CoChat
Sign Up
Cited by 77Toxoplasma gondii Research StudiesCoccidia and coccidiosis researchParasitic Infections and Diagnostics

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Toxoplasmosis vaccines: what we have and where to go?

Open access
Zhang, Yizhuo, Li, Dan, Lu, Shaohong, Zheng, Bin·2022·npj Vaccines
DOI 10.1038/s41541-022-00563-0PMC PMC9618413
Open this paper in CoChat — free accountOpen PDF

Abstract

Despite recent major advances in developing effective vaccines against toxoplasmosis, finding new protective vaccination strategies remains a challenging and elusive goal as it is critical to prevent the disease. Over the past few years, various experimental approaches have shown that developing an effective vaccine against T. gondii is achievable. However, more remains unknown due to its complicated life cycle, difficulties in clinical translation, and lack of a standardized platform. This minireview summarizes the recent advances in the development of T. gondii vaccines and the main obstacles to developing a safe, effective and durable T. gondii vaccine. The successes and failures in developing and testing vaccine candidates for the T. gondii vaccine are also discussed, which may facilitate the future development of T. gondii vaccines.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41541-022-00563-0

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Anti-T. gondii vaccines.
Fig. 1 Anti-T. gondii vaccines.CC BY · PubMed Central
Fig. 2 Challenges in T. gondii vaccine development.
Fig. 2 Challenges in T. gondii vaccine development.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 2 references

