. 2021 Jul 17;176:113867. doi: 10.1016/j.addr.2021.113867

Table 3.

Effect of vaccines with delivery systems against different bacterial challenges.

Pathogenic bacteria	Delivery system	Antigen(s)	Adjuvants used	Route	Animal species	Protection after challenge	Ref.
B. anthracis	Adenovirus	PAD4	—	i.m.	Mice	100% of animals surviving after single immunization	[153]
	SFV	PA	—	s.c.	Mice	100% of animals surviving	[154]
	FHV VLP	PA	—	s.c.	Rats	100% of animals surviving after single immunization	[155]
	Bacteriophage T4 nanoparticle	PA	—	i.m.	Mice, rats, and rabbits	100% of animals surviving	[156]
	Live influenza virus prime and killed RV vector or the vaccinia virus vector boost	PA	—	i.n. prime and i.m boost	Mice	No results	[157]
	TMV	PA_232–247 and PA_628–637	—	i.p.	Mice	Almost no protection	[158]
	Liposomes	PA	Monophosphoryl lipid A	i.m.	Rabbits and rhesus macaques	100% of animals surviving	[159], [160]
	Liposome-like vessels	PAD4	Aluminium hydroxide	i.p.	Mice	70% of animals surviving	[161]
	FUC-HTCC NPs	Anthrax vaccine AVA	—	i.p.	Mice	100% of animals surviving	[162]
	Chitosan	PA	C48/80	i.n.	Mice	No results	[163]
	Chitosan derivative TMC	PA	CpG or Poly I:C or not	s.c.^a, i.m.^a, or i.p.	Mice	83.3% of animals surviving in s.c. or i.m. route	[164]
	CS-NH2 microparticles	PA	—	s.c.	Mice	No results	[165]
	Poly-l-lactide (PLLA) polylactide (PLA) microspheres	PA	—	i.m prime and either i.m. or i.n. boost	Mice	100% of animals surviving	[166]
	Dendriplex PLGA nanoparticles	PA (DNA)	—	i.m.	Mice	High antibody titer but without neutralizing activity	[167]
	PLGA nanoparticles	PAD4	—	i.p.	Mice	11% of animals surviving after single immunization	[168]
	sucrose polymer Ficoll	PA	CpG-ODN	i.m.	Mice	100% of animals surviving after single immunization	[169]
	Soybean oil-and-water nanoemulsion (NE)	PA	—	i.n.	Mice and guinea pigs	100% of animals surviving	[170]
	L. acidophilus	PA(Surface)^b	—	No results	No	No results	[171]
	L. casei	PA^b	—	Oral or i.n.	Mice	No results	[172]
	L. acidophilus	PA with DC-targeting peptide (Secretory)^b	—	Oral	Mice	75% of animals surviving	[173]
	L. gasseri	PA with DC-targeting peptide (Secretory)^b	—	Oral	Mice	100% of animals surviving and 30% of animals surviving without DC-targeting peptide	[174], [175]
	S. enterica	PA, PAD1 and 4, and PAD4	—	Oral	Mice	PA: 83% of animals surviving, PAD1 and 4: 25% of animals surviving, PAD4: no protection	[176]

Neisseria meningitidis group B	E. coli OMV	Glycan antigens (Polysialic acid (PSA) and T antigen)	—	s.c.	Mice	50% SBA was observed at over 100-fold dilutions of the serum	[177]
Brucella	SFV	Cu-Zn SOD	—	i.p.	Mice	1.52 (3.07–1.55)^c	[178]
		IF3	—	i.p.	Mice	1.09 (6.96–5.87)^c	[179]
	Influenza virus	L7/L12 or Omp16	—	i.n., eyedrop^a, or s.c.	Mice	The best: Omp: 16: 3.78 (4.54–0.76)^c, eyedrop; Bivalent: 3.9 (4.54–0.64)^c, eyedrop	[180]
	Influenza virus	Tetravalent vaccine formulation expressing Omp16, L7/L12, Omp19, and Cu-Zn SOD	—	i.n.^a, eyedrop, or s.l.	Guinea pigs	The best: 2.8 (2.86–0.06)^c, i.n.	[181]
	L. lactis	L7/L12 (Cytoplasm)^b	—	Oral	Mice	0.57 (7–6.43)^c	[182]
		Cu-Zn SOD (secretory)^b	—	Oral	Mice	1.35 (7.1–5.75)^c	[183]
	L. lactis (Live or killed)	Omp31 (Cell Wall-Anchored)^b	—	Oral or i.p.	Mice	No results	[184]
	Attenuated S. typhimurium	Fusion of L7/L12 and BLS^b	—	Oral	Mice	Secretory expression: 1.55 (4.44–2.89)^c; Intracellular expression: 1.32 (4.44–3.12)^c	[185]
		L7/L12	—	i.m.	Mice	About 1.7 (3.4–1.7)^c	[186]
	Ochrobactrum anthropi	Cu-Zn SOD	CpG	i.p.	Mice	2.42 (5.30–2.88)^c	[187]
	TMC	Omp19	—	Oral^a or i.p.	Mice	The best: against B. abortus: 2.46 (6.3–3.84)^c, oral; against B. melitensis: 2.38 (6.14–3.76)^c, oral	[188]
	Mannosylated chitosan nanoparticles	FliC	—	s.c.	Mice	Against B. melitensis: 1.34 (5.67–4.33)^c; against B. abortus: 1.22 (5.24–4.02)^c	[189]
	escheriosome	L7/L12	—	s.c.	Mice	1.46 (4.58–2.93)^c	[190]
		Cu-Zn SOD	IL-18	s.c.	Mice	1.5 (5.2–3.7)^c	[191]
	PLGA	L7/L12	—	i.p.	Mice	1.79 (5.94–4.15)^c	[192]
	CaPNs	FliC, 7α-HSDH, BhuA and multi-epitopes (Poly B and poly T)	—	s.c.	Mice	The best: against B. melitensis: Poly B + T, 1.5 (5.77–4.27)^c; against B. abortus: Poly B + T, 1.37 (5.29–3.92)^c	[193]

