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ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection

Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The de...

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Autores principales: Gazzinelli-Guimarães, Ana Clara, Nogueira, Denise Silva, Amorim, Chiara Cássia Oliveira, Oliveira, Fabrício Marcus Silva, Coqueiro-Dos-Santos, Anderson, Carvalho, Samuel Alexandre Pimenta, Kraemer, Lucas, Barbosa, Fernando Sérgio, Fraga, Vanessa Gomes, Santos, Flaviane Vieira, de Castro, Joseane Camilla, Russo, Remo Castro, Akamatsu, Milena Apetito, Ho, Paulo Lee, Bottazzi, Maria Elena, Hotez, Peter J., Zhan, Bin, Bartholomeu, Daniella Castanheira, Bueno, Lilian Lacerda, Fujiwara, Ricardo Toshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724438/
https://www.ncbi.nlm.nih.gov/pubmed/34992603
http://dx.doi.org/10.3389/fimmu.2021.788185
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author Gazzinelli-Guimarães, Ana Clara
Nogueira, Denise Silva
Amorim, Chiara Cássia Oliveira
Oliveira, Fabrício Marcus Silva
Coqueiro-Dos-Santos, Anderson
Carvalho, Samuel Alexandre Pimenta
Kraemer, Lucas
Barbosa, Fernando Sérgio
Fraga, Vanessa Gomes
Santos, Flaviane Vieira
de Castro, Joseane Camilla
Russo, Remo Castro
Akamatsu, Milena Apetito
Ho, Paulo Lee
Bottazzi, Maria Elena
Hotez, Peter J.
Zhan, Bin
Bartholomeu, Daniella Castanheira
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
author_facet Gazzinelli-Guimarães, Ana Clara
Nogueira, Denise Silva
Amorim, Chiara Cássia Oliveira
Oliveira, Fabrício Marcus Silva
Coqueiro-Dos-Santos, Anderson
Carvalho, Samuel Alexandre Pimenta
Kraemer, Lucas
Barbosa, Fernando Sérgio
Fraga, Vanessa Gomes
Santos, Flaviane Vieira
de Castro, Joseane Camilla
Russo, Remo Castro
Akamatsu, Milena Apetito
Ho, Paulo Lee
Bottazzi, Maria Elena
Hotez, Peter J.
Zhan, Bin
Bartholomeu, Daniella Castanheira
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
author_sort Gazzinelli-Guimarães, Ana Clara
collection PubMed
description Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The development of a vaccine that reduces the intensity of infection and maintains lower morbidity should be the primary target for infection control. Previously, our group demonstrated that immunization with crude Ascaris antigens in mice induced an IgG-mediated protective response with significant worm reduction. Here, we aimed to develop a multipeptide chimera vaccine based on conserved B-cell epitopes predicted from 17 common helminth proteomes using a bioinformatics algorithm. More than 480 B-cell epitopes were identified that are conserved in all 17 helminths. The Ascaris-specific epitopes were selected based on their reactivity to the pooled sera of mice immunized with Ascaris crude antigens or infected three times with A. suum infective eggs. The top 35 peptides with the strongest reactivity to Ascaris immune serum were selected to construct a chimeric antigen connected in sequence based on conformation. This chimera, called ASCVac-1, was produced as a soluble recombinant protein in an Escherichia coli expression system and, formulated with MPLA, was used to immunize mice. Mice immunized with ASCVac-1/MPLA showed around 50% reduced larvae production in the lungs after being challenged with A. suum infective eggs, along with significantly reduced inflammation and lung tissue/function damage. The reduced parasite count and pathology in infected lungs were associated with strong Th2 immune responses characterized by the high titers of antigen-specific IgG and its subclasses (IgG1, IgG2a, and IgG3) in the sera and significantly increased IL-4, IL-5, IL-13 levels in lung tissues. The reduced IL-33 titers and stimulated eosinophils were also observed in lung tissues and may also contribute to the ASCVac-1-induced protection. Taken together, the preclinical trial with ASCVac-1 chimera in a mouse model demonstrated its significant vaccine efficacy associated with strong IgG-based Th2 responses, without IgE induction, thus reducing the risk of an allergic response. All results suggest that the multiepitope-based ASCVac-1 chimera is a promising vaccine candidate against Ascaris sp. infections.
