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Article

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

1
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
2
Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia
3
School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Ger Rijkers
Vaccines 2021, 9(9), 1034; https://doi.org/10.3390/vaccines9091034
Received: 30 July 2021 / Revised: 14 September 2021 / Accepted: 14 September 2021 / Published: 17 September 2021
(This article belongs to the Special Issue Vaccines Development in Australia)
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, BL10 or LL10, respectively) groups as self-adjuvanting moieties. BL10 and LL10 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 LL10. 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. View Full-Text
Keywords: aspartic protease-1; hookworm; infection challenge; oral vaccine; peptide-based vaccine aspartic protease-1; hookworm; infection challenge; oral vaccine; peptide-based vaccine
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MDPI and ACS Style

Shalash, A.O.; Becker, L.; Yang, J.; Giacomin, P.; Pearson, M.; Hussein, W.M.; Loukas, A.; Skwarczynski, M.; Toth, I. Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy. Vaccines 2021, 9, 1034. https://doi.org/10.3390/vaccines9091034

AMA Style

Shalash AO, Becker L, Yang J, Giacomin P, Pearson M, Hussein WM, Loukas A, Skwarczynski M, Toth I. Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy. Vaccines. 2021; 9(9):1034. https://doi.org/10.3390/vaccines9091034

Chicago/Turabian Style

Shalash, Ahmed O., Luke Becker, Jieru Yang, Paul Giacomin, Mark Pearson, Waleed M. Hussein, Alex Loukas, Mariusz Skwarczynski, and Istvan Toth. 2021. "Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy" Vaccines 9, no. 9: 1034. https://doi.org/10.3390/vaccines9091034

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