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. 2023 Aug 2;11(8):1988. doi: 10.3390/microorganisms11081988

Table 1.

Polymeric particulate TB vaccines and the immune response induced in vivo.

Particulate System Vaccine
Formulation
(Antigen/Adjuvant)		 Scheme of Immunization (Model/Route/Dose) Immune Response Induced Ref
NATURAL POLYMERS Chitosan NPs
Encapsulation 		pDNA encoding Ag 85B
No extra adjuvant		 BALB/c mice
50 μg
SC, 1× at day 0
IN, 2× at 2w interval
  • -

    Higher levels of Ag-specific IgG and IgG2a

  • -

    Enhanced proliferation of CD4+ T cells

  • -

    Higher release of IFN-γ and IL-2 in splenocytes restimulated with Ag 85B

  • -

    Induction of autophagy

 [79]
Chitosan NPs
Mix 		ESAT-6 (1–20 peptide)
A: MPL		 C57BL/6J, IFN-γ−/− and IL-17−/− mice
133 μg/50 μg
IN, 3× at 2w interval
  • -

    Potent induction of Th17 in lung and Th1/Th17 in spleen

  • -

    Higher protection against Mtb infection

  • -

    Induction of NLRP3-independent inflammasome and IL-1β

 [80]
Chitosan NPs
Coating 		Mtb cell wall lipids
No extra adjuvant		 BALB/c mice
0.5 mg/kg
SC, 1×
IP, 4× 0, 21, 45, 66 days
  • -

    Higher levels of Th1 (IFN-γ, IL-2, TNF-α) and Th2 cytokines (IL-4, IL-5, IL-13) in LNs and spleen

  • -

    γδ T-cell activation in LNs

  • -

    Higher levels of IgG, IgG1, IgG2, and IgM

 [81]
Inulin chitosan NPs
Conjugation 		Fusion
CT (CFP10-TB10.4)
No extra adjuvant		 C57BL/6 mice
100 μg/mL
SC, 3× 0, 14, 28 days
  • -

    Higher release of IFN-γ, TNF-α, IL-2, and IL-4 in splenocytes restimulated with CT

  • -

    Higher levels of CT-specific IgG1 and IgG2b

 [82]
Advax™
(δ-Inulin-NPs)
Mix 		Fusion
CysVac2 (Ag85B-CysD)
A: Advax CpG		 C57BL/6 mice
3 μg of fusion/mg inulin
IM, 3× at 2w interval
  • -

    Induction of specific multifunctional CD4+ T cells (IFN-γ+, TNF+, IL-2+)

  • -

    Reduction in CFU in lung after Mtb infection

  • -

    Strong immunogenicity and protection

 [67]
Advax™
(δ-Inulin-NPs)
Mix 		Fusion
CysVac2 (Ag85B-CysD)
A: Advax		 C57BL/6 mice
3 μg of fusion/mg inulin
IT, 3× at 2w interval
  • -

    Induction of lung-resident antigen-specific IL17-secreting CD4+ cells

  • -

    Higher protection against Mtb infection compared with BCG-vaccinated mice

 [63]
INU/pArg NCs
Adsorption 		Fusion
ECH (ESAT6/CFP-10)
A: Imiquimod 		C57BL/6 mice
10 μg of fusion
IN, 3×
  • -

    Higher levels of IgA in bronchoalveolar fluid

  • -

    Higher titers of IgG in sera

  • -

    Higher release of IFN-γ and IL-17 in splenocytes restimulated with ECH

 [83]
Dextran NPs
Immobilization 		Fusion
GamTBvac (Ag85A-ESAT6-CFP10-DBD)
A: DEAE-dextran-CpG		 C57BL/6 mice and guinea pigs
5, 10, 20 μg of fusion
SC, 2× at 3w interval		 As booster of BCG vaccine in mice:
  • -

    Higher levels of IFN-γ and Ag-specific IgG

  • -

    Reduction in CFU in lung

  • -

    Higher survival

[68]
SYNTHETIC POLYMERS PLGA NPs Encapsulation Fusion
HspX/EsxS
A: DOTAP		 BALB/c mice
25 μg of fusion/5 mg NPs
SC, 3× at 2w interval
  • -

    Higher levels of IFN-γ

  • -

    Higher titers of specific IgG1 and IgG2a compared with BCG

 [84]
PLGA NPs
Encapsulation 		Plasmid pcDNA3.1/Mtb72F
A: TB10.4 and/or CpG		 BALB/c mice
SC, 1× BCG or plasmid at day 0
SC, 3× 7, 14, 21 days		 As booster of BCG vaccine:
  • -

    Higher levels of IFN-γ in splenocytes restimulated with BCG

 [85]
Polyester NPs
Coating 		Fusion
H28 (Ag85B-TB10.4-Rv2660c)
H4 (Ag85B-TB10.4)
A: DDA		 C57BL/6 mice
2–10 μg of fusion
SC, 3× at 9-day intervals		 PNPs-H4 induced:
  • -

    Long-lasting antigen-specific T-cell responses

  • -

    Protective immunity in infected mice

  • -

    Reduction in CFU in lung

  • -

    Similar protective immunity to BCG

 [43]

NPs: nanoparticles; INU/pArgNCs: inulin/polyarginine nanocapsules; PLGA: poly(lactide-co-glycolide); A: adjuvant; MPL: monophosphoryl lipid A; DEAE: diethylaminoethyl; DOTAP: 1,2-dioleoyl-3-trimethylammonium propane; DDA: dimethyldioctadecyl ammonium bromide; SC: subcutaneous; IN: intranasal; IM: intramuscular; IP: intraperitoneal; IT: intratracheal; LNs: lymph nodes.