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spelling pubmed-87244382022-01-05 ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection Gazzinelli-Guimarães, Ana Clara Nogueira, Denise Silva Amorim, Chiara Cássia Oliveira Oliveira, Fabrício Marcus Silva Coqueiro-Dos-Santos, Anderson Carvalho, Samuel Alexandre Pimenta Kraemer, Lucas Barbosa, Fernando Sérgio Fraga, Vanessa Gomes Santos, Flaviane Vieira de Castro, Joseane Camilla Russo, Remo Castro Akamatsu, Milena Apetito Ho, Paulo Lee Bottazzi, Maria Elena Hotez, Peter J. Zhan, Bin Bartholomeu, Daniella Castanheira Bueno, Lilian Lacerda Fujiwara, Ricardo Toshio Front Immunol Immunology Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The development of a vaccine that reduces the intensity of infection and maintains lower morbidity should be the primary target for infection control. Previously, our group demonstrated that immunization with crude Ascaris antigens in mice induced an IgG-mediated protective response with significant worm reduction. Here, we aimed to develop a multipeptide chimera vaccine based on conserved B-cell epitopes predicted from 17 common helminth proteomes using a bioinformatics algorithm. More than 480 B-cell epitopes were identified that are conserved in all 17 helminths. The Ascaris-specific epitopes were selected based on their reactivity to the pooled sera of mice immunized with Ascaris crude antigens or infected three times with A. suum infective eggs. The top 35 peptides with the strongest reactivity to Ascaris immune serum were selected to construct a chimeric antigen connected in sequence based on conformation. This chimera, called ASCVac-1, was produced as a soluble recombinant protein in an Escherichia coli expression system and, formulated with MPLA, was used to immunize mice. Mice immunized with ASCVac-1/MPLA showed around 50% reduced larvae production in the lungs after being challenged with A. suum infective eggs, along with significantly reduced inflammation and lung tissue/function damage. The reduced parasite count and pathology in infected lungs were associated with strong Th2 immune responses characterized by the high titers of antigen-specific IgG and its subclasses (IgG1, IgG2a, and IgG3) in the sera and significantly increased IL-4, IL-5, IL-13 levels in lung tissues. The reduced IL-33 titers and stimulated eosinophils were also observed in lung tissues and may also contribute to the ASCVac-1-induced protection. Taken together, the preclinical trial with ASCVac-1 chimera in a mouse model demonstrated its significant vaccine efficacy associated with strong IgG-based Th2 responses, without IgE induction, thus reducing the risk of an allergic response. All results suggest that the multiepitope-based ASCVac-1 chimera is a promising vaccine candidate against Ascaris sp. infections. Frontiers Media S.A. 2021-12-21 /pmc/articles/PMC8724438/ /pubmed/34992603 http://dx.doi.org/10.3389/fimmu.2021.788185 Text en Copyright © 2021 Gazzinelli-Guimarães, Nogueira, Amorim, Oliveira, Coqueiro-Dos-Santos, Carvalho, Kraemer, Barbosa, Fraga, Santos, de Castro, Russo, Akamatsu, Ho, Bottazzi, Hotez, Zhan, Bartholomeu, Bueno and Fujiwara https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Gazzinelli-Guimarães, Ana Clara
Nogueira, Denise Silva
Amorim, Chiara Cássia Oliveira
Oliveira, Fabrício Marcus Silva
Coqueiro-Dos-Santos, Anderson
Carvalho, Samuel Alexandre Pimenta
Kraemer, Lucas
Barbosa, Fernando Sérgio
Fraga, Vanessa Gomes
Santos, Flaviane Vieira
de Castro, Joseane Camilla
Russo, Remo Castro
Akamatsu, Milena Apetito
Ho, Paulo Lee
Bottazzi, Maria Elena
Hotez, Peter J.
Zhan, Bin
Bartholomeu, Daniella Castanheira
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection
title ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection
title_full ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection
title_fullStr ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection
title_full_unstemmed ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection
title_short ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection
title_sort ascvac-1, a multi-peptide chimeric vaccine, protects mice against ascaris suum infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724438/
https://www.ncbi.nlm.nih.gov/pubmed/34992603
http://dx.doi.org/10.3389/fimmu.2021.788185
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