Table 3.
Particulate vaccines (nanoparticle, viral and quasi-viral, microparticle, bacterial or yeast) Toxoplasma
| Antigen | Toxoplasma strain | Particle type | Route of injection and the location and dose | Booster |
|---|---|---|---|---|
| rSAG1, rSAG2 and rGRA1 | N/A | Muramyl dipeptide (MDP) microparticle |
Intramuscularly in the dorsal neck region 300 µg Ag in 1 ml PBS |
Boosted once, 6 weeks after the initial one |
| Microneme protein 16 (TgMIC16) |
Challenged by virulent T. gondii RH strain tachyzoites |
Yeast S. cerevisiae EBY100 strain (containing pCTCON2 plasmid) |
Intraperitoneally with heat-killed transfected yeast or orally with live transfected yeast 100 µl (4 × 107 cells) |
Boosted twice at weeks 2 and 4 after the initial one |
| ROP2 | Protein sequence from T. gondii RH strain challenge by T. gondii RH strain |
M. bovis BCG, sub-strain Pasteur pMV262 vector |
Subcutaneous 0.1 ml (107 cfu/ml) BCG/ pMV262-ROP2 |
Boosted once after 4 weeks by the same dose |
| ROP18 | N/A | Poly (lactideco-glycolide) (PLGA) nanoparticle | Intraperitoneally (ip) with 10 μg rROP18 | Bossted twice in 2-week intervals |
| Microneme protein 8 (MIC8) | Challenge by highly virulent T. gondii (RH) (oral challenge) | Virus-like particles (derived from baculovirus + influenza matrix protein 1 {M1}) |
Intranasal immunization (IN), intramuscular immunization (IM) with 75 μg of total MIC8 VLP protein per mouse |
Boosted once 4 weeks later |
| MIC3, ROP9, and SAG2 | Challenge by lethal T. gondii RH strain | Recombinant adenoviruses | 50 µL purified recombinant adenoviruses (109 PFU) intramuscular injection at 2-week intervals | Boosted once, 2 weeks later |
| rSAG1 | Tachyzoites of T. gondii RH strain for challenge | PLGA |
Subcutaneously (s.c) immunized in the right-hind footpad 20 μg of rSAG1-adsorbed PLGA nanoparticles and rSAG1-encapsulated PLGA nanoparticle |
Once, 3 weeks later by the same dose |
| Rhoptry protein 18 (ROP18) and microneme protein 8 (MIC8) | Intraperitoneally (IP) with tachyzoites of GT1 strain or orally challenged with T. gondii ME49 strain | Virus-like particle |
Intranasally (IN) with 60 mg of ROP 18VLPs or MIC8 VLPs or a mixture of 30 mg ROP18 VLPs and 30 mg MIC8 VLPs (combination VLP vaccine) |
Once, 4 weeks later by the same protocol |
| SAG1 | N/A | Polymeric nanospheres | Intraperitoneal (i.p.) injections 10 mg rSAG1 protein + montanide or rSAG1 + PLGA intranasally | Boosted twice with 2-week intervals |
| SAG1 | Challenged by T. gondii RH | Virus-like particle |
Intramuscular administration with SAG1-VLPs (120 µg) |
Boosted once after 4 weeks |
| Apical membrane antigen 1 (AMA1) | Challenged with T. gondii ME49 | Virus-like particle | Intranasally immunized with 100 μg of VLPs | Boosted once after a 4-week interval |
| Adjuvants | Immune response elicited by vaccine | Animal used for vaccine response evaluation | Year of publication | |
|---|---|---|---|---|
| rSAG1, rSAG2 and rGRA1 were covalently conjugated to 1 µm MDP microparticles (10 mg MDPmicroparticle/1 mg recombinant protein) |
Increased IFN-g in the rGRA1 Immunization with recombinant proteins rSAG1, rSAG2 and rGRA1 alone or as a cocktail vaccine elicited IgG2 and a weak IgG1 response |
Sheep | 2017 | |
| The yeast itself as an adjuvant |
In both intraperitoneally orally vaccinated groups: Higher serum Ab concentration (dominant IgG2a over IgG1) Higher lymphocyte proliferative response Higher percentage of CD4 + and CD8 + T cells increased levels of IL-2 and IFN-g (but not IL-4 or IL-10) increased survival time |
BALB/c mice | 2018 | |
| The BCG itself as an adjuvant |
Increased survival time Elevated total Ab (humoral immunity) Increased IFN-g and IL-2 production Higher percentage of CD4 + cells (cellular immunity) |
