ArticleHuman vaccines & immunotherapeutics2017
Cysteine mutagenesis improves the production without abrogating antigenicity of a recombinant protein vaccine candidate for human chagas disease.
Article in Human vaccines & immunotherapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- Epitope mapping and conservation of antigens from the Multi-Cruzi immunoassay platform.Medical microbiology and immunology · 2026Article
- Epitope mapping of vaccine antigens Tc24 and TSA1 with antibodies from Trypanosoma cruzi-infected patients.Genes and immunity · 2026Article
- Monospecific antibodies reveal reduction of granulins in frontotemporal dementia caused byMolecular neurodegeneration advances · 2026Article
- Randomized field trial of a therapeutic vaccine against Trypanosoma cruzi natural infection in dogs and correlates for efficacy.NPJ vaccines · 2025Article
- Engineering an indoleamine 2,3-dioxygenase immunotherapyMolecular systems design & engineering · 2025Article
- Mechanistic insights into the structure-based design of a CspZ-targeting Lyme disease vaccine.Nature communications · 2025Article
- Immunomodulatory activity of Trypanosoma cruzi recombinant antigen combination TSA-1-C4 and Tc24-C4 induce activation of macrophages and CD8Parasitology research · 2025Article
- Trypanosoma cruzi Tc24 Antigen Expressed and Orally Delivered by Schizochytrium sp. Microalga is Immunogenic in Mice.Molecular biotechnology · 2024Article
- Immunoglobulin and T cell receptor repertoire changes induced by a prototype vaccine against Chagas disease in naïve rhesus macaques.Journal of biomedical science · 2024Article
- Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease.ACS applied materials & interfaces · 2024Article
- The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection.PLoS neglected tropical diseases · 2023Article
- Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease.Nature communications · 2023Article
- Heterologous mRNA-protein vaccination with Tc24 induces a robust cellular immune response againstCurrent research in immunology · 2023Article
- Vaccine-linked chemotherapy improves cardiac structure and function in a mouse model of chronic Chagas disease.Frontiers in cellular and infection microbiology · 2023Article
- E6020, a TLR4 Agonist Adjuvant, Enhances Both Antibody Titers and Isotype Switching in Response to Immunization with Hapten-Protein Antigens and Is Diminished in Mice with TLR4 Signaling Insufficiency.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Past, present, and future of Lyme disease vaccines: antigen engineering approaches and mechanistic insights.Expert review of vaccines · 2022Review
- Vaccine-linked chemotherapy with a low dose of benznidazole plus a bivalent recombinant protein vaccine prevents the development of cardiac fibrosis caused by Trypanosoma cruzi in chronically-infected BALB/c mice.PLoS neglected tropical diseases · 2022Article
- Use of a small molecule integrin activator as a systemically administered vaccine adjuvant in controlling Chagas disease.NPJ vaccines · 2021Article
- Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.PLoS neglected tropical diseases · 2021Article
- α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model.PLoS neglected tropical diseases · 2021Article
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A therapeutic vaccine for human Chagas disease is under development by the Sabin Vaccine Institute Product Development Partnership. The aim of the vaccine is to significantly reduce the parasite burden of Trypanosoma cruzi in humans, either as a standalone product or in combination with conventional chemotherapy. Vaccination of mice with Tc24 formulated with monophosphoryl-lipid A (MPLA) adjuvant results in a Th1 skewed immune response with elevated IgG2a and IFNγ levels and a statistically significant decrease in parasitemia following T. cruzi challenge. Tc24 was therefore selected for scale-up and further evaluation. During scale up and downstream process development, significant protein aggregation was observed due to intermolecular disulfide bond formation. To prevent protein aggregation, cysteine codons were replaced with serine codons which resulted in the production of a non-aggregated and soluble recombinant protein, Tc24-C4. No changes to the secondary structure of the modified molecule were detected by circular dichroism. Immunization of mice with wild-type Tc24 or Tc24-C4, formulated with E6020 (TLR4 agonist analog to MPLA) emulsified in a squalene-oil-in-water emulsion, resulted in IgG2a and antigen specific IFNγ production levels from splenocytes that were not significantly different, indicating that eliminating putative intermolecular disulfide bonds had no significant impact on the immunogenicity of the molecule. In addition, vaccination with either formulated wild type Tc24 or Tc24-C4 antigen also significantly increased survival and reduced cardiac parasite burden in mice. Investigations are now underway to examine the efficacy of Tc24-C4 formulated with other adjuvants to reduce parasite burden and increase survival in pre-clinical studies.
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