Table 2.
Microparticles and nanoparticles for Pneumococcal antigen delivery.
| Nanoparticles | Characteristics of Nanoparticles | Pneumococcal Strains Used in Challenge Studies | Antigen (s) | Results | References |
|---|---|---|---|---|---|
| Polylactide (PLA) | 45 kDa, 2–8 μm | n/a | PspA | The entrapment of PspA in PLA particles was observed to be stable. Polymer particles entrapping PspA elicited robust IgG responses in both mice and in rats. Protein integrity of antigen load in microparticles was maintained. |
[144] |
| Poly(glycerol adipate-co-ωpentadecalactone) (PGA-co-PDL) | 322.83 ± 4.25 nm (with the adsorption of PspA4Pro) | n/a | PspA4Pro (PspA clade 4) |
Antigen PspA4Pro release from PGA-co-PDL nanoparticle was confirmed. PspA4Pro antigenicity was retained and the functional epitopes of the antigen were active in the formulation. |
[145] |
| Nanocomposite microparticles (NP/NCMP) | ~2 μm | EF3030 (serotype 19F, PspA1) ATCC6303 (serotype 3, PspA5) |
PspA4Pro (PspA clade 4, encompassing mature N-terminal region till proline-rich region) | Anti-PspA4Pro IgG antibodies in serum and lungs were induced. Binding analysis of serum IgG to intact bacteria revealed efficient binding to bacteria expressing PspA from clades 3, 4, and 5 (family 2). However, no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Immunization with NP/NCMP PspA4Pro was unable to decrease the bacterial load in the lungs following challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Local and systemic antibodies were induced and offered protection against only one strain expressing PspA in homologous family 2. |
[146] |
| Bacterium-like particles (BLP) | Similar to the size of the bacterium—0.5 to 5μm | ATCC6303 (PspA family 2 clade 5, serotype 3) ATCC101813 (PspA family 1 clade 2, serotype 3) |
PspA, family2 clade-4 (derived from N-terminal α-helical region and the proline-rich region of pneumococcal strain EF5668 | Safe and affordable. Both PspA-specific IgG and PspA-specific IgA were induced. Complete protection in a mouse challenge model (immunized with BLPs/PspA-PA) with pneumococci from two different clades of both homologous and heterologous PspA families that led to high protection against challenges with heterologous pneumococci and showed broader specificity. |
[147] |
| ATCC6304 (PspA family 1, clade 1) ATCC10813 (PspA family 1, clade 2) ATCC6319 (PspA family 2, clade 3) ATCC6314 (PspA family 2, clade 4) ATCC6303 (PspA family 2, clade 5) |
PspA2 and PspA4 | High levels of serum IgG and mucosal SIgA were induced. Binding to pneumococcal strains expressing PspA from clades 1 to 5 was observed. Immunization with the PspA-BLP vaccine conferred protection against fatal intranasal challenge with both PspA family 1 and family 2 pneumococcal strains. |
[149] | ||
| Chitosan-DNA Nanoparticles | The average size of particle was 392 nm; zeta potential was +12.5 mV | S. pneumoniae ATCC 6303 (serotype 3) | pVAX1-PsaA (867-bp PsaA gene was amplified from S. pneumoniae genomic DNA ATCC 6303; serotype 3) |
Anti-PsaA IgG antibody in serum and anti-IgA antibody in mucosal lavages were increased. Cellular immune responses were induced. Fewer pneumococci were recovered from the nasopharynx of mice immunized with chitosan-PsaA. Mucosal and systemic immune responses were generated and ultimately prevented pneumococcal nasopharyngeal colonization. |
[153] |
| Chitosan-PsaA protein | The average size of particle was 691 nm; zeta potential was +21.1 mV | S. pneumoniae ATCC 6303 (serotype 3) | PsaA | The systemic (IgG in serum) and mucosal (IgA in mucosal lavage) specific antibodies were enhanced. Protection against acute otitis media following middle ear challenge with pneumococcus serotype 14 was increased The survival rate of mice immunized with chitosan–PsaA nanoparticles in an intraperitoneal challenge with pneumococcus serotype 3 or serotype 14 was improved. |
[154] |