S. aureus	OMV (E. coli)	Hla_H35L, SpA_KKAA, FhuD2, Csa1A, and LukE	Alum	i.p.	Mice	90% of animals surviving	[194]
	PDNVs (E. coli)	SAcoagulase	—	i.p.	Mice	100% of animals surviving	[195]
	extracellular vesicles (EVs)	Hla_H35L, LukE and EVs components	—	s.c.	Mice	About 70% and 50% of animals surviving after challenging with two S. aureus isolates	[196]
	ICG-loaded MSNs	EVs	—	s.c.	Mice	Decreased bacterial loading in skin and organs	[197]
	PDNVs	PDNVs components	—	s.c.	Mice	No results	[198]
	L. lactis	ClfA^b and FnbpA^b	Freund’s adjuvant	Unknown	Rats	Less infected vegetations after challenging with S. aureus Newman in L. lactis ClfA-immunized animals; FnbpA did not have the same effect	[199]
	PilVax	B-cell epitope, D3, from FnbpA	—	i.n.	Mice	Decreased bacterial loading in intestine and nasal mucosa	[200]
	Cowpea mosaic virus	D2 domain of FnbpB	—	i.n. or oral	Mice	No results	[201]
	Live attenuated S. typhimurium	SaEsxA^b and SaEsxB^b	—	Oral	Mice	22.2% and 44.4% of animals surviving after challenging with S. aureus USA 300 for SaEsxA and SaEsxB; no animals surviving after challenging with S. aureus Newman	[202]
	Red blood cell membrane-coated PLGA	Hla, α-toxin, PVL, and γ-toxin	—	s.c.	Mice	Decreased bacterial loading in skin, blood, and organs	[203], [204]
	PP7 (VLP)	AIP1S	—	i.m.	Mice	Inhibiting abscess area and dermonecrotic; Decreased bacterial loading at the site of infection	[205]
	PLGA	CNA19	—	s.c. or i.n.	Mice	No results	[206], [207]
	PLGA	rSEA	—	i.p.	Mice	100% of animals surviving	[208]
	Chitosan	rSEB	—	i.n.		No results	[209]
	Chitosan	Ami		No results	No results	No results	[210]
	Liposome	AdsA (mRNA)	—	i.m. or s.c.	Mice	No results	[211]

H. pylori	L. lactis (GEM)	CUE	—	Oral	Mice	Decreased bacterial loading in gastric tissue	[212], [213]
	L. acidophilus	Hp0410	—	Oral	Mice	Decreased bacterial loading in gastric tissue	[214]
	L. plantarum	Urease Bsubunit (UreB) (Cytoplasm)^b	—	Oral	Mice	Decreased bacterial loading in gastric tissue	[215]
	HP55/PLGA nanoparticles	Recombinant antigen CCF	—	Oral	Mice	Decreased bacterial loading in gastric tissue	[216]
	OMVs	OMV components	—	Oral	Mice	Decreased bacterial loading in gastric tissue	[217]
	liposomes	Fusion of the urease linear epitope (19 amino acid residues) and CTB	—	Oral	Mice	Decreased bacterial loading in gastric tissue	[218]

Yersinia pestis	Bacteriophage T4 nanoparticles	Mutated capsular antigen F1 and low-calcium-response V antigen	—	i.m.	Rats	100% of animals surviving	[155]
	20:80 CPTEG:CPH	Fusion of F1 and V antigens	Cyclic dinucleotides (CDNs)	s.c.	Mice	100% of animals surviving at 14 days and 75% at 182 days after single immunization	[219]
	OMVs	OMV components	—	i.m.	Mice	100% of animals surviving in subcutaneous challenge; 100% and 50% of animals surviving in intranasal challenge with a median and a high dose	[220]
	L. plantarum	LcrV (Surface)^b	—	Oral	Mice	No results	[221]

a. The better or the best route to achieve protection; b. Constructed in an expression vector; c. Log₁₀ units of protection, obtained by subtracting the mean log₁₀CFU for the experimental group from the mean log₁₀ CFU for the corresponding control group; i.n., intranasal; s.c., subcutaneous; i.m., intramuscular; i.p., intraperitoneal; s.l., sublingual; —, without added adjuvant.