Table 2.
Representative studies utilizing polymeric nanostructures for vaccine development against infectious diseases.
| Vaccine platform |
Antigen |
Adjuvant |
Admin route |
Organism model |
Humoral response |
T cell response |
Other attributes |
Ref. |
|
|---|---|---|---|---|---|---|---|---|---|
| CD4+ Th cells |
CD8+ T cells |
||||||||
| Viral Infection | |||||||||
| H5N1 avian influenza virus | |||||||||
| PLGA nanoparticle | HA | PLGA nanoparticle encapsulated MPL and R837 | s.c. | Mouse | IgG1, IgG2a, IgG2b, and virus neutralizing antibody titer | Th1 | Strong response | 100% survival and maintained body weight were achieved for 14-days post-infection. The antigen-specific memory CD4+ T cells was persistent for 1.5-year post-vaccination. | [132] |
| PA nanoparticle | H5 HA trimer | Pentablock copolymer hydrogel | s.c. | Mouse | Sustained virus neutralizing antibody titer for up to 70 days | N/E | N/E | Significant reduction of viral load in the lungs of mice, with maintained body weight similar to healthy, noninfected mice | [143] |
| H1N1 swine influenza virus | |||||||||
| PS-core protein-shell nanoparticle | HA | – | i.v. | Mouse | IgG, IgG1, IgG2a and HA inhibition titers | Th1 | Strong response with CTL activity | Protection against H1N1 virus for up to 16 days post-infection as indicated from high survival rate and minimum body-weight loss | [104] |
| pABOL nanoparticle | saRNA encoding for HA | – | i.m. | Mouse | HA IgG, HA inhibition, and virus neutralization titers | N/E | N/E | The mice were protected against the H1N1 challenge as reflected from 8% decrease of the body weight as compared to naïve mice which lost >25% of body weight | [127] |
| Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | |||||||||
| Hollow-core PLGA-shell nanoparticle coated with lipid | Receptor binding domain protein | cdGMP | s.c. | Mouse | IgG, IgG1, IgG2a (for 300 days post-vaccination), with the virus neutralizing titer | Balanced Th1/Th2, with persistent central memory CD4+ T cell responses (for 28-day) | Strong and peptide specific responses, with CTL activity | Significant reduction of virus load titers in the lungs after the challenge, with 100% survival for 24-days post-infection | [96] |
| Zika virus (ZIKV) | |||||||||
| Chitosan/γ-PGA nanoparticle | Inactivated Zika virus | – | s.c. | Mouse | IgG, IgG1, IgG2a | Balanced Th1/Th2 | Strong response | The produced antibody was able to neutralize Zika virus infection | [128] |
| Ebola virus (EBOV) | |||||||||
| PAA-PPI dendrimers and lipid-PEG nanoparticle | VEEV replicon RNA for the EBOV glycoprotein | – | i.m. | Mouse | IgG | Th1 | Strong response with the production of IFN-γ and IL2 | After 23-days post-infection, the mice immunized with a single dose of the polymeric vaccines achieved 100% survival rate | [129] |
| Dengue virus (DENV) | |||||||||
| PLGA nanoparticle | Tetravalent E protein | – | s.c. | Mouse | IgG, IgG1, IgG2a, and virus neutralizing antibody titer | Balanced Th1/Th2 | N/E | A balanced serotype-specific antibody response was stimulated to each DENV serotype (DENV1, DENV2, DENV3 and DENV4) | [130] |
| Human immunodeficiency virus (HIV) | |||||||||
| Mannosylated PEI nanoparticle | Plasmid DNA encoding 15 protein antigens | – | t.d. | Human (Phase I, Phase I/II) | – | Th1 | Strong response with the production of IFN-γ and IL2, and CTL activity | HIV-specific precursor/memory T cells with high proliferation capacity was expanded in a dose-dependent manner at week 48 post-immunization | [144,145] |
| PLGA microparticle | Plasmid DNA encoding Gag and V2-deleted gp140 Env | MF59 during boosting | i.m. | Human (Phase I) | Strong neutralization antibody against the homologous HIV, but minimal neutralization breadth against the heterologous HIV | Th1 | Minimal response | Polyfunctional CD4+ T cell responses were elicited, comprising of IFN-γ (most dominant), IL2, TNF-α and IL-4 | [135] |
| PEI-cyclodextrin nanoparticle | mRNA for gp120 glyco-protein | – | i.n. | Mouse | IgG, IgG1, IgG2a, and secreted IgA in distal mucosa | Balanced Th1/Th2/Th17 | Strong response with cytotoxic T-lymphocyte activity | The nanoparticles could facilitate antigen delivery through intra- and paracellular pathways, inducing both systemic and mucosal immune response | [92] |
