Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Unraveling the potential of Giardia extracellular vesicles as a vaccine candidat

Clarissa Pérez Faria
,
Sandra Jesus
ORCID logo ,
Ágata Lourenço
ORCID logo ,
Bárbara Ferreira
,
Ana Isabel
ORCID logo ,
Daniela Mateus
,
Bruno Neves
ORCID logo ,
Teresa Rosete
ORCID logo ,
Olga Borges
* ORCID logo ,
Maria Do Céu Sousa
* ORCID logo
Version 1 : Received: 13 March 2024 / Approved: 14 March 2024 / Online: 14 March 2024 (09:49:02 CET)

How to cite: Faria, C.P.; Jesus, S.; Lourenço, Á.; Ferreira, B.; Isabel, A.; Mateus, D.; Neves, B.; Rosete, T.; Borges, O.; Sousa, M.D.C. Unraveling the potential of Giardia extracellular vesicles as a vaccine candidat. Preprints 2024, 2024030845. https://doi.org/10.20944/preprints202403.0845.v1 Faria, C.P.; Jesus, S.; Lourenço, Á.; Ferreira, B.; Isabel, A.; Mateus, D.; Neves, B.; Rosete, T.; Borges, O.; Sousa, M.D.C. Unraveling the potential of Giardia extracellular vesicles as a vaccine candidat. Preprints 2024, 2024030845. https://doi.org/10.20944/preprints202403.0845.v1

Abstract

In this study, we investigated the role of Giardia EVs in cellular communication and their potential as vaccine candidates. Our findings revealed that Giardia EVs activate pro-inflammatory signalling cascades, including SAPK/JNK and ERK1/ERK2, as well as the NF-kB pathway, resulting in IκB-α degradation and p65 translocation to the nucleus, in mouse macrophages. Moreover, Giardia EVs increased the expression of genes encoding pro-inflammatory molecules, such as Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf. Interestingly, Giardia EVs enhanced the maturation status of human Mo-DCs and significantly increased T-cell proliferation with a Th1 profile. Immunization studies demonstrated that Giardia EVs elicited antigen-specific antibodies, with IgG subclasses indicating a balance Th1/ Th2 response. Mass spectrometry analysis identified EV proteins (22 KDa and 50 KDa) that bind to serum antibodies of immunized mice including elongation factor 1-alpha, Alpha-7.3 giardin, tubulin, and Variant Surface Proteins (VSP), known antigenic proteins in Giardia infections. Overall, our results indicated that Giardia EVs modulate innate immune cells in vitro, induce antibody-based immune response in vivo, and contain conserved immunogenic proteins. Consequently, Giardia EVs hold promise as a cell-free vaccine candidate for giardiasis.

Keywords

giardiasis; exossomes; microvesicles; macrophage; dendritic cells; in vivo; immune response

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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