ArticlePLoS neglected tropical diseases2017
Immunization with Tc52 or its amino terminal domain adjuvanted with c-di-AMP induces Th17+Th1 specific immune responses and confers protection against Trypanosoma cruzi.
Article in PLoS neglected tropical diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Mucosal immunity and vaccine development.Signal transduction and targeted therapy · 2026Pooled it
- Characterization of a transmembrane-activating STING agonist using genetically humanized mice.Cell reports · 2026Article
- Long-Lasting Antibody and CD8Vaccines · 2026Article
- Protective immunity against Chagas disease induced by a superantigen-based chimeric DNA vaccine delivered by attenuatedFrontiers in immunology · 2026Article
- Intranasal delivery of a COBRA-based protein vaccine adjuvanted with c-di-AMP enhances breadth of protective immune responses against seasonal influenza viruses.Frontiers in immunology · 2026Article
- Advances and prospects of respiratory mucosal vaccines: mechanisms, technologies, and clinical applications.NPJ vaccines · 2025Review
- Comparative molecular, innate, and adaptive impacts of chemically diverse STING agonists.Vaccine · 2025Review
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- Intranasal Trans-Sialidase Vaccine Mitigates Acute and Chronic Pathology in a Preclinical Oral Chagas Disease Model.Vaccines · 2024Article
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- New Generation Self-Replicating RNA Vaccines Derived from Pestivirus Genome.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Nucleotides as Bacterial Second Messengers.Molecules (Basel, Switzerland) · 2023Review
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- Function and regulation of cGAS-STING signaling in infectious diseases.Frontiers in immunology · 2023Review
- Development of Nasal Vaccines and the Associated Challenges.Pharmaceutics · 2022Review
- Review
- Intranasal COVID-19 vaccines: From bench to bed.EBioMedicine · 2022Review
- The role of bacterial cyclic di-adenosine monophosphate in the host immune response.Frontiers in microbiology · 2022Review
- The Promise and Challenges of Cyclic Dinucleotides as Molecular Adjuvants for Vaccine Development.Vaccines · 2021Review
- Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of new adjuvants enables fine modulation of the elicited immune responses. Ideally, the use of one or more adjuvants should result in the induction of a protective immune response against the specific pathogen. We have evaluated the immune response and protection against Trypanosoma cruzi infection in mice vaccinated with recombinant Tc52 or its N- and C-terminal domains (NTc52 and CTc52) adjuvanted either with the STING (Stimulator of Interferon Genes) agonist cyclic di-AMP (c-di-AMP), a pegylated derivative of α-galactosylceramide (αGC-PEG), or oligodeoxynucleotides containing unmethylated CpG motifs (ODN-CpG). All groups immunized with the recombinant proteins plus adjuvant: Tc52+c-di-AMP, NTc52+c-di-AMP, CTc52+c-di-AMP, NTc52+c-di-AMP+αGC-PEG, NTc52+CpG, developed significantly higher anti-Tc52 IgG titers than controls. Groups immunized with c-di-AMP and Tc52, NTc52 or CTc52 showed the highest Tc52-specific IgA titers in nasal lavages. All groups immunized with the recombinant proteins plus adjuvant developed a strong specific cellular immune response in splenocytes and lymph node cells with significant differences for groups immunized with c-di-AMP and Tc52, NTc52 or CTc52. These groups also showed high levels of Tc52-specific IL-17 and IFN-γ producing cells, while NTc52+CpG group only showed significant difference with control in IFN-γ producing cells. Groups immunized with c-di-AMP and Tc52, NTc52 or CTc52 developed predominantly a Th17 and Th1immune response, whereas for NTc52+CpG it was a dominant Th1 response. It was previously described that αGC-PEG inhibits Th17 differentiation by activating NKT cells. Thus, in this work we have also included a group immunized with both adjuvants (NTc52+c-di-AMP+αGC-PEG) with the aim to modulate the Th17 response induced by c-di-AMP. This group showed a significant reduction in the number of Tc52-specific IL-17 producing splenocytes, as compared to the group NTc52+c-di-AMP, which has in turn correlated with a reduction in protection against infection. These results suggest that the Th17 immune response developed after immunizing with NTc52+c-di-AMP could have a protective role against T. cruzi infection. Groups NTc52+c-di-AMP, Tc52+c-di-AMP and NTc52PB, were the ones that showed better protection against infection with lower parasitemia and weight loss, and higher survival.
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