| PLGA nanoparticle | HIV-1 p24-Nef fusion peptide | Recombinant FLiC protein (TLR5 agonist) | i.d. | Mouse | IgG, IgG1 and IgG2a | Th1 and Th2 | Strong response with cytotoxic T-lymphocyte activity | Lowering the immunization dose significantly increased the Th1 cytokine and slightly decreased the humoral response | [136] |
| CS/DS, or CS/HA nanoparticles | PCS5 peptide antigen | Poly(I:C) (TLR3 agonist) | i.m. | Mouse | IgG | Th1 | Strong response | Central and effector memory CD4+ and CD8+ T cells were generated | [146] |
| Hepatitis B Virus (HBV) | |||||||||
| CS/γ-PGA nanogels | HBsAg | – | i.m. | Mouse | IgG | Th2 | Strong response with induction of effector memory CD8+ T cells | Single dose vaccination of cationic CS/γ-PGA nanogels cleared HBsAg and restored IgG production after plasmid challenge | [147] |
| CS nanoparticle | HBsAg | – | i.p. | Mouse | IgG, IgG1, IgG2a, IgG2b, IgG3 titers in serum, spleen and bone marrow | Th1 and Th2 | N/E | The humoral and cellular response were durable up to 30-weeks after single-dose vaccination, with increased in BAFF-R + B cells, CD138+ plasma cells, and Tfh cells | [133] |
| PLA-core lipid-shell microparticle | HBsAg | – | i.m. | Mouse | IgM, IgG, IgG1 and IgG2a | Th1 | Strong response with CTL activity | Granzyme B, the effector of cytotoxic T cell, was also produced | [148] |
| Hepatitis C Virus (HCV) | |||||||||
| PHB-core protein-shell particle | HCV core protein | CFA or Emulsigen | s.c. | Mouse | IgG1 and IgG2c | Th1 | N/E | Strong cytokine profiles, including IFN-γ, TNF-α, IL-17A, IL-2, IL-6, and IL-10 as compared to the respective soluble controls | [149] |
| PHB-core protein-shell particle | HCV core protein | Alum | i.m. | Mouse | IgG | Th1 | N/E | Reduction of virus load titer in ovaries after the challenge | [150] |
| Bacterial infection | |||||||||
| Mycobacterium tuberculosis | |||||||||
| PEG–PPS micelle | Mycolid acid (MA) – a lipid antigen | – | i.n. | Mouse | Anti-CD1b antibody titers | Th1 | N/E | The nanoparticles were primarily taken up by alveolar macrophages and DCs in the lung | [151] |
| PHB-core protein-shell particle | Mycobacterial fusion peptides Ag85B–TB10.4–Rv2660c | DDAB | s.c. | Mouse | Antigen-specific antibody titers, dominated by IgG1 | Th1, Th2 and Th17 | N/E | Strong production of cytokines, IFN-γ, TNF-α, IL-17A, IL-2, IL-6, IL-10, as compared to the respective soluble controls | [131] |
| Mycobacterium paratuberculosis | |||||||||
| PA nanoparticle | M. paratuberculosis culture filtrate | – | s.c. | Mouse | N/E | Th1 | Strong responses both post-vaccination and post-challenge | The bacterial load in spleen, liver, small intestine and mesenteric lymph node was reduced. | [152] |
| Mycobacterium bovis | |||||||||
| PHB-core protein-shell particle | Mycobacterial fusion proteins, Ag85A–ESAT-6 | Emulsigen | s.c. | Mouse | IgG | Th1 and Th17 | N/E | Reduction of bacterial count in the spleen and the lung after the challenge | [153] |
| Staphylococcus aureus (resistant to the antibiotic, methicillin) | |||||||||
| PLGA-core red blood cell-shell nanoparticle | α-hemolysin (Hla) protein | – | s.c. | Mouse | Anti-Hla IgG titer for up to 35 days, with germinal center formed | N/E | N/E | Minimum skin lesion area and reduced bacterial load in the skin. Reduced bacterial load was also observed in major organs (heart, kidney, spleen, lung and liver) after the challenge | [154] |
| PLGA-core red blood cell-shell nanoparticle | Combination of α-toxin, PVL, and γ-toxin | – | s.c. | Mouse | Anti-α-toxin, anti-PVL, and anti γ-toxin, with germinal center formed | N/E | N/E | Minimum skin lesion area, and reduced bacterial load at heart, lung and kidney after the challenge | [155] |
| Pseudomonas aeruginosa | |||||||||
| PLGA-core macrophage-shell nanoparticle | Combination of FliC, OprM, OprE and SSB | – | s.c. and i.n. | Mouse | IgG, with germinal center formed. | N/E | N/E | After i.n. injection, both systemic and mucosal immunities were elicited. Reduced bacterial load in lung for both s.c. or i.n. vaccination. | [138] |
