Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Production of Recombinant ChimeraT Protein
2.2. Preparation of Liposomes Incorporating ChimeraT
2.3. Mice and Parasites
2.4. Vaccination of BALB/c Mice and Infection with L. infantum
2.5. Evaluating Cellular Responses before and after L. infantum Infection
2.6. Humoral Response Generated before and after L. infantum Challenge
2.7. Evaluation of the Parasite Load by the Limiting Dilution Technique and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)
2.8. Human Sera
2.9. Post-Therapy Serological Follow-up
2.10. Statistical Analysis
3. Results
3.1. Cellular Responses in Vaccinated Mice before and after L. infantum Infection
3.2. Total IgG, IgG1, and IgG2a Antibody Responses in Vaccinated Mice before and after L. infantum Infection
3.3. Estimation of Parasite Burden
3.4. Post-Therapy Serological Follow-up
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Immunization | Ratio IFN-γ/IL-10 in Spleen Cells Stimulated with | |||||
---|---|---|---|---|---|---|
Before Infection | After Infection | |||||
Medium | ChimeraT | SLA | Medium | ChimeraT | SLA | |
Saline | 0.8 | 1.0 | 0.96 | 0.95 | 1.38 | 0.13 |
Saponin | 1.03 | 1.23 | 1.15 | 1.04 | 1.80 | 0.20 |
Empty Liposome | 1.03 | 1.29 | 1.01 | 1.10 | 1.43 | 0.21 |
ChimeraT/Saline | 1.18 | 4.28 * | 2.31 | 1.05 | 8.47 * | 0.79 |
ChimeraT/Saponin | 1.42 | 19.96 * | 12.21 * | 1.42 | 30.12 * | 17.31 * |
ChimeraT/Liposome | 1.41 | 20.70 * | 12.03 * | 1.37 | 32.78 * | 19.33 * |
Immunization | (A) Before Infection | (B) After Infection | ||||||
---|---|---|---|---|---|---|---|---|
Anti-ChimeraT | Anti-SLA | Anti-ChimeraT | Anti-SLA | |||||
IgG2a/ IgG1 | IgG1/ IgG2a | IgG2a/ IgG1 | IgG1/ IgG2a | IgG2a/ IgG1 | IgG1/ IgG2a | IgG2a/ IgG1 | IgG1/ IgG2a | |
Saline | 1.12 | 0.89 | 0.79 | 1.27 | 0.92 | 1.09 | 0.10 | 10.10 |
Saponin | 1.25 | 0.80 | 0.63 | 1.59 | 0.82 | 1.22 | 0.18 | 5.60 |
Empty Liposome | 1.15 | 0.89 | 0.78 | 1.28 | 0.83 | 1.20 | 0.26 | 3.85 |
ChimeraT/Saline | 1.42 | 0.7 | 1.26 | 0.79 | 0.95 | 1.05 | 0.45 | 2.22 |
ChimeraT/Saponin | 8.84 * | 0.11 | 3.14 * | 0.32 | 6.81 * | 0.15 | 4.19 * | 0.24 |
ChimeraT/Liposome | 8.58 * | 0.12 | 3.02 * | 0.33 | 10.27 * | 0.10 | 5.29 * | 0.19 |
(A) Before VL Treatment | (B) After VL Treatment | |||
---|---|---|---|---|
Antigen | IgG2/IgG1 | IgG1/IgG2 | IgG2/IgG1 | IgG1/IgG2 |
ChimeraT | 1.08 | 0.93 | 2.99 | 0.33 |
SLA | 0.17 | 5.75 | 0.47 | 2.13 |
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Lage, D.P.; Ribeiro, P.A.F.; Dias, D.S.; Mendonça, D.V.C.; Ramos, F.F.; Carvalho, L.M.; Steiner, B.T.; Tavares, G.S.V.; Martins, V.T.; Machado, A.S.; et al. Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis. Vaccines 2020, 8, 289. https://doi.org/10.3390/vaccines8020289
Lage DP, Ribeiro PAF, Dias DS, Mendonça DVC, Ramos FF, Carvalho LM, Steiner BT, Tavares GSV, Martins VT, Machado AS, et al. Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis. Vaccines. 2020; 8(2):289. https://doi.org/10.3390/vaccines8020289
Chicago/Turabian StyleLage, Daniela P., Patrícia A.F. Ribeiro, Daniel S. Dias, Débora V.C. Mendonça, Fernanda F. Ramos, Lívia M. Carvalho, Bethina T. Steiner, Grasiele S.V. Tavares, Vívian T. Martins, Amanda S. Machado, and et al. 2020. "Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis" Vaccines 8, no. 2: 289. https://doi.org/10.3390/vaccines8020289