Therapeutic effects of vaccine derived from amastigote surface protein-2 (ASP-2) against Chagas disease in mouse liver

Ribeiro, Flávia Andressa Pidone; Ferreira, Camila Pontes; Gazzinelli, Ricardo T.; Bruna-Romero, Oscar; Lazzarin, Mariana Cruz; Santos, José Fontes dos; Oliveira, Flávia de; Pisani, Luciana Pellegrini; Vasconcelos, José Ronnie; Ribeiro, Daniel Araki

doi:10.1016/j.cyto.2018.07.017

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…cruzi throughout its life cycle. Previous evaluations of these antigens as individual vaccine candidates had already yielded promising results. ,− In this study, we assessed the efficacy of our therapeutic vaccination strategy in vivo, which involved administering three doses of either the monovalent or the bivalent mRNA vaccines at 70, 77, and 84 DPI. The spleen, characterized by the presence of various leukocyte populations, including T cells, B cells, DCs, and macrophages, plays a crucial role in immune response regulation, encompassing innate and adaptive immune system responses .…”

Section: Resultsmentioning

confidence: 99%

Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Mancino,

Pollet,

Zinger

et al. 2024

ACS Appl. Mater. Interfaces

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Chagas disease (CD) (American trypanosomiasis caused by Trypanosoma cruzi) is a parasitic disease endemic in 21 countries in South America, with increasing global spread. When administered late in the infection, the current antiparasitic drugs do not prevent the onset of cardiac illness leading to chronic Chagasic cardiomyopathy. Therefore, new therapeutic vaccines or immunotherapies are under development using multiple platforms. In this study, we assessed the feasibility of developing an mRNA-based therapeutic CD vaccine targeting two known T. cruzi vaccine antigens (Tc24�a flagellar antigen and ASP-2�an amastigote antigen). We present the mRNA engineering steps, preparation, and stability of the lipid nanoparticles and evaluation of their uptake by dendritic cells, as well as their biodistribution in c57BL/J mice. Furthermore, we assessed the immunogenicity and efficacy of two mRNA-based candidates as monovalent and bivalent vaccine strategies using an in vivo chronic mouse model of CD. Our results show several therapeutic benefits, including reductions in parasite burdens and cardiac inflammation, with each mRNA antigen, especially with the mRNA encoding Tc24, and Tc24 in combination with ASP-2. Therefore, our findings demonstrate the potential of mRNA-based vaccines as a therapeutic option for CD and highlight the opportunities for developing multivalent vaccines using this approach.

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Section: Resultsmentioning

confidence: 99%

Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Mancino,

Pollet,

Zinger

et al. 2024

ACS Appl. Mater. Interfaces

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“…This observation provides insight as to why delayed therapy after the onset of cardiac symptoms might be more beneficial. Two other reports demonstrate this vaccine’s efficacy when vaccination and challenge occur simultaneously [ 119 , 122 ]. Given that many infected individuals present as asymptomatic and their seropositivity will be unknown, the relevancy of these studies in a clinical setting is questionable; however, they can provide insight into the early immune responses to T. cruzi infection.…”

Section: Adenovirus-vectored Vaccines Against Chagas Diseasementioning

confidence: 93%

“…Research groups from Brazilian universities, in collaboration with the University of Massachusetts, Worchester, have published a significant body of work investigating AdV-vectored vaccines for Chagas disease in murine models. They have developed HAdV-5 vectors expressing T. cruzi amastigote surface protein-2 (ASP2) and/or trans-sialidase (TS) [ 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ]. It was found that immunization with both AdV-ASP2 and AdV-TS vaccines together provided 100% survival against T. cruzi Y strain in BALB/c and C57BL/6 mice when challenged four weeks post-vaccination.…”

Section: Adenovirus-vectored Vaccines Against Chagas Diseasementioning

confidence: 99%

Recent Advances in the Development of Adenovirus-Vectored Vaccines for Parasitic Infections

2023

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Vaccines against parasites have lagged centuries behind those against viral and bacterial infections, despite the devastating morbidity and widespread effects of parasitic diseases across the globe. One of the greatest hurdles to parasite vaccine development has been the lack of vaccine strategies able to elicit the complex and multifaceted immune responses needed to abrogate parasitic persistence. Viral vectors, especially adenovirus (AdV) vectors, have emerged as a potential solution for complex disease targets, including HIV, tuberculosis, and parasitic diseases, to name a few. AdVs are highly immunogenic and are uniquely able to drive CD8+ T cell responses, which are known to be correlates of immunity in infections with most protozoan and some helminthic parasites. This review presents recent developments in AdV-vectored vaccines targeting five major human parasitic diseases: malaria, Chagas disease, schistosomiasis, leishmaniasis, and toxoplasmosis. Many AdV-vectored vaccines have been developed for these diseases, utilizing a wide variety of vectors, antigens, and modes of delivery. AdV-vectored vaccines are a promising approach for the historically challenging target of human parasitic diseases.

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“…Others propose that the potential synergistic immunologic advantage of a mixture of epitopes from a family with several genes would encourage an elevated frequency of immune effectors in heterogeneous host populations and will offer effective immunity against distinct parasite strains [119]. Accordingly, members of the TS superfamily, including, trypomastigote surface antigen (TSA-1), TS, and amastigote surface proteins (ASP-1, ASP-2, ASP-9) were considered as potential vaccine candidates because they have been shown to be recognized by antibody response and CD8 + T lymphocytes in infected mice and humans [126][127][128][129][130][131][132][133][134][135]. Other antigens, including complement regulatory protein [136,137], lysosomal cysteine proteinase (cruzipain) [138,139], flagellar calcium-binding protein [140,141], GP90 and GP82 [142][143][144][145], kinetoplastid membrane protein 11 [146][147][148], LYT1 [149], paraflagellar rod proteins [150][151][152][153], Tc52 (glutathione S-transferases) [154] etc.…”

Section: Efforts For Preventive/therapeutic Vaccine Development Againmentioning

confidence: 99%

Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital Chagas disease

Rios¹,

Campos²,

Menon³

et al. 2020

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Therapeutic effects of vaccine derived from amastigote surface protein-2 (ASP-2) against Chagas disease in mouse liver

Cited by 8 publications

References 38 publications

Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Recent Advances in the Development of Adenovirus-Vectored Vaccines for Parasitic Infections

Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital Chagas disease

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