The Influence of Nanoparticle on Vaccine Responses against Bacterial Infection

Table 1

Applications of nanovaccine against bacterial infection.

Bacteria	Type of antigen in vaccine	Nanoparticle composition	Diseases	Outcomes	Ref.
Mycobacterium tuberculosis	Esat-6 three T cell epitopes (Esat-6/3e) and fms-like tyrosine kinase 3 ligand (FL) genes (termed Esat-6/3e-FL)	Chitosan	Tuberculosis	(i) Eliciting higher levels of IFN-γ and IL-12	[22]
				(ii) Increasing the expression levels of T-bet mRNA and protein
				(iii) Inducing a stronger Th1 response
				(iv) Remarkably increasing immunological and defensive effects
				(v) Increasing the number of CD3+ cells
Mycobacterium tuberculosis	Mycobacterium lipids	Chitosan	Tuberculosis	(i) Inducing the production of Th1 and Th2 cytokines	[23]
				(ii) Inducing the production of higher levels of IgG, IgG1, IgG2, and IgM
				(iii) Remarkably inducing the activation of γδ-T cells in the lymph nodes
				(iv) Substantially increasing CD8+ cells rather than CD4+ cells
				(v) Presence in both the lymph nodes and spleen cells
Mycobacterium tuberculosis	New DNA plasmid encoding eight HLA-A0201-restricted T-cell epitopes	Chitosan	Tuberculosis	(i) Maturation of dendritic cells (DCs)	[24]
				(ii) Inducing the secretion of high levels of IFN-γ by T cells
Vibrio cholerae	OmpW protein	Chitosan	Cholerae	(i) Increasing IgG and IgA immunoglobulins levels	[25]
Vibrio cholerae	LPS	Chitosan	Cholerae	(i) Inducing high levels of IgG and IgA antibodies in the sera and lavage fluid	[26]
Shigella flexneri	MxiH antigen	Chitosan	Shigellosis	(i) Improving the secretion of IgG and IgA	[27]
				(ii) Increasing the levels of IL-4 and IFN-γ
Entrohemorragic Esherichia coli (EHEC)	rEIT (EspA, Intimin, Tir)	Chitosan	Entrohemorragic Esherichia coli (EHEC) infections	(i) Decreasing symptoms associated with EHEC infections	[28]
				(ii) Prompting robust humoral and mucosal immune reactions
				(iii) Protecting mice from live EHEC O157 : H7
				(iv) Reducing adhesion properties of E. coli O157 : H7 in vitro
Escherichia coli O157 : H7	EspA (E), intimin (I), Tir (T) and Stx2 toxin	Chitosan	Haemorrhagic colitis (HC) and haemorrhagic uremic syndrome (HUS)	(i) Decreasing the adhesion ratio of pre-treated E. coli O157 : H7	[29]
				(ii) Significantly reducing bacterial colonization and excretion
				(iii) Inducing robust humoral and mucosal responses
Acinetobacter baumannii	Outer membrane protein	Chitosan	Nosocomial infections	(i) Increasing the concentration of cytokines (IL-2, IL-6, IFN-γ) and antibodies titer	[30]
				(ii) Increasing cellular and humoral immunogenicity and stimulating a balanced Th1/Th2 response
				(iii) Increasing total leukocytes and differential leukocytes
Campylobacter jejuni	pCAGGS-flaA	Chitosan	Traveller’s disease Guillain-Barré syndrome (GBS)	(i) Improving serum levels of anti-C. jejuni IgG and intestinal mucosal IgA antibodies	[31]
				(ii) Declining bacterial expulsion
Salmonella	Outer membrane proteins (OMPs) and flagellin (F) protein	Chitosan	Salmonellosis	(i) Upregulating TLRs, and Th1 and Th2 cytokines mRNA expression	[32]
				(ii) Improving immune reactions, systemic IgY and mucosal IgA antibodies reaction in chickens
				(iii) Decreasing problems associated with Salmonella load in vaccinated chickens
Salmonella enterica serovar enteritidis	Outer membrane proteins (OMP) and flagellin (FLA)	Chitosan	Salmonellosis	(i) Inducing substantial immune responses	[33]
				(ii) Ag-specific splenocyte multiplication
				(iii) Improving systemic antibody response and the frequency of IFNγ-producing T cells
				(iv) Upregulating mRNA levels of TLR 2 and TLR 4 as well as IL-4 and IL-10 cytokines
