Table 2. Baseline characteristics of included studies based on immunization experiments with DNA or protein vaccines against Toxoplasma gondii in mouse models.
| Antigen | Adjuvant or carrier | Ag delivery | Mouse strain | Challenge | Immune responses | Brain cyst load | Survival | Reference |
|---|---|---|---|---|---|---|---|---|
| CDPK1 | IL-15 and IL-21 | Plasmid, i.m. | Kunming | Acute: 1×103 tachyzoites, RH strain, i.p. | Induced a strong IgG antibody response (p<0.05) | Reduced | Increased survival time | [56] |
| Chronic: 20 cysts of the PRU strain, orally | The levels of IgG antibody in the pVAX-CDPK1+pVAX/IL-21/IL-15 group was significantly higher than that with pVAX-CDPK1 alone (p<0.05) | pVAX-CDPK1: 45.7% (p<0.05) | pVAX-CDPK1: 17.3± 4.3 days (p<0.05) | |||||
| Mixed IgG1/IgG2a response with the predominance of IgG2a over IgG1 | pVAX-CDPK1+pVAX/IL-21/IL-15: 72.7% (p<0.05) | pVAX-CDPK1+pVAX/IL-21/IL-15: 19.2± 5.1 days (p<0.05) | ||||||
| Higher levels of IgG2a and IgG1 in mice immunized with pVAX-CDPK1+pVAX/IL-21/IL-15 compared with pVAX-CDPK1 group (p<0.05) | All control mice died within 6 days | |||||||
| ↑ Splenocyte proliferation significantly in the groups immunized with pVAX-CDPK1 or pVAX-CDPK1+pVAX/IL-21/IL-15 (especially in the latter group) | ||||||||
| ↑ IFN-γ, IL-2, IL-4, and IL-10 (especially in the pVAX-CDPK1+pVAX/IL-21/IL-15 group, p<0.05) | ||||||||
| ↑ Percentages of CD4+ T and CD8+ cells (p<0.05) | ||||||||
| IL-7 and IL-15 | Plasmid, i.m. | Kunming | Acute: 1×103 tachyzoites, RH strain, i.p. | Induced a strong IgG antibody response (p<0.05) | Reduced | Increased survival time | [54] | |
| Chronic: 10 cysts of the PRU strain, orally | The levels of IgG antibody in the pVAX-CDPK1+pVAX/IL-7/IL-15 group was significantly higher than that with pVAX-CDPK1 alone (p<0.05) | pVAX-CDPK1: 46% (p<0.05) | pVAX-CDPK1: 14.13±3.85 days (p<0.05) | |||||
| Mixed IgG1/IgG2a response with the predominance of IgG2a over IgG1 | pVAX-CDPK1+pVAX/IL-7/IL-15: 73.5% (p<0.05) | pVAX-CDPK1+pVAX/IL-7/IL-15: 18.07± 5.43 days (p<0.05) | ||||||
| Higher levels of IgG2a and IgG1 in mice immunized with pVAX-CDPK1+pVAX/IL-7/IL-15 compared with pVAX-CDPK1 group (p<0.05) | All control mice died within 9 days | |||||||
| ↑ Splenocyte proliferation significantly in the groups immunized with pVAX-CDPK1 or pVAX-CDPK1+pVAX/IL-7/IL-15 (especially in the latter group) | ||||||||
| ↑ IFN-γ, IL-2, IL-4, and IL-10 (especially in the pVAX-CDPK1+pVAX/IL-7/IL-15 group, p<0.05) | ||||||||
| ↑ Percentages of CD4+ T and CD8+ cells (p<0.05) | ||||||||
| CDPK2 | - | Plasmid, i.m. | BALB/c | 1×103 tachyzoites, RH strain, i.p. | Induced a strong IgG antibody response (p<0.05) | NR | Increased survival time (14±2.32 days, p<0.05) | [58] |
| Mixed IgG1/IgG2a response with the predominance of IgG2a over IgG1 | All control mice died within 8 days | |||||||
| ↑ Proliferation SI (1.76±0.24, p<0.05) | ||||||||
| ↑ Percentages of CD4+ T and CD8+ cells (p<0.05) | ||||||||
| ↑ IFN-γ (694.56±76.72 pg/mL, p<0.05), IL-12 p-70 (334.51±7.52 pg/mL, p<0.05), and IL-10 (421±23.25 pg/mL, p<0.05) | ||||||||
| Similar levels of IL-4 between the different immunized and unimmunized groups (p>0.05) | ||||||||