Research works printed but not linked: 88

  1. Dunay, I. R., Gajurel, K., Dhakal, R., Liesenfeld, O. & Montoya, J. G. Treatment of toxoplasmosis: historical perspective, animal models, and current clinical practice. Clin. Microbiol. Rev. https://doi.org/10.1128/cmr.00057-17 (2018). · DOI
  2. Rémy, V., Zöllner, Y. & Heckmann, U. Vaccination: the cornerstone of an efficient healthcare system. J. Mark. Access. Health Policy https://doi.org/10.3402/jmahp.v3.27041 (2015). · DOI
  3. Costa-Silva, T. A., Borges, M. M., Galhardo, C. S. & Pereira-Chioccola, V. L. Immunization with excreted/secreted proteins in AS/n mice activating cellular and humoral response against Toxoplasma gondii infection. Acta Trop. 124, 203–209 (2012). · DOI
  4. Wang, Y., Zhang, D., Wang, G., Yin, H. & Wang, M. Immunization with excreted-secreted antigens reduces tissue cyst formation in pigs. Parasitol. Res. 112, 3835–3842 (2013). · DOI
  5. Meshkini, E., Aminpour, A., Hazrati Tappeh, K., Seyyedi, S. & Shokri, M. Evaluation of adjuvant effectiveness of alum-propranolol mixture on the immunogenicity of excreted/secreted antigens of Toxoplasma gondii RH strain. Adv. Pharm. Bull. 11, 570–577 (2021). · DOI
  6. Dubey, J. P. Toxoplasmosis in sheep-the last 20 years. Vet. Parasitol. 163, 1–14 (2009). · DOI
  7. Freyre, A., Choromanski, L., Fishback, J. L. & Popiel, I. Immunization of cats with tissue cysts, bradyzoites, and tachyzoites of the T-263 strain of Toxoplasma gondii. J. Parasitol. 79, 716–719 (1993). · DOI
  8. Loh, F. K., Nathan, S., Chow, S. C. & Fang, C. M. Vaccination challenges and strategies against long-lived Toxoplasma gondii. Vaccine 37, 3989–4000 (2019). · DOI
  9. Ramakrishnan, C. et al. An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats. Sci. Rep. 9, 1474 (2019). · DOI
  10. Wang, J. L. et al. Live attenuated Pru:Δcdpk2 strain of toxoplasma gondii protects against acute, chronic, and congenital toxoplasmosis. J. Infect. Dis. 218, 768–777 (2018). · DOI
  11. Wang, L., Tang, D., Yang, C., Yang, J. & Fang, R. Toxoplasma gondii ADSL knockout provides excellent immune protection against a variety of strains. Vaccines (Basel) https://doi.org/10.3390/vaccines8010016 (2020). · DOI
  12. Czarnewski, P., Araújo, E. C. B., Oliveira, M. C., Mineo, T. W. P. & Silva, N. M. Recombinant TgHSP70 immunization protects against Toxoplasma gondii brain cyst formation by enhancing inducible nitric oxide expression. Front. Cell Infect. Microbiol. 7, 142 (2017). · DOI
  13. Onile, O. S., Ojo, G. J., Oyeyemi, B. F., Agbowuro, G. O. & Fadahunsi, A. I. Development of multiepitope subunit protein vaccines against Toxoplasma gondii using an immunoinformatics approach. NAR Genom. Bioinform. 2, lqaa048 (2020). · DOI
  14. Foroutan, M. & Ghaffarifar, F. Calcium-dependent protein kinases are potential targets for Toxoplasma gondii vaccine. Clin. Exp. Vaccin. Res. 7, 24–36 (2018). · DOI
  15. Majidiani, H. et al. In-depth computational analysis of calcium-dependent protein kinase 3 of Toxoplasma gondii provides promising targets for vaccination. Clin. Exp. Vaccin. Res. 9, 146–158 (2020). · DOI
  16. Dodangeh, S. et al. Protective efficacy by a novel multi-epitope vaccine, including MIC3, ROP8, and SAG1, against acute Toxoplasma gondii infection in BALB/c mice. Micro. Pathog. 153, 104764 (2021). · DOI
  17. Warner, R. C., Chapman, R. C., Davis, B. N. & Davis, P. H. Review of dna vaccine approaches against the parasite Toxoplasma gondii. J. Parasitol. 107, 882–903 (2021). · DOI
  18. Hiszczyńska-Sawicka, E. et al. Modulation of immune response to Toxoplasma gondii in sheep by immunization with a DNA vaccine encoding ROP1 antigen as a fusion protein with ovine CD154. Vet. Parasitol. 183, 72–78 (2011). · DOI
  19. Parthasarathy, S., Fong, M. Y., Ramaswamy, K. & Lau, Y. L. Protective immune response in BALB/c mice induced by DNA vaccine of the ROP8 gene of Toxoplasma gondii. Am. J. Trop. Med. Hyg. 88, 883–887 (2013). · DOI
  20. Alizadeh, P. et al. IL-17 and IL-22 elicited by a DNA vaccine encoding ROP13 associated with protection against Toxoplasma gondii in BALB/c mice. J. Cell Physiol. 234, 10782–10788 (2019). · DOI
  21. Yuan, Z. G. et al. Protective immunity induced by Toxoplasma gondii rhoptry protein 16 against toxoplasmosis in mice. Clin. Vaccin. immunol. 18, 119–124 (2011). · DOI