Chlamydia trachomatis	Recombinant MOMP DNA (DMOMP)	Chitosan	Sexually transmitted infection	(i) Improving in vivo presentation and expression of DMOMP in mice	[34]
				(ii) Stabilizing and protecting against enzymatic digestion
Clostridium tetani	Tetanus toxoid (TT)	PEG-PLA	Tetanus	(i) Inducing a long-lasting antibody (IgA, IgG levels) response	[35]
Chlamydia trachomatis	A peptide obtained from the recombinant major outer membrane protein (rMOMP) of Chlamydia trachomatis	PLGA	Sexually transmitted disease	(i) Increasing CD4+ and CD8+ T cells number	[36]
				(ii) Inducing higher serum levels of IgG, IgG2a (Th1), and IgG1 (Th2)
				(iii) Increasing CD4+ and CD8+ T cell subsets number
				(iv) Inducing more cytokines and chemokines: rMOMP-specific interferon-gamma (Th1) and interleukin (IL)-12p40 (Th1/Th17) than IL-4 and IL-10 (Th2) cytokines
Group A Streptococcus	A vaccine candidate based on lipopeptide (LCP-1)	PLGA	Group A Streptococcus (GAS) infections	(i) Enhancing antigen trapping and APCs	[37]
				(ii) Maturation
				(iii) Improving the levels of J14-specific salivary mucosal IgA and systemic IgG antibodies titers
Pseudomonas aeruginosa	Detoxified LPS (D-LPS)	PLGA	Nosocomial infections	(i) Stimulating humoral immune response	[38]
				(ii) Declining the spread and proliferation of bacteria and killing opsonized bacteria
Bacillus anthracis	Protective antigen domain 4 (PAD4)	PLGA	Anthrax	(i) Increasing IgG1 and IgG2a responses	[39]
				(ii) Producing a Th1/Th2 response and a Th2 response by PAD4
				(iii) Producing high levels of IL-4 and IFN-γ
Brucella melitensis	Oligopolysaccharide (OPS)	PLGA	Fever of Malta	(i) Elevating the total IgG and IgM antibody titers	[40]
				(ii) Stimulating well-ordered opsonophagocytosis of Brucella
				(iii) Exhibiting a high level of protection in challenge assay compared to other groups
Pseudomonas aeruginosa	Exotoxin A	PLGA	Cystic fibrosis	(i) Adequate immunogens for inducing humoral and cellular immunogenicity	[41]
				(ii) Reducing bacterial load in the spleens after challenge
				(iii) Substantially inducing higher secretion of INF-γ, TNF-α, IL-4, and IL-17A cytokines as well as IgG responses
Brucella abortus	rL7/L12 ribosomal protein	PLGA	Brucellosis	(i) Producing particular Brucella Ag-specific humoral and cellular reactions	[42]
				(ii) Inducing high IgG antibody titers, IgG1 as the predominant subclass
				(iii) Identifying a mixed Th1/Th2 response based on IgG1/2a ratio
				(iv) Recording Th1 cytokines particularly IFN-γ
				(v) Stimulating inflammatory responses necessary for combating Brucella infection
				(vi) Decreasing CFU of splenic bacteria
Burkholderia Cenocepacia	OMP antigen derived	Nanoemulsion	Cystic fibrosis	(i) Inducing the secretion of higher levels of IgG and mucosal IgA	[43]
Bacillus anthracis	Recombinant Bacillus anthracis protective antigen (rPA)	Nanoemulsion	Anthrax	(i) Secreting high serum levels of antibodies neutralizing lethal toxin in mice and guinea	[44]
				(ii) Elevating the expression of IFN-γ, TNF-α, and IL-2
				(iii) rPA-NE based antigen-specific Th1-type polarization of cellular responses
				(iv) Eliciting high serum levels of anti-PA IgG and bronchial anti-PA IgA. (IgG2a and IgG2b were more than IgG1)
Group A Streptococcus	Lipid-core peptide-1	Nanoliposome	GAS infections	(i) Inducing higher titers of Ag-specific mucosal IgA and systemic IgG	[45]
Helicobacter pylori	Fusion peptide CtUBE of cholera toxin B subunit and Helicobacter pylori urease B subunit epitope	Liposome	H. pylori infection	(i) Elevating the serum levels of specific anti-urease IgG and mucosal IgA	[46]
				(ii) Elevating the levels of IFN-γ
Avian pathogenic Escherichia coli (APEC)	Inactivated avian pathogenic E. coli vaccine (APEC)	Liposome	Avian colibacillosis	(i) Elevating mucosal and serum antibodies	[47]
