"Immunoinformatic Identification of T-Cell and B-Cell Epitopes From Giardia lamblia Immunogenic Proteins as Candidates to Develop Peptide-Based Vaccines Against Giardiasis".

Thania Garzon,David Ortega-Tirado,Gloria Lopez-Romero,Carlos Velazquez,Efrain Alday,Adriana Garibay-Escobar,Ramón Enrique Robles-Zepeda

doi:10.3389/fcimb.2021.769446

Thania Garzon, David Ortega-Tirado + Show 5 more

Open Access

https://doi.org/10.3389/fcimb.2021.769446

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Abstract

Giardiasis is one of the most common gastrointestinal infections worldwide, mainly in developing countries. The etiological agent is the Giardia lamblia parasite. Giardiasis mainly affects children and immunocompromised people, causing symptoms such as diarrhea, dehydration, abdominal cramps, nausea, and malnutrition. In order to develop an effective vaccine against giardiasis, it is necessary to understand the host-Giardia interactions, the immunological mechanisms involved in protection against infection, and to characterize the parasite antigens that activate the host immune system. In this study, we identify and characterize potential T-cell and B-cell epitopes of Giardia immunogenic proteins by immunoinformatic approaches, and we discuss the potential role of those epitopes to stimulate the host´s immune system. We selected the main immunogenic and protective proteins of Giardia experimentally investigated. We predicted T-cell and B-cell epitopes using immunoinformatic tools (NetMHCII and BCPREDS). Variable surface proteins (VSPs), structural (giardins), metabolic, and cyst wall proteins were identified as the more relevant immunogens of G. lamblia. We described the protein sequences with the highest affinity to bind MHC class II molecules from mouse (I-Ak and I-Ad) and human (DRB1*03:01 and DRB1*13:01) alleles, as well as we selected promiscuous epitopes, which bind to the most common range of MHC class II molecules in human population. In addition, we identified the presence of conserved epitopes within the main protein families (giardins, VSP, CWP) of Giardia. To our knowledge, this is the first in silico study that analyze immunogenic proteins of G. lamblia by combining bioinformatics strategies to identify potential T-cell and B-cell epitopes, which can be potential candidates in the development of peptide-based vaccines. The bioinformatics analysis demonstrated in this study provides a deeper understanding of the Giardia immunogens that bind to critical molecules of the host immune system, such as MHC class II and antibodies, as well as strategies to rational design of peptide-based vaccine against giardiasis.

Highlights

Giardiasis is a highly prevalent foodborne gastrointestinal parasitic infection in developing countries, mainly affecting children and immunocompromised individuals
The identification and selection of immunogenic antigens from Giardia was performed on the scientific platform NCBI (PubMed: http://www.ncbi.nlm.nih.gov/pubmed/) by filtering the results to the last 30 years, using several keywords to identify the potential articles, including: Giardia lamblia, immunogenic proteins, protection, immune response, vaccine, variant-surface proteins (VSPs), giardins, and cyst wall proteins (CWPs)
The proteins presented a homology > 78% between assemblages, unlike for VSPs, due the expressed VSPs are different between the trophozoites of assemblages A and B. (Franzén et al, 2009)

Summary

Introduction

Giardiasis is a highly prevalent foodborne gastrointestinal parasitic infection in developing countries, mainly affecting children and immunocompromised individuals. G. lamblia has a simple life cycle, consisting of two different developmental stages defined by specific structural and biochemical features, wherein the cyst is the infective form, whereas the trophozoite is the proliferative form that colonizes the upper tract of small intestine (Lujan, 2006; Cedillo-Rivera et al, 2009; Ankarklev et al, 2010; Lopez-Romero et al, 2015). The establishment of endoparasitic infections rely on the intricate molecular interaction between each specific stage of the life cycle of parasites and the immune responses of their hosts (Tedla et al, 2019; Smith et al, 2021). The integration of innate and adaptive immune responses defines the fate of parasitic infections, immunocompetence, immunopolymorphism and immunological memory of the host are important for the resolution of parasitic infections (Lima and Lodoen, 2019; Mukherjee et al, 2019)

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