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Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy

Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administrat...

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Autores principales: Shalash, Ahmed O., Becker, Luke, Yang, Jieru, Giacomin, Paul, Pearson, Mark, Hussein, Waleed M., Loukas, Alex, Skwarczynski, Mariusz, Toth, Istvan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472562/
https://www.ncbi.nlm.nih.gov/pubmed/34579271
http://dx.doi.org/10.3390/vaccines9091034
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author Shalash, Ahmed O.
Becker, Luke
Yang, Jieru
Giacomin, Paul
Pearson, Mark
Hussein, Waleed M.
Loukas, Alex
Skwarczynski, Mariusz
Toth, Istvan
author_facet Shalash, Ahmed O.
Becker, Luke
Yang, Jieru
Giacomin, Paul
Pearson, Mark
Hussein, Waleed M.
Loukas, Alex
Skwarczynski, Mariusz
Toth, Istvan
author_sort Shalash, Ahmed O.
collection PubMed
description Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administration is a stable and orally administered vaccine. Oral vaccines are advantageous as they negate the need for trained medical staff for administration and do not require strict sterility conditions. Vaccination, therefore, can be carried out at a significantly reduced cost. One of the most promising current antigenic targets for hookworm vaccine development is the aspartic protease digestive enzyme (APR-1). Antibody-mediated neutralization of APR-1 deprives the worm of nourishment, leading to reduced worm burdens in vaccinated hosts. Previously, we demonstrated that, when incorporated into vaccine delivery systems, the APR-1-derived p3 epitope (TSLIAGPKAQVEAIQKYIGAEL) was able to greatly reduce worm burdens (≥90%) in BALB/c mice; however, multiple, large doses of the vaccine were required. Here, we investigated a variety of p3-antigen conjugates to optimize antigen delivery and establish immune response/protective efficacy relationships. We synthesized, purified, and characterized four p3 peptide-based vaccine candidates with: (a) lipidic (lipid core peptide (LCP)); (b) classical polymeric (polymethylacrylate (PMA)); and (c) novel polymeric (polyleucine in a branched or linear arrangement, BL(10) or LL(10), respectively) groups as self-adjuvanting moieties. BL(10) and LL(10) induced the highest serum anti-p3 and anti-APR-1 IgG titers. Upon challenge with rodent hookworms, the highest significant reduction in worm burden was observed in mice immunized with LL(10). APR-1-specific serum IgG titers correlated with worm burden reduction. Thus, we provide the first vaccine-triggered immune response-protection relationship for hookworm infection.
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spelling pubmed-84725622021-09-28 Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy Shalash, Ahmed O. Becker, Luke Yang, Jieru Giacomin, Paul Pearson, Mark Hussein, Waleed M. Loukas, Alex Skwarczynski, Mariusz Toth, Istvan Vaccines (Basel) Article Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administration is a stable and orally administered vaccine. Oral vaccines are advantageous as they negate the need for trained medical staff for administration and do not require strict sterility conditions. Vaccination, therefore, can be carried out at a significantly reduced cost. One of the most promising current antigenic targets for hookworm vaccine development is the aspartic protease digestive enzyme (APR-1). Antibody-mediated neutralization of APR-1 deprives the worm of nourishment, leading to reduced worm burdens in vaccinated hosts. Previously, we demonstrated that, when incorporated into vaccine delivery systems, the APR-1-derived p3 epitope (TSLIAGPKAQVEAIQKYIGAEL) was able to greatly reduce worm burdens (≥90%) in BALB/c mice; however, multiple, large doses of the vaccine were required. Here, we investigated a variety of p3-antigen conjugates to optimize antigen delivery and establish immune response/protective efficacy relationships. We synthesized, purified, and characterized four p3 peptide-based vaccine candidates with: (a) lipidic (lipid core peptide (LCP)); (b) classical polymeric (polymethylacrylate (PMA)); and (c) novel polymeric (polyleucine in a branched or linear arrangement, BL(10) or LL(10), respectively) groups as self-adjuvanting moieties. BL(10) and LL(10) induced the highest serum anti-p3 and anti-APR-1 IgG titers. Upon challenge with rodent hookworms, the highest significant reduction in worm burden was observed in mice immunized with LL(10). APR-1-specific serum IgG titers correlated with worm burden reduction. Thus, we provide the first vaccine-triggered immune response-protection relationship for hookworm infection. MDPI 2021-09-17 /pmc/articles/PMC8472562/ /pubmed/34579271 http://dx.doi.org/10.3390/vaccines9091034 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shalash, Ahmed O.
Becker, Luke
Yang, Jieru
Giacomin, Paul
Pearson, Mark
Hussein, Waleed M.
Loukas, Alex
Skwarczynski, Mariusz
Toth, Istvan
Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy
title Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy
title_full Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy
title_fullStr Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy
title_full_unstemmed Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy
title_short Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy
title_sort oral peptide vaccine against hookworm infection: correlation of antibody titers with protective efficacy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472562/
https://www.ncbi.nlm.nih.gov/pubmed/34579271
http://dx.doi.org/10.3390/vaccines9091034
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