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IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection

Human ascariasis has a global and cosmopolitan distribution, and has been characterized as the most prevalent neglected tropical disease worldwide. The development of a preventive vaccine is highly desirable to complement current measures required for this parasitic infection control and to reduce c...

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Autores principales: Gazzinelli-Guimarães, Ana Clara, Gazzinelli-Guimarães, Pedro Henrique, Nogueira, Denise Silva, Oliveira, Fabrício Marcus Silva, Barbosa, Fernando Sérgio, Amorim, Chiara Cássia Oliveira, Cardoso, Mariana Santos, Kraemer, Lucas, Caliari, Marcelo Vidigal, Akamatsu, Milena Apetito, Ho, Paulo Lee, Jones, Kathryn Marie, Weatherhead, Jill, Bottazzi, Maria Elena, Hotez, Peter J., Zhan, Bin, Bartholomeu, Daniella Castanheira, Russo, Remo Castro, Bueno, Lilian Lacerda, Fujiwara, Ricardo Toshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238660/
https://www.ncbi.nlm.nih.gov/pubmed/30473693
http://dx.doi.org/10.3389/fimmu.2018.02535
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author Gazzinelli-Guimarães, Ana Clara
Gazzinelli-Guimarães, Pedro Henrique
Nogueira, Denise Silva
Oliveira, Fabrício Marcus Silva
Barbosa, Fernando Sérgio
Amorim, Chiara Cássia Oliveira
Cardoso, Mariana Santos
Kraemer, Lucas
Caliari, Marcelo Vidigal
Akamatsu, Milena Apetito
Ho, Paulo Lee
Jones, Kathryn Marie
Weatherhead, Jill
Bottazzi, Maria Elena
Hotez, Peter J.
Zhan, Bin
Bartholomeu, Daniella Castanheira
Russo, Remo Castro
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
author_facet Gazzinelli-Guimarães, Ana Clara
Gazzinelli-Guimarães, Pedro Henrique
Nogueira, Denise Silva
Oliveira, Fabrício Marcus Silva
Barbosa, Fernando Sérgio
Amorim, Chiara Cássia Oliveira
Cardoso, Mariana Santos
Kraemer, Lucas
Caliari, Marcelo Vidigal
Akamatsu, Milena Apetito
Ho, Paulo Lee
Jones, Kathryn Marie
Weatherhead, Jill
Bottazzi, Maria Elena
Hotez, Peter J.
Zhan, Bin
Bartholomeu, Daniella Castanheira
Russo, Remo Castro
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
author_sort Gazzinelli-Guimarães, Ana Clara
collection PubMed
description Human ascariasis has a global and cosmopolitan distribution, and has been characterized as the most prevalent neglected tropical disease worldwide. The development of a preventive vaccine is highly desirable to complement current measures required for this parasitic infection control and to reduce chronic childhood morbidities. In the present study, we describe the mechanism of protection elicited by a preventive vaccine against ascariasis. Vaccine efficacy was evaluated after immunization with three different Ascaris suum antigen extracts formulated with monophosphoryl lipid A (MPLA) as an adjuvant: crude extract of adult worm (ExAD); crude extract of adult worm cuticle (CUT); and crude extract of infective larvae (L3) (ExL3). Immunogenicity elicited by immunization was assessed by measuring antibody responses, cytokine production, and influx of tissue inflammatory cells. Vaccine efficacy was evaluated by measuring the reductions in the numbers of larvae in the lungs of immunized BALB/c mice that were challenged with A. suum eggs. Moreover, lung physiology and functionality were tested by spirometry to determine clinical efficacy. Finally, the role of host antibody mediated protection was determined by passive transfer of serum from immunized mice. Significant reductions in the total number of migrating larvae were observed in mice immunized with ExL3 61% (p < 0.001), CUT 59% (p < 0.001), and ExAD 51% (p < 0.01) antigens in comparison with non-immunized mice. For the Ascaris antigen-specific IgG antibody levels, a significant and progressive increase was observed with each round of immunization, in association with a marked increase of IgG1 and IgG3 subclasses. Moreover, a significant increase in concentration of IL-5 and IL-10 (pre-challenge) in the blood and IL-10 in the lung tissue (post-challenge) was induced by CUT immunization. Finally, ExL3 and CUT-immunized mice showed a marked improvement in lung pathology and tissue fibrosis as well as reduced pulmonary dysfunction induced by Ascaris challenge, when compared to non-immunized mice. Moreover, the passive transfer of specific IgG antibodies from ExL3, CUT, and ExAD elicited a protective response in naïve mice, with significant reductions in parasite burdens in lungs of 65, 64, and 64%, respectively. Taken together, these studies indicated that IgG antibodies contribute to protective immunity.
