ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease

ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease

Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans -sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi . Herein we generated a chimeric protein c...

Full description

Saved in:
Bibliographic Details
Published in:npj vaccines Vol. 8; no. 1; p. 81
Main Authors: Castro, Julia T., Brito, Rory, Hojo-Souza, Natalia S., Azevedo, Bárbara, Salazar, Natalia, Ferreira, Camila P., Junqueira, Caroline, Fernandes, Ana Paula, Vasconcellos, Ronnie, Cardoso, Jamille M., Aguiar-Soares, Rodrigo D. O., Vieira, Paula M. A., Carneiro, Cláudia M., Valiate, Bruno, Toledo, Cristiane, Salazar, Andres M., Caballero, Otávia, Lannes-Vieira, Joseli, Teixeira, Santuza R., Reis, Alexandre B., Gazzinelli, Ricardo T.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 31-05-2023
Nature Publishing Group
Nature Portfolio
Subjects:
631/250/255/1715
631/250/590/2294
Adenoviruses
Antibodies
Biomedical and Life Sciences
Biomedicine
Chagas disease
Deoxyribonucleic acid
DNA
Immunity (Disease)
Immunization
Immunogenicity
Infectious Diseases
Medical Microbiology
Parasitism
Plasmids
Proteins
Protozoa
Public Health
Vaccine
Vaccines
Vector-borne diseases
Virology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans -sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi . Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi , showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi- specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8 + T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4 + T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8 + T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi . Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-023-00676-0