| CDPK3 | - | Plasmid, i.m. | Kunming | Acute: 1×103 tachyzoites, RH strain, i.p. | Induced a strong IgG antibody response (p<0.05) | Reduced (p<0.05) | Increased survival time (13.5±4.89 days, p<0.05) | [52] |
| Chronic: 10 cysts of the PRU strain, orally | ↑ Proliferation SI (1.30±0.18, p<0.05) | |||||||
| Mixed IgG1/IgG2a response with the predominance of IgG2a over IgG1 (p<0.05) | ||||||||
| ↑ Percentages of CD4+ T cells (p<0.05) | ||||||||
| ↑ IFN-γ (612.11±128.56 pg/mL, p<0.05), IL-2 (263.79±35.43 pg/mL, p<0.05), IL-12 p-70 (129.63±77.42 pg/mL, p<0.05), IL-4 (32.42±2.74 pg/mL, p<0.05), IL-10 (870.12± 226.50 pg/mL, p<0.05), and IL-23 (87.59±7.14 pg/mL, p<0.05) | ||||||||
| CDPK5 | - | Plasmid, i.m. | Kunming | Acute: 1×103 tachyzoites, RH strain, i.p. | Induced a strong IgG antibody response (p<0.05) | Reduced (39.13%, p=0.005) | Prolonged survival time, but the difference was not statistically significant (8.67±4.34 days, p>0.05) | [55] |
| Chronic: 10 cysts of the PRU strain, orally | ↑ Proliferation SI (1.92±0.07, p<0.001) | |||||||
| Mixed IgG1/IgG2a response with the predominance of IgG2a over IgG1 | ||||||||
| ↑ Percentages of CD4+ T and CD8+ cells (p=0.04) | ||||||||
| ↑ IFN-γ (982.68±378.22 pg/mL, p<0.05), IL-2 (266.04±9.13 pg/mL, p<0.05), IL-12 p-70 (96.84±4.06 pg/mL, p<0.05), and IL-10 (136.53±71.63 pg/mL, p<0.05) | ||||||||
| Similar levels of IL-4 between the different immunized and unimmunized groups (p>0.05) | ||||||||
| CDPK6+ROP18 | Montanide™ ISA 206 VG (206) and PLG | Proteins (10 µg of each), s.c. | Kunming | Acute: 1×103 tachyzoites, RH strain (type I), i.p. | ↑ Specific IgG antibody responses in the mice immunized with rROP18+PLG or rCDPK6+rROP18+PLG | Reduced (varied from 47.7% to 73.6%, p<0.001) | Increased survival time | [53] |
| Main groups: PBS rROP18 rROP18+rCDPK6 rROP18+206 rROP18+rCDPK6+206 rROP18+PLG rROP18+rCDPK6+PLG |
Chronic: 10 cysts of the PRU strain (type II), orally | ↑ Splenocyte proliferation significantly (highest in mice immunized with rCDPK6+rROP18+PLG, p<0.001), compared with the control groups | The average survival time of the mice immunized with the various protein vaccines (8.56 days) was slightly longer than that in the controls (8 days) | |||||
| ↑ CD4+ and CD8+ T cells in mice immunized with the various protein vaccines | rROP18+PLG (10.9±2.58 days, compared with the controls, p<0.05) | |||||||
| ↑ Levels of CD4+ (p<0.001) and CD8+ T lymphocytes (p<0.01) in mice immunized with protein–PLG microparticles, compared with controls | rROP18 (10.1±1.52 days, compared with the controls, p<0.05) | |||||||
| ↑ Percentages of CD4+ cells in mice immunized with rROP18+206 and rROP18+PLG, compared with controls (p<0.05) | ||||||||
| ↑ IFN-γ and IL-2 significantly in the mice immunized with various proteins, compared with the control groups (p<0.05) | ||||||||
| ↓ IL-4 and IL-10, compared with the control groups (p<0.05) | ||||||||
| Similar levels of IL-12 between vaccinated and control groups (p>0.05). | ||||||||
| Induced Th1-biased immune responses |
CDPK, calcium-dependent protein kinase; IL, interleukin; i.m., intramuscular; i.p, intraperitoneally; ↑, increase; ↓, decrease; IFN-γ, interferon-γ; SI, stimulation index; NR, not reported; PBS, phosphate-buffered saline; ROP, rhoptry antigen; PLG, polylactide-co-glycolide.