Table 1.
Recent Chagas Disease Vaccine Platforms and Formulations.
|
Antigens and Use |
Adjuvants and Delivery Systems | Immune Response | Efficacy Against Parasite | Efficacy Against Cardiac Damage and Dysfunction | References | |
|---|---|---|---|---|---|---|
| Therapeutic vaccines | ||||||
| DNA | TcG2+TcG4, therapeutic during acute phase |
Plasmids or nano plasmids | CD4+ and CD8+ producing IFNg, PRF, and GRZ | Decreased parasite burden in cardiac and skeletal muscle | Decrease in fibrosis in heart and skeletal muscle, decrease in oxidative stress | [40,41] |
| DNA | Cruzipain and Chagasin plasmids with Salmonella carrier, therapeutic during acute phase |
GM-CSF expression plasmid | Increased IFNγ and antibodies | Decreased parasite burden in blood and heart, and increased survival | Decreased cardiac inflammation | [42] |
| Peptides | 10 peptide epitopes mixture, therapeutic during acute phase | TLR4 agonist (MPLA) | Increased IFNγ | Decreased cardiac parasite burden, increased survival |
N/A | [43] |
| Recombinant proteins | Tc24, TSA-1 and their optimized variants, therapeutic during acute phase | TLR4 agonists (E6020, MPLA, GLA), TLR9 agonist (CpG), nanoparticles | Antibodies, IFNγ, and CD4+ and CD8+ activation | Decreased cardiac parasite burden, increased survival |
Decrease in cardiac inflammation and fibrosis | [44,45,46,47] |
| Recombinant proteins | Tc24, therapeutic during chronic phase | TLR4 agonists (E6020) | High IFNγ and low IL4, and antibodies | Decreased parasitemia | Decrease in cardiac inflammation and fibrosis | [48] |
| Recombinant proteins | Tc24-C4, therapeutic combined with low dose Benznidazole | TLR4 agonist (E6020) | Increased IFNγ, IL12, TNFa, IL2, IL4 and IL10, and CD4+ and CD8+ T cell activation | Decreased parasitemia, increased survival | N/A | [49] |
| Viral vectors | Recombinant Adenovirus expression ASP2, therapeutic during acute phase | TNFa, iNOS, TLR4, and IL-10 expression in the liver | Increased survival, decreased parasite burden in liver | N/A | [50] | |
| Viral vectors | Recombinant adenovirus expressing ASP2 and TS, therapeutic during chronic phase | IFNγ and CD8+ T cells | Increased survival | Decreased cardiac fibrosis and dysfunction | [51] | |
| Preventative vaccines | ||||||
| Live parasites | Drug-cured primary infection, preventative | N/A | N/A | Sustained decrease in parasite burden in all body | N/A | [52] |
| Live parasites | Live attenuated parasite (inducible expression of alpha-toxin, and cecropin A), preventative | N/A | IFNγ, TNFa, CD4+ and CD8+ T cell activation, antibodies, and NK cells | No detectable parasites | Decrease in cardiac inflammation | [53,54] |
| Live parasites | Live attenuated parasite (TCC attenuated strain), preventative short term | IFNγ expressing plasmid | Antibodies and mixed Th1/Th2 response | Decreased parasitemia and increased survival | N/A | [55] |
| DNA | TcG2+TcG4, preventative short term | Plasmids alone or with Trypanosoma rangeli and/or Quil A as adjuvants | Antibodies, CD4+ and CD8+ producing IFNγ, TNFa, and PRF | Decreased parasite burden in cardiac and skeletal muscle | [56] | |
| DNA | Cruzipain plasmid, preventative short term |
GM-CSF plasmid | Antibodies and DTH | Decreased parasitemia, increased survival | Decreased cardiac tissue damage | [57] |
| DNA | Cruzipain, Tc52, Tc24 plasmids, preventative short term |
Salmonella enterica carrier | Trypanolytic antibodies, DTH, IFNγ, IL12, and IL10 | Decreased parasitemia, increased survival | Decreased cardiac tissue inflammation, necrosis | [58] |
| Recombinant proteins | Cruzipain fused with staphylococcal superantigen, preventative short term | TLR9 agonist (CpG) | Neutralizing antibodies and DTH | Decreased parasitemia and increased survival | N/A | [59] |