| Chitosan-PCV13 | The particle size of 46.1nm | PCV13; Prevnar®; Pfizer Inc | No difference was observed in the level of total antibodies against Pn14PS antigen in the mouse groups with or without adjuvant codelivery. Both chitosan-PCV codelivery and Quil-A adjuvant (control) elicited IgG1, IgG2a, IgG2b, and IgG3 antibodies. |
[155] | |
| Cationic liposomes (DOTAP and DC-chol) | The particle size of 137.9 ± 11.6 nm; Zeta potential of 4.0 ± 2.1 mV | n/a | PspA, family 1 clade-2 | Liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and cholesteryl 3β-N- (dimethylaminoethyl)carbamate (DC-chol) (DOTAP/DC-chol liposome). Provideed protective immunity against lethal inhalation of S. pneumoniae, and improved the survival rate of infected mice. Intranasal immunization with DOTAP/DC-chol liposomes carrying PspA induced both mucosal and systemic response. PspA-specific Th17 response was elicited. It plays a pivotal role in controlling S. pneumoniae infection by host innate immune response. |
[156] |
| Gold nanoparticles (GNPs) | Mean gold core of 1.8 ± 0.5 nm; Average molecular weight of 84 to 97 kDa. | n/a | S. pneumoniae type 14, polysaccharide (Pn14PS) conjugated to CRM197 (Pn14PSCRM197), and T-helper ovalbumin 323–339 peptide (OVA323–339) | Specific anti-Pn14PS IgG antibodies were triggered. T-helper cell activation was promoted by glyconanoparticles The functionality of the antibodies was maintained as the antisaccharide antibodies promoted the phagocytosis of type 14 bacteria by human leukocytes. |
[157] |
| Gold-glyco- nanoparticles | Mean gold core of 1.2 ± 0.3 nm; Average molecular weight of 45 to 55 kDa. | n/a | Serotype 14 (Tetra-14) and serotype 19F (Tri-19F), and a T-helper ovalbumin 323–339 peptide (OVAp) | A synthetic carbohydrate vaccine. GNPs functionalized with Pn19F and/or Pn14 saccharide ligands. The titers of specific IgG antibodies towards type 14 polysaccharide were enhanced. |
[158] |
| PspA-based polyanhydride | The particle size of 50:50 CPTEG: CPH 455 ± 175; Zeta potential of −33.1 ± 5.1 mV |
S. pneumoniae strain A66.1(PspA family 1, clade 2) |
Pneumococcal surface protein A (PspA) | A room temperature stable PspA-based polyanhydride nanovaccine reduced the cost of vaccine care and transportation. Single immunization of the mice with nanovaccine and upon challenge presented significantly higher survival rates compared to mice immunized with soluble protein alone. A 25-fold reduction in protein dose of nanovaccine presented higher survival rates in immunized mice compared to the PspA soluble protein. A single dose of PspA-based nanovaccine against S. pneumoniae induced protective immunity. |
[161] |
| Lipoprotein | n/a | S. pneumoniae D39 | MetQ, PnrA, PspA and DacB proteins | High antibody titers were present in sera from mice immunized with the lipoproteins MetQ, PnrA, PsaA, and DacB.Mice were immunized intranasally with PnrA, DacB, and MetQ using cholera toxin subunit B (CTB) as an adjuvant, followed by an intranasal challenge with S. pneumoniae D39. No pneumococcal colonization was observed in vaccination using PnrA while DacB and MetQ led to reduction of the bacterial load. The increased production of antigen-specific IL-17A in the nasal cavity reduced bacteria colonization. High systemic IgG levels were induced with a predominance for the IgG1 isotype, except for DacB. |
[162] |
| ~ 40 nm | S. pneumoniae Rx1 | PspA, family 1, clades 2 | cCHP nanogel contained 20 amino groups per 100 glucose units. Longer retention of PspA (in nanogel) was observed in the nasal cavity when compared with the administration of PspA alone. No deposition of [18F]-PspA was seen in the olfactory bulbs or brain. PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis) were induced. |
[163] |
Note: n/a: not available; PspA: pneumococcal surface protein A; MetQ: methionine binding protein; PnrA: pneumococcal nucleoside-binding protein; DacB: L,D-carboxypeptidase; PsaA: pneumococcal surface adhesin A; cCHP: cationic cholesteryl group-bearing pullulan.