TABLE 2.

The strategies applicated in LAB vaccines to augment the immune responses

Vaccine strategies	Mechanism	LAB strain	Antigen	Administration route	Immune responses	Protection
Co‐expression of targeting molecules
Dendritic cells targeting peptides and antibodies: DCpep, scFv‐CD11c, scFv‐DEC205	Promote the maturation of DCs and enhance antigen uptake by DCs.	Lactobacillus casei	E2 protein of bovine viral diarrhea virus	Oral	Serum antibody, mucosal antibody in intestinal mucus and feces, neutralizing activity and cytokines of IFN‐γ and IL‐4	Eliminate the virus from intestine, lung, blood, and spleen.[ 40 ]
		Lactobacillus plantarum	NP and M1 protein of avian influenza virus	Oral	Fecal and BALF IgA antibody and IFN‐γ‐producing T‐cells	Provide 80% and 60% protection rate against homologous and heterologous virus infection, respectively.[ 42 ]
		Lactobacillus plantarum	Hemagglutinin protein of Influenza A virus (H1N1)	Oral	Serum IgG, BALF and fecal IgA, neutralizing antibody, B220+IgA+ B cells in PP and IFN‐γ‐producing T‐cells	Increase survival of immunized mice after influenza virus challenge.[ 43 ]
M cells targeting peptides or proteins: Col, CKS9, OmpH.	Enhance the effectiveness of antigen delivery through the intestinal mucosa.	Lactobacillus saerimneri	OmpC and FimA proteins of avian pathogenic Escherichia coli	Oral	Antigen‐specific serum IgG and SIgA in cecum, nasal cavity, and feces	80% immunized chicken survived after avian E. coli challenges.[ 47 ]
		Lactococcus lactis	Viral capsid protein (VP)2 antigen of infectious bursal disease virus	Oral Intramuscular	Neutralizing antibody and mucosal SIgA antibody	Provide complete protection by injection and 80% protection rate by oral.[ 51 ]
Intestinal epithelial cells targeting proteins: FnBPA	Improve the delivery ability and increase antigen uptake by lymphocytes	Lactococcus lactis	E7 antigen of human papillomavirus16	Intranasal	IgG2a systemic and IgA mucosal immune responses and CTL	Reduce tumor development.[ 56 ]
Cytokines
IL‐12	Stimulate activity of cytotoxic T lymphocytes and natural killer (NK)‐cells; promote IFN‐γ production.[ 57 ]	Lactococcus lactis	E7 antigen of human papillomavirus16	Intranasal	ELISPOT: IFN‐γ‐secreting T‐cells[ ]; E7‐specific CTL response, cytokines of IL‐12 and IFN‐γ[ 59 ]	Increase survival rates and regress tumor growth.[ 58 , 59 ]
		Lactococcus lactis	Leishmania antigen LACK	Oral	IgA antibodies in intestinal washes and a systemic Th1 immune response	No report[ 60 ]
IL‐2	Induce the proliferation of immune cells and the differentiation of effector CD4+T cells.[ 63 ]	Lactococcus lactis	UreB protein of Helicobacter pylori	Oral	Serum antibody, fecal IgA and serum IFN‐γ, IL‐4, and IL‐17	Accelerate H. pylori clearance and reduce the levels of H. pylori colonization in the stomach.[ 65 ]
IL‐6	Promote the secretion of antibodies by maturated B cells and the production of IL‐2.[ 68 ]	Lactococcus lactis	Tetanus toxin fragment C	Intranasal	anti‐TTFC IgG and IgA responses	No report[ 69 ]
		Lactococcus lactis	Brachyspira membrane protein B	Oral	Serum IgG, IgG1, and IgG2a, feces and intestinal IgA, IL‐4, IFN‐γ, and IL‐2‐secreting lymphocytes in PPs	No report[ 49 ]
Mucosal adjuvant
Cholera toxin	Induce the polarization of T cells towards Th2 and B cells activated and isotype switching.	Lactococcus lactis	Influenza virus nucleoprotein	Oral	Serum antibody, mucosal IgA in intestine and upper respiratory washes, and IFN‐γ and IL‐4 secreting splenocytes	Improve the resistance to divergent influenza viruses challenge.[ 74 ]
		Lactobacillus casei	Matrix protein‐2 of influenza virus	Oral Intranasal	Serum IgG, IgA antibody in lung and intestine, and IFN‐γ and IL‐4 secreting splenocytes	Decrease virus titers in the lung tissues after challenge with influenza virus.[ 76 ]
Heat‐labile enterotoxin	Induces mixed Th1 and Th2 immune responses and B cells and DCs activation.	Lactobacillus casei	VP4 antigen of porcine rotavirus	Oral	Serum IgG, specific IgA in ophthalmic, vaginal wash and feces, neutralization activity	No report[ 80 ]
		Lactobacillus casei	F4 (K88) fimbrial adhesin FaeG of enterotoxigenic Escherichia coli	Oral	SIgA in feces, vaginal lavage, and nasal lavage, serum antibody, and lymphocyte proliferation	Provide complete protection to immunized mice.[ 83 ]
Flagellin	Toll‐like receptor 5 agonist, stimulate the activation of NF‐kB, the maturation of DCs[ 85 ]	Lactobacillus acidophilus	Gag protein of HIV‐1	Oral	IgA‐secreting and IFN‐γ‐producing lymphocytes from Peyer's patches, female reproductive tract, and large intestine	No report[ 87 ]
Polymer's coating
Enteric‐coated capsules	Improve the stability and viability of LAB in the gastrointestinal tract	Lactococcus lactis	Hemagglutinin protein of H5N1	Oral	Serum IgG and fecal IgA, IFN‐γ secreting splenocytes	Provide full immune protection against H5N1 virus challenges[ 96 ]
Alginate/chitosan/alginate microcapsules		Lactobacillus plantarum	Brachyspira membrane protein B	Oral	Serum IgG, IgG1, and IgG2a, feces, and intestinal IgA	No report[ 97 ]