  22. Yuan, Z. G. et al. Protective effect against toxoplasmosis in mice induced by DNA immunization with gene encoding Toxoplasma gondii ROP18. Vaccine 29, 6614–6619 (2011). · DOI
  23. Yang, W. B. et al. Vaccination with a DNA vaccine encoding Toxoplasma gondii ROP54 induces protective immunity against toxoplasmosis in mice. Acta Trop. 176, 427–432 (2017). · DOI
  24. Ching, X. T., Fong, M. Y. & Lau, Y. L. Evaluation of the protective effect of deoxyribonucleic acid vaccines encoding granule antigen 2 and 5 against acute toxoplasmosis in BALB/c mice. Am. J. Trop. Med. Hyg. 96, 1441–1447 (2017). · DOI
  25. Zheng, B. et al. GRA24-based DNA vaccine prolongs survival in mice challenged with a virulent Toxoplasma gondii strain. Front. Immunol. 10, 418 (2019). · DOI · Paper page
  26. Rezaei, F. et al. A systematic review on the role of GRA proteins of Toxoplasma gondii in host immunization. J. Microbiol. Methods 165, 105696 (2019). · DOI
  27. Li, Z. Y. et al. Synergy of mIL-21 and mIL-15 in enhancing DNA vaccine efficacy against acute and chronic Toxoplasma gondii infection in mice. Vaccine 32, 3058–3065 (2014). · DOI
  28. Foroutan, M., Zaki, L. & Ghaffarifar, F. Recent progress in microneme-based vaccines development against Toxoplasma gondii. Clin. Exp. Vaccin. Res. 7, 93–103 (2018). · DOI
  29. Pagheh, A. S. et al. Toxoplasma gondii surface antigen 1 (SAG1) as a potential candidate to develop vaccine against toxoplasmosis: A systematic review. Comp. Immunol. Microbiol. Infect. Dis. 69, 101414 (2020). · DOI · Paper page
  30. Myhr, A. I. DNA vaccines: regulatory considerations and safety aspects. Curr. Issues Mol. Biol. 22, 79–88 (2017). · DOI
  31. El Bissati, K. et al. Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A*11:01, HLA-A*02:01 and HLA-B*07:02 transgenic mice. Sci. Rep. 10, 16984 (2020). · DOI
  32. El Bissati, K. et al. Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii. JCI Insight 1, e85955 (2016). · DOI
  33. El Bissati, K. et al. Effectiveness of a novel immunogenic nanoparticle platform for Toxoplasma peptide vaccine in HLA transgenic mice. Vaccine 32, 3243–3248 (2014). · DOI
  34. El Bissati, K. et al. Protein nanovaccine confers robust immunity against Toxoplasma. npj Vaccines 2, 24 (2017). · DOI
  35. Li, Y. & Zhou, H. Moving towards improved vaccines for Toxoplasma gondii. Expert. Opin. Biol. Ther. 18, 273–280 (2018). · DOI
  36. Roozbehani, M. et al. Characterization of a multi-epitope peptide with selective MHC-binding capabilities encapsulated in PLGA nanoparticles as a novel vaccine candidate against Toxoplasma gondii infection. Vaccine 36, 6124–6132 (2018). · DOI · Paper page
  37. Luo, F. et al. Induction of protective immunity against toxoplasma gondii in mice by nucleoside triphosphate hydrolase-II (NTPase-II) self-amplifying RNA vaccine encapsulated in lipid nanoparticle. Front. Microbiol. 8, 605 (2017). · DOI
  38. Sharma, O., Sultan, A. A., Ding, H. & Triggle, C. R. A review of the progress and challenges of developing a vaccine for COVID-19. Front. Immunol. 11, 585354 (2020). · DOI
  39. Pilkington, E. H. et al. From influenza to COVID-19: lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases. Acta Biomater. 131, 16–40 (2021). · DOI
  40. Pardi, N., Hogan, M. J. & Weissman, D. Recent advances in mRNA vaccine technology. Curr. Opin. Immunol. 65, 14–20 (2020). · DOI · Paper page
  41. Maeda, Y. & Kinoshita, T. Structural remodeling, trafficking and functions of glycosylphosphatidylinositol-anchored proteins. Prog. Lipid Res. 50, 411–424 (2011). · DOI
  42. Debierre-Grockiego, F. et al. Activation of TLR2 and TLR4 by glycosylphosphatidylinositols derived from Toxoplasma gondii. J. Immunol. 179, 1129–1137 (2007). · DOI
  43. Astronomo, R. D. & Burton, D. R. Carbohydrate vaccines: developing sweet solutions to sticky situations. Nat. Rev. Drug Discov. 9, 308–324 (2010). · DOI · Paper page
  44. van Niel, G. et al. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 121, 337–349 (2001). · DOI
  45. Théry, C. et al. Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes. Nat. Immunol. 3, 1156–1162 (2002). · DOI
  46. Li, Y. et al. Characterization of exosomes derived from Toxoplasma gondii and their functions in modulating immune responses. Int. J. Nanomed. 13, 467–477 (2018). · DOI