| PHB-core protein-shell particle | Fusion antigenic epitopes AlgE, OprF and OprI | Alum | s.c. | Mouse | IgG1 and IgG2c, with opsonophagocytic antibody titer | Th1 | N/E | Without the adjuvant, Th1 immune response can be induced | [156] |
| Streptococcus pneumoniae | |||||||||
| cCHP nanogel | PspA | – | i.n. | Rhesus Macaque | PspA-specific bronchoalveolar fluid IgG and nasal wash IgA antibodies, with neutralizing antibody titer | Th2 and Th17 | N/E | The mice injected intraperitoneally with the pooled sera of macaques nasally immunized with the nanogels were protected from the challenge for at least 2 weeks | [157] |
| PHB-core protein-shell particle | Ply and 19F CPS | – | s.c. | Mouse | IgG with the dominant IgG1 and IgG2b, and opsonophagocy-tic antibody titer | Th2 | N/E | The IgG was persistent for up to 6 months and recognized Ply in whole cell lysates of six different S. pneumoniae serotypes | [158] |
| PHB-core protein-shell particle | PsaA | – | s.c. | Mouse | IgG with the dominant IgG1 and IgG2b | Th2 | N/E | The elicited IgG recognized PsaA in whole cell lysate of seven different serotypes of S. pneumoniae | [159] |
| Neisseria meningtidis | |||||||||
| PHB-core protein-shell particle | NadA and MenC | – | s.c. | Mouse | IgG with the dominant IgG1 and IgG2b | Th1 and Th17 | N/E | The serum exhibited bactericidal activity | [160] |
| Parasitic infection | |||||||||
| Plasmodium yoelii | |||||||||
| PS nanoparticle | MSP 4/5 | – | i.d. | Mouse | IgG, IgG1, IgG2a, IgG2b | Th1 and Th2 | N/E | Moderate survival rate of the immunized mice against the blood-stage malaria infection was demonstrated | [161] |
| Plasmodium falciparum | |||||||||
| PLGA nanoparticle | Pfs25 | – | s.c. | Rhesus macaque | IgG | Th1 | Strong response | •The T cell response increased the antibodies' avidity •The numbers of Pfs25-specific plasmablasts, circulating memory B cells, and plasma cells in the bone marrow were increased. | [162] |
| Plasmodium vivax | |||||||||
| PLGA-core lipid-shell nanoparticle | VMP001 | MPLA | s.c. | Mouse | IgG, IgG1, IgG2b, IgG2c, IgG3, with germinal center formed | Balanced Th1/Th2 | N/E | The antibodies had high avidity that could agglutinate live sporozoites 6-month after the vaccination | [163] |
Abbreviation: N/E, not evaluated.
1. Vaccine platform: cCHP, cholesteryl group-bearing pullulan; CS, chitosan; DS, dextran sulfate; HA, hyaluronic acid; PA, poly(anhydride); PAA-PPI, poly(amido amine)-poly(propylenimine); pABOL, poly(N,N-cystaminebis(acrylamide)-co-4-amino-1-butanol); PAS, poly(acrylic starch); PEG, poly(ethylene glycol); PHB, poly(3-hydroxybutyric acid); PLA, poly(lactic acid); PLGA, poly(lactic-co-glycolic acid); PS, poly(styrene).
2. Antigens: CPS, capsular polysaccharide; ESAT-6, early secreted antigenic target 6-kDa protein; Flagellin, FliC; HA, hemagglutinin; HBsAg, hepatitis B surface antigen; MenC, capsular polysaccharide from serogroup C; MSP 4/5, Recombinant merozoite surface protein 4/5; M2e, matrix protein 2 ectodomain; NadA, Neisseria adhesin A; NP, nucleoprotein; OprM and OprE, Outer membrane proteins; PA, polymerase protein; PCS5, protease cleavage site 5; Pfs25, a glycophosphotidylinositol-linked protein expressed on the ookinetes surface; Ply, Pneumolysin; PsaA, Pneumococcal surface adhesin A protein; PspA, Pneumococcal surface protein A; PVL, Panton–Valentine leucocidin; saRNA, self-amplifying RNA; SSB, single-stranded DNA binding protein; VEEV replicon RNA, Venezuelan equine encephalitis virus replicon RNA; VMP001, Vivax malaria protein – a recombinant antigen derived from the circumsporozoite protein.
3. Adjuvant: cdGMP, cyclic diguanylate monophosphate; CFA: complete Freund's adjuvant; CpG ODN, CpG oligodeoxynucleotide; DDAB, dimethyl dioctadecyl ammonium bromide; MPLA, monophosphoryl lipid A; poly(I:C), polyinosinic:polycytidylic acid.
4. Route of administration: i.d., intradermal; i.m., intramuscular; i.n., intranasal; i.t., intratracheal; p.o., oral; s.c., subcutaneous; t.d., transdermal.