264410X(00)00302-9
12. Wang B, Boyer J, Srikantan V et al (1993) DNA
inoculation induces neutralizing immune
responses against human immunodeficiency
virus type 1 in mice and nonhuman primates.
DNA Cell Biol 12:799. https://doi.org/10.
1089/dna.1993.12.799
13. Kutzler MA, Weiner DB (2008) DNA vaccines:
ready for prime time? Nat Rev Genet
9:776–788.
https://doi.org/10.1038/
nrg2432
14. Neutra MR, Kozlowski PA (2006) Mucosal
vaccines: the promise and the challenge. Nat
Rev Immunol 6:148–158. https://doi.org/
10.1038/nri1777
15. Machholz E, Mulder G, Ruiz C et al (2012)
Manual restraint and common compound
administration routes in mice and rats. J Vis
Exp (67). https://doi.org/10.3791/2771
16. Song J-H, Nguyen HH, Cuburu N et al
(2008) Sublingual vaccination with influenza
virus protects mice against lethal viral infection.
Proc Natl Acad Sci U S A 105:1644. https://
doi.org/10.1073/pnas.0708684105
Lactic Acid Bacteria for Therapeutic Applications
459