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spelling pubmed-62386602018-11-23 IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection Gazzinelli-Guimarães, Ana Clara Gazzinelli-Guimarães, Pedro Henrique Nogueira, Denise Silva Oliveira, Fabrício Marcus Silva Barbosa, Fernando Sérgio Amorim, Chiara Cássia Oliveira Cardoso, Mariana Santos Kraemer, Lucas Caliari, Marcelo Vidigal Akamatsu, Milena Apetito Ho, Paulo Lee Jones, Kathryn Marie Weatherhead, Jill Bottazzi, Maria Elena Hotez, Peter J. Zhan, Bin Bartholomeu, Daniella Castanheira Russo, Remo Castro Bueno, Lilian Lacerda Fujiwara, Ricardo Toshio Front Immunol Immunology Human ascariasis has a global and cosmopolitan distribution, and has been characterized as the most prevalent neglected tropical disease worldwide. The development of a preventive vaccine is highly desirable to complement current measures required for this parasitic infection control and to reduce chronic childhood morbidities. In the present study, we describe the mechanism of protection elicited by a preventive vaccine against ascariasis. Vaccine efficacy was evaluated after immunization with three different Ascaris suum antigen extracts formulated with monophosphoryl lipid A (MPLA) as an adjuvant: crude extract of adult worm (ExAD); crude extract of adult worm cuticle (CUT); and crude extract of infective larvae (L3) (ExL3). Immunogenicity elicited by immunization was assessed by measuring antibody responses, cytokine production, and influx of tissue inflammatory cells. Vaccine efficacy was evaluated by measuring the reductions in the numbers of larvae in the lungs of immunized BALB/c mice that were challenged with A. suum eggs. Moreover, lung physiology and functionality were tested by spirometry to determine clinical efficacy. Finally, the role of host antibody mediated protection was determined by passive transfer of serum from immunized mice. Significant reductions in the total number of migrating larvae were observed in mice immunized with ExL3 61% (p < 0.001), CUT 59% (p < 0.001), and ExAD 51% (p < 0.01) antigens in comparison with non-immunized mice. For the Ascaris antigen-specific IgG antibody levels, a significant and progressive increase was observed with each round of immunization, in association with a marked increase of IgG1 and IgG3 subclasses. Moreover, a significant increase in concentration of IL-5 and IL-10 (pre-challenge) in the blood and IL-10 in the lung tissue (post-challenge) was induced by CUT immunization. Finally, ExL3 and CUT-immunized mice showed a marked improvement in lung pathology and tissue fibrosis as well as reduced pulmonary dysfunction induced by Ascaris challenge, when compared to non-immunized mice. Moreover, the passive transfer of specific IgG antibodies from ExL3, CUT, and ExAD elicited a protective response in naïve mice, with significant reductions in parasite burdens in lungs of 65, 64, and 64%, respectively. Taken together, these studies indicated that IgG antibodies contribute to protective immunity. Frontiers Media S.A. 2018-11-09 /pmc/articles/PMC6238660/ /pubmed/30473693 http://dx.doi.org/10.3389/fimmu.2018.02535 Text en Copyright © 2018 Gazzinelli-Guimarães, Gazzinelli-Guimarães, Nogueira, Oliveira, Barbosa, Amorim, Cardoso, Kraemer, Caliari, Akamatsu, Ho, Jones, Weatherhead, Bottazzi, Hotez, Zhan, Bartholomeu, Russo, Bueno and Fujiwara. http://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
Gazzinelli-Guimarães, Pedro Henrique
Nogueira, Denise Silva
Oliveira, Fabrício Marcus Silva
Barbosa, Fernando Sérgio
Amorim, Chiara Cássia Oliveira
Cardoso, Mariana Santos
Kraemer, Lucas
Caliari, Marcelo Vidigal
Akamatsu, Milena Apetito
Ho, Paulo Lee
Jones, Kathryn Marie
Weatherhead, Jill
Bottazzi, Maria Elena
Hotez, Peter J.
Zhan, Bin
Bartholomeu, Daniella Castanheira
Russo, Remo Castro
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection
title IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection
title_full IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection
title_fullStr IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection
title_full_unstemmed IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection
title_short IgG Induced by Vaccination With Ascaris suum Extracts Is Protective Against Infection
title_sort igg induced by vaccination with ascaris suum extracts is protective against infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238660/
https://www.ncbi.nlm.nih.gov/pubmed/30473693
http://dx.doi.org/10.3389/fimmu.2018.02535
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