BALB/c mice | 2007 | |
| Montanide adjuvant or PLGA nanoparticle |
Both adjuvant group and PLGA demonstrated elevated IgG IgA levels was significantly higher in PLGA + ROP18 group In the PLGA group the IgG2a was dominant while in the adjuvant group the IgG1 was dominant |
Swiss-Webster mice | 2017 | |
| None |
IN mice group showed higher levels of T. gondii-specific IgG antibody response compared to IM mice group IN group (IgG1 predominance {Th2}) IN induced higher levels of systemic and mucosal antibody responses IM group no effective Ab response Higher CD4 T cell, CD8 T cell and germinal center B cells in both IN and IM groups Following parasite challenge higher levels of IFN-γ and IL-6 were detected in Naïve and IM groups compared to IN group (IN group reduced inflammatory reaction but higher humoral) 100% survival of IN group and 60% survival of IM group, 100% mortality in the control group |
BLAB/c mice | 2017 | |
| None, the adenovirus particle itself can have adjuvant effects |
In the mice immunized with the recombinant adenoviruses group: extremely significantly higher T. gondii-specific IgG antibody Levels Increased production of IL-6, TNF-a, IL-22, IFN-g, IL-17A and IL-10 Increased T lymphocytes (and activated Th lymphocytes) percentage in the spleen Elevated survival time |
BALB/c mice | 2019 | |
| Adsorption or encapsulation of rSAG1 to PLGA nanoparticles can provide some adjuvant effects |
Increased survival time in rSAG1 loaded PLGA groups Total serum IgG and high IgG2a/IgG1 ratio in rSAG1 loaded PLGA groups higher amounts of IFN-γ (but unchanged IL-10) in rSAG1 loaded PLGA groups after in vitro Ag re-stimulation of spleen cells |
BALB/c mice | 2020 | |
| None |
All three vaccine groups showed similar levels of IgG antibody responses which were significantly increased after boost immunization (combined ROP18 VLPs + MIC8 VLPs vaccine immunization showed a higher level of IgA antibody responses) higher levels of CD4 + T cells, CD8 + T cells, and memory phenotypic T cells (combination T. gondii VLP immunization induces higher T cell responses after challenge) Combination T. gondii ROP18 and MIC8 VLP immunization attenuates apoptotic cellular response after challenge Combination VLP vaccine immune sera exhibit higher activity of controlling parasite loads in vivo Combination VLP vaccination reduces pro-inflammatory cytokine (IFN-g and IL-6) responses after challenge Combined VLP vaccines improved protection against challenge infection with T. gondii via an oral or IP route |
BALB/c mice | 2018 | |
| Montanide adjuvant or PLGA nanoparticle |
Both adjuvant group and PLGA demonstrated elevated IgG IgA levels was significantly higher in PLGA + ROP18 group In the PLGA group the IgG2a was dominant while in the adjuvant group the IgG1 was dominant |
Swiss-Webster mice | 2018 | |
| None |
SAG1-VLP immunization: Significant increase of the antibody (IgG, IgG1, IgG2a, and IgA) levels (IgG1 predominance) not only decreases the production of cytokines (IL-4, IL-12, and IFN-g) associated with the infection of pathogens in the host, but also effectively inhibits the inflammatory cytokines (IL-1 , IL-6, and TNF-a) after T. gondii infection The survival rates of the immunized infection group were significantly increased compared to the non-immunized infection group |
Balb/c mice | 2020 | |
| None |
In the AMA1 VLPs-immunized group: higher levels of T. gondii-specific IgG and IgA higher germinal center B cell populations smaller cysts and lower cyst counts were detected from the brain, reduced body weight loss, higher survival rate |
BALB/c mice | 2020 |