				(ii) Decreasing bacteria in blood
Group A streptococcus	Lipopeptide	Liposome	GAS infections	(i) Mediating both mucosal and systemic immunity, IgA and IgG (IgG1 and IgG2a)	[48]
				(ii) Inducing prolonged immunity with high levels of antibodies (IgA and IgG) detected even five months’ postvaccination
Yersinia pestis	Formaldehyde-killed whole cell KWC Y. pestis	Liposome	Plague	(i) Increasing IgA and IgG levels in mucosal secretions	[49]
				(ii) Increasing specific cells secreting antibody in the lungs
				(iii) Increasing Ag-specific proliferative responses and IFN-γ-producing cells
				(iv) Improving the spleens of mice immunized against an intranasal Y. pestis challenge
Enterohemorrhagic Escherichia coli (EHEC)	Putative outer membrane protein (LomW) and (EscC) structural type III secretion system protein	Gold nanoparticles	Enterohemorrhagic infection	(i) Elevating IgG and IgA titers in serum and feces, respectively	[50]
				(ii) Decreasing the attachment to human intestinal epithelial cells
				(iii) Inducing Ag-specific bactericidal properties in serum, engaging the classical complement pathway
Francisella tularensis	Glycosylated protein complex	Gold nanoparticles	Tularemia	(i) Increasing the protection and high specific antibodies titers	[51]
Burkholderia mallei	B. thailandensis E264 lipopolysaccharide (LPS) with Hc fragment of tetanus toxin	Gold nanoparticles	Glanders	(i) Increasing the secretion of IgG1, IgG2a, and IgM in mice combating with B. mallei	[52]
				(ii) Enhancing exposure of LPS to B memory cells
Clostridium tetani	Tetanus toxoid	Gold nanoparticles	Tetanus	(i) Significantly inducing higher mucosal response following oral administration	[53]
Clostridium botulinum	Recombinant binding domain BoNT/E	Gold nanoparticles	Botulism	(i) Inducing high titers of antibody and immune response	[54]
Pseudomonas aeruginosa	N-terminal domains of P. aeruginosa flagellin	Gold nanoparticles	Nosocomial infections	(i) Eliciting higher titers of anti-flagellin (1–161) antibodies	[55]
Staphylococcus aureus	Bacterial extracellular vesicles (EVs) coating indocyanine green (ICG)	MSN	S. aureus infections	(i) Stimulating DCs maturity and enhancing the proteasome-dependent antigen presenting pathway through simplifying endolysosomal escape, promoting proteasome activity, and upregulating MHC-I expression	[56]
				(ii) Promoting CD8+ T cell responses while promoting CD4+ T cell responses and humoral immunity
				(iii) Facilitating vaccine delivery from the injection site into lymph nodes
Vibrio cholerae	Recombinant cholera toxin subunit B	MSN	Cholerae	(i) Significantly inducing mucosal immune responses	[57]
				(ii) Inducing more efficiently whole immune responses in challenge trials
Mycobacterium avium subsp. paratuberculosis	Whole cell lysate (PAN-Lysate) and culture filtrate (PAN-Cf) of M. paratuberculosis	Polyanhydride nanoparticles (PAN)	Johne’s disease (JD)	(i) Elevating the levels of Ag-specific T cell responses postimmunization	[58]
				(ii) Increasing the number of CD8+ T cells secreting cytokines (IFN-γ, IL-2, TNF-α)
Salmonella enterica serovar enteritidis	Outer membrane proteins (OMPs) and flagellar (F) protein	Polyanhydride nanoparticle (PAN)	Salmonellosis	(i) Eliciting OMPs-specific IgG responses and the production of Th1 cytokine IFN-γ in the serum	[59]
				(ii) Increasing CD8+/CD4+ cell ratio in the spleen, promoting OMPs-specific lymphocyte multiplication
				(iii) Increasing the genes expression of TLR2 and -4, TGF-β, and IL-4 cytokines
Streptococcus pneumoniae	Pneumococcal surface protein A (PspA)	Polyanhydride nanoparticle (PAN)	Pneumonia	(i) Inducing an anti-PspA antibody with high titer and high avidity	[60]