  47. Aline, F., Bout, D., Amigorena, S., Roingeard, P. & Dimier-Poisson, I. Toxoplasma gondii antigen-pulsed-dendritic cell-derived exosomes induce a protective immune response against T. gondii infection. Infect. Immun. 72, 4127–4137 (2004). · DOI
  48. Santos, P. & Almeida, F. Exosome-based vaccines: history, current state, and clinical trials. Front. Immunol. 12, 711565 (2021). · DOI
  49. Yektaeian, N., Malekpour, A., Atapour, A., Davoodi, T. & Hatam, G. Genetic immunization against toxoplasmosis: a review article. Micro. Pathog. 155, 104888 (2021). · DOI
  50. Attias, M. et al. The life-cycle of Toxoplasma gondii reviewed using animations. Parasit. Vectors 13, 588 (2020). · DOI
  51. Cong, H. et al. Human immunome, bioinformatic analyses using HLA supermotifs and the parasite genome, binding assays, studies of human T cell responses, and immunization of HLA-A*1101 transgenic mice including novel adjuvants provide a foundation for HLA-A03 restricted CD8+ T cell epitope based, adjuvanted vaccine protective against Toxoplasma gondii. Immunome Res. 6, 12 (2010). · DOI
  52. Howe, D. K. & Sibley, L. D. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J. Infect. Dis. 172, 1561–1566 (1995). · DOI
  53. Saeij, J. P., Boyle, J. P. & Boothroyd, J. C. Differences among the three major strains of Toxoplasma gondii and their specific interactions with the infected host. Trends Parasitol. 21, 476–481 (2005). · DOI
  54. Khan, A. et al. Genetic analyses of atypical Toxoplasma gondii strains reveal a fourth clonal lineage in North America. Int. J. Parasitol. 41, 645–655 (2011). · DOI
  55. Su, C. et al. Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. Proc. Natl Acad. Sci. USA 109, 5844–5849 (2012). · DOI
  56. Jensen, K. D. et al. Toxoplasma gondii superinfection and virulence during secondary infection correlate with the exact ROP5/ROP18 allelic combination. mBio 6, e02280 (2015). · DOI
  57. Dao, A., Fortier, B., Soete, M., Plenat, F. & Dubremetz, J. F. Successful reinfection of chronically infected mice by a different Toxoplasma gondii genotype. Int. J. Parasitol. 31, 63–65 (2001). · DOI
  58. Feng, G. et al. Human immunization with a polymorphic malaria vaccine candidate induced antibodies to conserved epitopes that promote functional antibodies to multiple parasite strains. J. Infect. Dis. 218, 35–43 (2018). · DOI
  59. Terheggen, U. et al. Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines. BMC Med. 12, 183 (2014). · DOI
  60. Padrão Jda, C., Cabral, G. R., da Silva Mde, F., Seabra, S. H. & DaMatta, R. A. Toxoplasma gondii infection of activated J774-A1 macrophages causes inducible nitric oxide synthase degradation by the proteasome pathway. Parasitol. Int. 63, 659–663 (2014). · DOI
  61. Matta, S. K., Rinkenberger, N., Dunay, I. R. & Sibley, L. D. Toxoplasma gondii infection and its implications within the central nervous system. Nat. Rev. Microbiol. 19, 467–480 (2021). · DOI
  62. Olias, P., Etheridge, R. D., Zhang, Y., Holtzman, M. J. & Sibley, L. D. Toxoplasma effector recruits the Mi-2/NuRD complex to repress STAT1 transcription and block IFN-γ-dependent gene expression. Cell Host Microbe 20, 72–82 (2016). · DOI
  63. Chen, L. et al. The Toxoplasma gondii virulence factor ROP16 acts in cis and trans, and suppresses T cell responses. J. Exp. Med. https://doi.org/10.1084/jem.20181757 (2020). · DOI
  64. Etheridge, R. D. et al. The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice. Cell Host Microbe 15, 537–550 (2014). · DOI
  65. Nadipuram, S. M. et al. In vivo biotinylation of the toxoplasma parasitophorous vacuole reveals novel dense granule proteins important for parasite growth and pathogenesis. mBio https://doi.org/10.1128/mBio.00808-16 (2016). · DOI
  66. Gold, D. A. et al. The toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole. Cell Host Microbe 17, 642–652 (2015). · DOI
  67. Li, T. T. et al. Effect of deletion of gra17 and gra23 genes on the growth, virulence, and immunogenicity of type II Toxoplasma gondii. Parasitol. Res. 119, 2907–2916 (2020). · DOI
  68. Yao, L. et al. Toxoplasma gondii type-I ROP18 targeting human E3 ligase TRIM21 for immune escape. Front. Cell Dev. Biol. 9, 685913 (2021). · DOI
  69. Braun, L. et al. The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2. Nat. Microbiol. 4, 1208–1220 (2019). · DOI
