Peptide-Based Subunit Vaccine against Hookworm Infection

Skwarczynski, Mariusz, Dougall, Annette M., Khoshnejad, Makan, Chandrudu, Saranya, Pearson, Mark S., Loukas, Alex and Toth, Istvan (2012) Peptide-Based Subunit Vaccine against Hookworm Infection. PLoS One, 7 10 Article #e46870: . doi:10.1371/journal.pone.0046870

Author Skwarczynski, Mariusz
Dougall, Annette M.
Khoshnejad, Makan
Chandrudu, Saranya
Pearson, Mark S.
Loukas, Alex
Toth, Istvan
Title Peptide-Based Subunit Vaccine against Hookworm Infection
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-10-03
Sub-type Article (original research)
DOI 10.1371/journal.pone.0046870
Open Access Status DOI
Volume 7
Issue 10 Article #e46870
Total pages 7
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2013
Language eng
Formatted abstract
Hookworms infect more people than HIV and malaria combined, predominantly in third world countries. Treatment of infection with chemotherapy can have limited efficacy and re-infections after treatment are common. Heavy infection often leads to debilitating diseases. All these factors suggest an urgent need for development of vaccine. In an attempt to develop a vaccine targeting the major human hookworm, Necator americanus, a B-cell peptide epitope was chosen from the apical enzyme in the hemoglobin digestion cascade, the aspartic protease Na-APR-1. The A(291)Y alpha helical epitope is known to induce neutralizing antibodies that inhibit the enzymatic activity of Na-APR-1, thus reducing the capacity for hookworms to digest hemoglobin and obtain nutrients. A(291)Y was engineered such that it was flanked on both termini by a coil-promoting sequence to maintain native conformation, and subsequently incorporated into a Lipid Core Peptide (LCP) self-adjuvanting system. While A(291)Y alone or the chimeric epitope with or without Freund's adjuvants induced negligible IgG responses, the LCP construct incorporating the chimeric peptide induced a strong IgG response in mice. Antibodies produced were able to bind to and completely inhibit the enzymatic activity of Na-APR-1. The results presented show that the new chimeric LCP construct can induce effective enzyme-neutralising antibodies in mice, without the help of any additional toxic adjuvants. This approach offers promise for the development of vaccines against helminth parasites of humans and their livestock and companion animals.
Keyword Hookworm Infections
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes epub ahead of print

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 19 Oct 2012, 09:36:33 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences