Expression, purification, immunogenicity, and protective efficacy of a recombinant Tc24 antigen as a vaccine against Trypanosoma cruzi infection in mice

Martínez-Campos, Viridiana; Martínez-Vega, Pedro Pablo; Ramírez-Sierra, María Jesús; Rosado-Vallado, Miguel; Seid, Christopher A.; Hudspeth, Elissa M.; Wei, Junfei; Liu, Zhuyun; Kwityn, Cliff; Hammond, Molly; Ortega‐López, Jaime; Zhan, Bin; Hotez, Peter J.; Bottazzi, María Elena; Dumonteil, Eric

doi:10.1016/j.vaccine.2015.07.017

Cited by 50 publications

(57 citation statements)

References 32 publications

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“…[48][49][50] Other therapeutic vaccines against Chagas disease have been found to induce a protective antigen-specific CD8 C T cell population that expands upon challenge with infection and produces T H 1-associated cytokines that include IFNg and TNFa, 51 as well as a CD4 C T cell population capable of IFNg production. 24 Our results are consistent with these findings, though further characterization of the immune response could be pursued to determine the cell types responsible for protection in this model.…”

Section: Discussionsupporting

confidence: 87%

“…Studies testing efficacy of the Tc24 DNA vaccine showed protection in both an acute and a chronic mouse model of disease. 22,24 Therefore, we anticipate that our findings of therapeutic efficacy here will predict efficacy in a chronic model of disease. Ultimately, vaccine development is a stepwise process and using the acute model for screening vaccine candidates can be used as an effective in vivo model to determine whether a vaccine would stimulate a sufficient immune response to control parasitemia, and is frequently used in drug efficacy testing.…”

Section: Discussionmentioning

confidence: 97%

“…Our findings of parasite reduction, but not elimination, are similar to the majority of Chagas disease vaccine studies. 24,25,29 Though sterilizing immunity may not be achievable in this model, it is clear that a successful vaccine will need to produce a meaningful reduction in parasitemia. Ultimately, Tc24 may be combined with other T. cruzi antigens, such as TSA1, TcG2, and TcG4 to increase vaccine efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Ultimately, Tc24 may be combined with other T. cruzi antigens, such as TSA1, TcG2, and TcG4 to increase vaccine efficacy. 22,24,29,30,58 Additionally, this vaccine could potentially be tested in combination with reduced dose chemotherapy. 15 If the vaccine provides a dose-sparing effect on the chemotherapeutic agents, the side effect profile could be minimized while increasing efficacy though multiple parasite killing mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…This recombinant protein was found to be immunogenic and partially protective as a prophylactic vaccine in mice when formulated with the Toll-like receptor 4 (TLR-4) agonist monophosphoryl lipid A. 24 In humans, recombinant Tc24 has been utilized as an antigen for serodiagnosis of Chagas disease and as a tool to monitor treatment success, 25,26 and T cell epitopes have been investigated. 11 Multiple studies have demonstrated that a T H 1-mediated CD8 C T cell response is required for protective immunity to T. cruzi.…”

Section: Introductionmentioning

confidence: 99%

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A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

Barry

Wang

Jones

et al. 2016

Human Vaccines & Immunotherapeutics

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Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust T H 1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a T H 1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNg-producing splenocytes, IgG2a titers, and proliferative capacity of CD8 C T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

Barry

Wang

Jones

et al. 2016

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

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Microalgae‐made human vaccines and therapeutics: A decade of advances

Trujillo,

Monreal‐Escalante,

Angulo

2024

Biotechnology Journal

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Microalgal emergence is a promising platform with two‐decade historical background for producing vaccines and biopharmaceuticals. During that period, microalgal‐based vaccines have reported successful production for various diseases. Thus, species selection is important for genetic transformation and delivery methods that have been developed. Although many vaccine prototypes have been produced for infectious and non‐infectious diseases, fewer studies have reached immunological and immunoprotective evaluations. Microalgae‐made vaccines for Staphylococcus aureus, malaria, influenza, human papilloma, and Zika viruses have been explored in their capacity to induce humoral or cellular immune responses and protective efficacies against experimental challenges. Therefore, specific pathogen antigens and immune system role are important and addressed in controlling these infections. Regarding non‐communicable diseases, these vaccines have been investigated for breast cancer; microalgal‐produced therapeutic molecules and microalgal‐made interferon‐α have been explored for hypertension and potential applications in treating viral infections and cancer, respectively. Thus, conducting immunological trials is emphasized, discussing the promising results observed in terms of immunogenicity, desired immune response for controlling affections, and challenges for achieving the desired protection levels. The potential advantages and hurdles associated with this innovative approach are highlighted, underlining the relevance of assessing immune responses in preclinical and clinical trials to validate the efficacy of these biopharmaceuticals. The promising future of this healthcare technology is also envisaged.

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Trypanosoma cruzi Tc24 Antigen Expressed and Orally Delivered by Schizochytrium sp. Microalga is Immunogenic in Mice

et al. 2023

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Expression, purification, immunogenicity, and protective efficacy of a recombinant Tc24 antigen as a vaccine against Trypanosoma cruzi infection in mice

Cited by 50 publications

References 32 publications

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

Microalgae‐made human vaccines and therapeutics: A decade of advances

Trypanosoma cruzi Tc24 Antigen Expressed and Orally Delivered by Schizochytrium sp. Microalga is Immunogenic in Mice

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