Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection.
BACKGROUND:Ascaris lumbricoides is one of the three major soil-transmitted gastrointestinal helminths (STHs) that infect more than 440 million people in the world, ranking this neglected tropical disease among the most common afflictions of people living in poverty. Children infected with this round...
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ftdoajarticles:oai:doaj.org/article:259b44782ea34685a5c28199b05f9587 2023-05-15T15:16:01+02:00 Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection. Leroy Versteeg Junfei Wei Zhuyun Liu Brian Keegan Ricardo T Fujiwara Kathryn M Jones Oluwatoyin Asojo Ulrich Strych Maria Elena Bottazzi Peter J Hotez Bin Zhan 2020-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008057 https://doaj.org/article/259b44782ea34685a5c28199b05f9587 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008057 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008057 https://doaj.org/article/259b44782ea34685a5c28199b05f9587 PLoS Neglected Tropical Diseases, Vol 14, Iss 2, p e0008057 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008057 2022-12-31T09:15:14Z BACKGROUND:Ascaris lumbricoides is one of the three major soil-transmitted gastrointestinal helminths (STHs) that infect more than 440 million people in the world, ranking this neglected tropical disease among the most common afflictions of people living in poverty. Children infected with this roundworm suffer from malnutrition, growth stunting as well as cognitive and intellectual deficits. An effective vaccine is urgently needed to complement anthelmintic deworming as a better approach to control helminth infections. As37 is an immunodominant antigen of Ascaris suum, a pig roundworm closely related to the human A. lumbricoides parasite, recognized by protective immune sera from A. suum infected mice. In this study, the immunogenicity and vaccine efficacy of recombinant As37 were evaluated in a mouse model. METHODOLOGY/PRINCIPAL FINDINGS:As37 was cloned and expressed as a soluble recombinant protein (rAs37) in Escherichia coli. The expressed rAs37 was highly recognized by protective immune sera from A. suum egg-infected mice. Balb/c mice immunized with 25 μg rAs37 formulated with AddaVax™ adjuvant showed significant larval worm reduction after challenge with A. suum infective eggs when compared with a PBS (49.7%) or adjuvant control (48.7%). Protection was associated with mixed Th1/2-type immune responses characterized by high titers of serological IgG1 and IgG2a and stimulation of the production of cytokines IL-4, IL-5, IL-10 and IL-13. In this experiment, the AddaVax™ adjuvant induced better protection than the Th1-type adjuvant MPLA (38.9%) and the Th2-type adjuvant Alhydrogel (40.7%). Sequence analysis revealed that As37 is a member of the immunoglobulin superfamily (IgSF) and highly conserved in other human STHs. Anti-As37 antibodies strongly recognized homologs in hookworms (Necator americanus, Ancylostoma ceylanicum, A. caninum) and in the whipworm Trichuris muris, but there was no cross-reaction with human spleen tissue extracts. These results suggest that the nematode-conserved As37 could serve as a ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 2 e0008057 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Leroy Versteeg Junfei Wei Zhuyun Liu Brian Keegan Ricardo T Fujiwara Kathryn M Jones Oluwatoyin Asojo Ulrich Strych Maria Elena Bottazzi Peter J Hotez Bin Zhan Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Ascaris lumbricoides is one of the three major soil-transmitted gastrointestinal helminths (STHs) that infect more than 440 million people in the world, ranking this neglected tropical disease among the most common afflictions of people living in poverty. Children infected with this roundworm suffer from malnutrition, growth stunting as well as cognitive and intellectual deficits. An effective vaccine is urgently needed to complement anthelmintic deworming as a better approach to control helminth infections. As37 is an immunodominant antigen of Ascaris suum, a pig roundworm closely related to the human A. lumbricoides parasite, recognized by protective immune sera from A. suum infected mice. In this study, the immunogenicity and vaccine efficacy of recombinant As37 were evaluated in a mouse model. METHODOLOGY/PRINCIPAL FINDINGS:As37 was cloned and expressed as a soluble recombinant protein (rAs37) in Escherichia coli. The expressed rAs37 was highly recognized by protective immune sera from A. suum egg-infected mice. Balb/c mice immunized with 25 μg rAs37 formulated with AddaVax™ adjuvant showed significant larval worm reduction after challenge with A. suum infective eggs when compared with a PBS (49.7%) or adjuvant control (48.7%). Protection was associated with mixed Th1/2-type immune responses characterized by high titers of serological IgG1 and IgG2a and stimulation of the production of cytokines IL-4, IL-5, IL-10 and IL-13. In this experiment, the AddaVax™ adjuvant induced better protection than the Th1-type adjuvant MPLA (38.9%) and the Th2-type adjuvant Alhydrogel (40.7%). Sequence analysis revealed that As37 is a member of the immunoglobulin superfamily (IgSF) and highly conserved in other human STHs. Anti-As37 antibodies strongly recognized homologs in hookworms (Necator americanus, Ancylostoma ceylanicum, A. caninum) and in the whipworm Trichuris muris, but there was no cross-reaction with human spleen tissue extracts. These results suggest that the nematode-conserved As37 could serve as a ... |
format |
Article in Journal/Newspaper |
author |
Leroy Versteeg Junfei Wei Zhuyun Liu Brian Keegan Ricardo T Fujiwara Kathryn M Jones Oluwatoyin Asojo Ulrich Strych Maria Elena Bottazzi Peter J Hotez Bin Zhan |
author_facet |
Leroy Versteeg Junfei Wei Zhuyun Liu Brian Keegan Ricardo T Fujiwara Kathryn M Jones Oluwatoyin Asojo Ulrich Strych Maria Elena Bottazzi Peter J Hotez Bin Zhan |
author_sort |
Leroy Versteeg |
title |
Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection. |
title_short |
Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection. |
title_full |
Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection. |
title_fullStr |
Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection. |
title_full_unstemmed |
Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection. |
title_sort |
protective immunity elicited by the nematode-conserved as37 recombinant protein against ascaris suum infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008057 https://doaj.org/article/259b44782ea34685a5c28199b05f9587 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 2, p e0008057 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008057 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008057 https://doaj.org/article/259b44782ea34685a5c28199b05f9587 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008057 |
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PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
2 |
container_start_page |
e0008057 |
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1766346337320697856 |