  70. Bernhagen, Jr & Bucala R. Mif Family Cytokines in Innate Immunity and Homeostasis. (Springer International Publishing: Imprint: Springer, 2017).
  71. Ghosh, S., Jiang, N., Farr, L., Ngobeni, R. & Moonah, S. Parasite-produced MIF cytokine: role in immune evasion, invasion, and pathogenesis. Front. Immunol. 10, 1995 (2019). · DOI · Paper page
  72. Tu, V. et al. Enrichment and proteomic characterization of the cyst wall from in vitro Toxoplasma gondii cysts. mBio https://doi.org/10.1128/mBio.00469-19 (2019). · DOI
  73. Waldman, B. S. et al. Identification of a master regulator of differentiation in toxoplasma. Cell 180, 359–372.e316 (2020). · DOI
  74. Sasai, M. & Yamamoto, M. Innate, adaptive, and cell-autonomous immunity against Toxoplasma gondii infection. Exp. Mol. Med. 51, 1–10 (2019). · DOI
  75. Howard, J. C., Hunn, J. P. & Steinfeldt, T. The IRG protein-based resistance mechanism in mice and its relation to virulence in Toxoplasma gondii. Curr. Opin. Microbiol. 14, 414–421 (2011). · DOI
  76. Zhao, X. Y. & Ewald, S. E. The molecular biology and immune control of chronic Toxoplasma gondii infection. J. Clin. Invest. 130, 3370–3380 (2020). · DOI
  77. Subauste, C. S. & Wessendarp, M. Human dendritic cells discriminate between viable and killed Toxoplasma gondii tachyzoites: dendritic cell activation after infection with viable parasites results in CD28 and CD40 ligand signaling that controls IL-12-dependent and -independent T cell production of IFN-gamma. J. Immunol. 165, 1498–1505 (2000). · DOI
  78. Garcia, J. L. et al. Partial protection against tissue cysts formation in pigs vaccinated with crude rhoptry proteins of Toxoplasma gondii. Vet. Parasitol. 129, 209–217 (2005). · DOI
  79. Guerrero Manriquez, G. G. & Tuero, I. Adjuvants: friends in vaccine formulations against infectious diseases. Hum. Vaccines Immunother. 17, 3539–3550 (2021). · DOI
  80. Inclan-Rico, J. M. & Siracusa, M. C. First responders: innate immunity to helminths. Trends Parasitol. 34, 861–880 (2018). · DOI
  81. Buxton, D. Toxoplasmosis: the first commercial vaccine. Parasitol. Today 9, 335–337 (1993). · DOI
  82. Sander, V., Angel, S. O. & Clemente, M. In Prospects of Plant-Based Vaccines in Veterinary Medicine (ed. MacDonald, J.), 89–120. (Springer International Publishing, 2018). · DOI
  83. Sacks D. L., Peters N. C., Bethony J. M. In The Vaccine Book, 2nd edn. (eds. Bloom, B. R. & Lambert, P.-H.), Ch. 17, 331–360. (Academic Press, 2016). · DOI
  84. Sander, V. A. et al. Use of veterinary vaccines for livestock as a strategy to control foodborne parasitic diseases. Front. Cell Infect. Microbiol. 10, 288 (2020). · DOI
  85. Kim, S. Y. & Goldie, S. J. Cost-effectiveness analyses of vaccination programmes: a focused review of modelling approaches. PharmacoEconomics 26, 191–215 (2008). · DOI
  86. Sykes, D. & Rychtář, J. A game-theoretic approach to valuating toxoplasmosis vaccination strategies. Theor. Popul. Biol. 105, 33–38 (2015). · DOI
  87. Bonačić Marinović, A. A. et al. Prospects of toxoplasmosis control by cat vaccination. Epidemics 30, 100380 (2019). · DOI
  88. Innes, E. A., Hamilton, C., Garcia, J. L., Chryssafidis, A. & Smith, D. A one health approach to vaccines against Toxoplasma gondii. Food Waterborne Parasitol. 15, e00053 (2019). · DOI

Cited by

Sorted by citations

Metadata

Authors
Zhang, Y., Li, D., Lu, S., & Zheng, B.
Affiliations
Hangzhou Medical College (CN)
Corresponding author
  • Lu, Shaohong
  • Zheng, Bin
ORCID
Venue
npj Vaccines
Publisher
Springer Science and Business Media LLC
Published
2022-10-31
Volume
7
Issue
1
Pages
131-131
ISSN
2059-0105 (ISSN-L)
DOI
10.1038/s41541-022-00563-0
PMC
PMC9618413
OpenAlex
W4307896339
Cited by
77
References
2
Citations by year
2026: 24 · 2025: 24 · 2024: 18 · 2023: 10 · 2022: 1
FWCI
2.56
Type
journal article
Language
en
Open access
Licence
Locations
  • npj Vaccines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81871684, 32000293)
  • Department of Education of Zhejiang Province
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Coccidia and coccidiosis research
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasitic Infections and Diagnostics
Keywords
toxoplasmosis, Toxoplasma gondii, vaccine development, vaccine candidate, vaccine safety, vaccine efficacy, vaccine durability, clinical translation, parasite life cycle

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review