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, and Toth, Istvan (2021) Oral peptide vaccine against hookworm infection: correlation of antibody titers with protective efficacy. Vaccines, 9. 1034.

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Abstract

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.

Item ID: 70127
Item Type: Article (Research - C1)
ISSN: 2076-393X
Keywords: Aspartic protease-1, Hookworm, Infection challenge, Oral vaccine, Peptide-based vaccine
Copyright Information: © 2021 by the authors. 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/).
Funders: Australian Research Council (ARC), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: ARC DP21010280, NHMRC program grant APP1132975, NHMRC 1117504
Date Deposited: 19 Nov 2021 01:52
FoR Codes: 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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