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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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/9/1034 |
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| author | Ahmed O. Shalash Luke Becker Jieru Yang Paul Giacomin Mark Pearson Waleed M. Hussein Alex Loukas Mariusz Skwarczynski Istvan Toth |
| author_facet | Ahmed O. Shalash Luke Becker Jieru Yang Paul Giacomin Mark Pearson Waleed M. Hussein Alex Loukas Mariusz Skwarczynski Istvan Toth |
| author_sort | Ahmed O. Shalash |
| collection | DOAJ |
| 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<sub>10</sub> or LL<sub>10</sub>, respectively) groups as self-adjuvanting moieties. BL<sub>10</sub> and LL<sub>10</sub> 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<sub>10</sub>. 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. |
| first_indexed | 2024-03-10T07:08:41Z |
| format | Article |
| id | doaj.art-6a6f34049d214de9a7621268816c1cbe |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T07:08:41Z |
| publishDate | 2021-09-01 |
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| series | Vaccines |
| spelling | doaj.art-6a6f34049d214de9a7621268816c1cbe2023-11-22T15:35:09ZengMDPI AGVaccines2076-393X2021-09-0199103410.3390/vaccines9091034Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective EfficacyAhmed O. Shalash0Luke Becker1Jieru Yang2Paul Giacomin3Mark Pearson4Waleed M. Hussein5Alex Loukas6Mariusz Skwarczynski7Istvan Toth8School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, AustraliaSchool of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, AustraliaSchool of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, AustraliaSchool of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, AustraliaSchool of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, AustraliaApproximately 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<sub>10</sub> or LL<sub>10</sub>, respectively) groups as self-adjuvanting moieties. BL<sub>10</sub> and LL<sub>10</sub> 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<sub>10</sub>. 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.https://www.mdpi.com/2076-393X/9/9/1034aspartic protease-1hookworminfection challengeoral vaccinepeptide-based vaccine |
| spellingShingle | Ahmed O. Shalash Luke Becker Jieru Yang Paul Giacomin Mark Pearson Waleed M. Hussein Alex Loukas Mariusz Skwarczynski Istvan Toth Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy Vaccines aspartic protease-1 hookworm infection challenge oral vaccine peptide-based vaccine |
| 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 | aspartic protease-1 hookworm infection challenge oral vaccine peptide-based vaccine |
| url | https://www.mdpi.com/2076-393X/9/9/1034 |
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