Progress in the development of a recombinant vaccine for human hookworm disease: The Human Hookworm Vaccine Initiative

Authors

Peter J. Hotez, The George Washington UniversityFollow
Bin Zhan, The George Washington University
Jeffrey M. Bethony, The George Washington University
Alex Loukas, The George Washington University
Angela Williamson, The George Washington University
Gaddam Narsa Goud, The George Washington University
John M. Hawdon, The George Washington University
Azra Dobardzic, The George Washington University
Reshad Dobardzic, The George Washington University
Kashinath Ghosh, The George Washington University
Maria Elena Bottazzi, The George Washington University
Susana Mendez, The George Washington University
Bernard Zook, The George Washington University
Yan Wang, The George Washington University
Sen Liu, The George Washington University
Idong Essiet-Gibson, The George Washington University
Sophia Chung-Debose, The George Washington University
Shuhua Xiao, Chinese Center for Disease Control and Prevention
David Knox, Moredun Institute, Edinburgh, UK
Michael Meagher, University of Nebraska - LincolnFollow
Mehmet Inan, University of Nebraska - LincolnFollow
Rodrigo Correa-Oliviera, The George Washington University
Paul Vilk, Sabin Vaccine Institute
Herman R. Shepherd, Sabin Vaccine Institute
Walter Brandt, Sabin Vaccine Institute
Philip K. Russell, Sabin Vaccine Institute

Date of this Version

9-30-2003

Comments

Published in International Journal for Parasitology 33:11 (September 30, 2003), pp. 1245–1258; doi 10.1016/S0020-7519(03)00158-9 Copyright © 2003 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. Used by permission. http://www.parasitology-online.com

Abstract

Hookworm infection is one of the most important parasitic infections of humans, possibly outranked only by malaria as a cause of misery and suffering. An estimated 1.2 billion people are infected with hookworm in areas of rural poverty in the tropics and subtropics. Epidemiological data collected in China, Southeast Asia, and Brazil indicate that, unlike other soil-transmitted helminth infections, the highest hookworm burdens typically occur in adult populations, including the elderly. Emerging data on the host cellular immune responses of chronically infected populations suggest that hookworms induce a state of host anergy and immune hyporesponsiveness. These features account for the high rates of hookworm reinfection following treatment with anthelminthic drugs and therefore, the failure of anthelminthics to control hookworm. Despite the inability of the human host to develop naturally acquired immune responses to hookworm, there is evidence for the feasibility of developing a vaccine based on the successes of immunizing laboratory animals with either attenuated larval vaccines or antigens extracted from the alimentary canal of adult blood-feeding stages. The major antigens associated with each of these larval and adult hookworm vaccines have been cloned and expressed in prokaryotic and eukaryotic systems. However, only eukaryotic expression systems (e.g., yeast, baculovirus, and insect cells) produce recombinant proteins that immunologically resemble the corresponding native antigens. A challenge for vaccinologists is to formulate selected eukaryotic antigens with appropriate adjuvants in order to elicit high antibody titers. In some cases, antigen-specific IgE responses are required to mediate protection. Another challenge will be to produce anti-hookworm vaccine antigens at high yield low cost suitable for immunizing large impoverished populations living in the developing nations of the tropics.