| Recombinant proteins | Recombinant Traspain, Cruzipain and ASP-2 fusion protein, preventative short term | c-di-AMP adjuvant (STING agonist) | Neutralizing antibodies, CD4+ and CD8+ T cell activation, IFNγ, TNFa, IL2, and IL17 | Decreased parasitemia and increased survival | Decreased cardiac damage (CK, CK-MB), decreased necrosis and inflammation in the heart and skeletal muscle | [60] |
| Recombinant proteins | Recombinant Tc52 fragment, preventative short term | c-di-AMP adjuvant (STING agonist) | Antibodies, CD4+ and CD8+ T cell activation, IFNγ, and IL17 | Decreased parasitemia and increased survival | N/A | [61] |
| Recombinant proteins | TcTASV, preventative short term | Unlipidated Outer Membrane Protein 19 of Brucella abortus (U-Omp19) as adjuvant |
Trypanolytic antibodies, IFNγ, and IL17 | Decreased parasitemia and increased survival | N/A | [59] |
| Recombinant proteins | Enolase, preventative short term | Freund complete/incomplete adjuvant | Antibodies, IFNγ, and IL2 | Decreased parasitemia and increased survival | Decreased cardiac and skeletal muscle inflammation | [62] |
| Recombinant proteins | Trans-Sialidase fragment, Preventative short term | ISPA lipidic cages, ISCOMATRIX, or Freund adjuvant | Trypanolytic antibodies, IFNγ, CD4+ and CD8+ T cell activation, Treg activation | Decreased cardiac parasite burden, increased survival |
Decreased cardiac inflammation | [63,64] |
| Glycotope | αGal glycotope, preventative short term | TLR4 agonist (Liposomal-monophosphoryl lipid A) | Trypanolytic antibodies, CD4+ and CD8+ T cell activation | Decreased parasite burden in multiple tissues, increased survival | Decreased cardiac inflammation and necrosis | [39] |
| Viral vectors | Recombinant Adenovirus and modified Vaccinia Ankara virus expressing ASP-2 and Trans-sialidase, preventative vaccination | PBS | Decreased parasite burden during the acute phase in all body, but no impact on long-term burden during chronic phase | N/A | [52] | |
| Bacterial vectors | Recombinant Mycobacterium bovis (BCG) expressing trans-sialidase and cruzipain fragments, preventative short term | Trypanolytic antibodies, and DTH, CD4+ expressing IFNγ, IL17, IL10, and CD8+ | Increased survival | Decreased cardiac inflammation and fibrosis | [65] | |
| Heterologous prime-boost combination | Salmonella enterica expressing Traspain and ASP-2 | TLR9 agonist (CpG) | Increased IFNγ, IL17, low IL4, CD4+, and CD8+ T cell activation | Decreased parasite burden in blood, heart and skeletal muscle, and increased survival | Decreased inflammation and improved EKG | [66] |
| Heterologous prime-boost combination | Recombinant 80 kDa prolyl oligopeptidase (Tc80) and plasmid DNA |
TLR9 agonist (CpG) | Increased IFNγ, IL2, TNFa, CD4+, and CD8+ T cell activation | Decreased parasitemia, and increased survival | Decreased cardiac inflammation, damage (CK and CK-MB), improved EKG | [67] |
| Heterologous prime-boost combination | Recombinant Tc52 and plasmid DNA with Salmonella carrier, preventative short term | TLR9 agonist (CpG) | Trypanoplytic antibodies, Increased IFNγ, IL10, CD4+, and CD8+ T cell activation | Decreased parasitemia, and increased survival | Decreased cardiac inflammation | [68] |
| Heterologous prime-boost combination | TcG1, TcG2, and TcG4 expression plasmids and recombinant proteins, preventative long term | IL2 and GM-CSF plasmids | Increased IFNγ, TNFa, CD4+ and CD8+ T cell activation | N/A | N/A | [69] |
PRF—perforin; GZN—granzyme; DTH—delated type hypersensitivity; TLR—Toll-like receptor; IL—interleukin; IFN—interferon; TNF—tumor necrosis factor; EKG—electrocardiogram; N/A—not applicable.