© 2008 The Authors 293 Journal compilation © 2008 Blackwell Publishing Ltd Parasite Immunology , 2008, 30, 293–303 DOI: 10.1111/j.1365-3024.2008.01023.x Blackwell Publishing Ltd ORIGINAL ARTICLES Mucosal antibodies in hookworm infection Mucosal antibody responses in experimental hookworm infection R. D. BUNGIRO JR, 1 T. SUN, 1 L. M. HARRISON, 1 C. B. SHOEMAKER 2 & M. CAPPELLO 1 1 Program in International Child Health, Departments of Pediatrics and Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA, 2 Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA SUMMARY Hookworms are bloodfeeding nematodes that reside in the intestinal mucosa. These parasites secrete proteins that induce robust systemic immune responses in humans and experimental animals. By contrast, mucosal immune responses in and around the site of attachment are not described as well. This paper presents data from studies aimed at examining hookworm- specific mucosal antibody responses in a hamster model of Ancylostoma ceylanicum infection. Intestinal flush prepared from infected hamsters was analysed by ELISA and shown to be enriched in IgA-specific for A. ceylanicum excretory– secretory (ES) products. Evaluation of mucosal IgA responses by immunoblot demonstrated that infected hamsters recognized a broad range of ES proteins. Hamsters repeatedly exposed to drug-terminated infections were shown to have enhanced serum IgG and mucosal IgA responses, as well as a high level of protection from challenge infection. Parasite-specific IgA was also detected in the faeces of hamsters undergoing a primary infection, and increasing faecal IgA responses were coincident with significant reductions in intestinal worm burdens and faecal ES output over time. Together these results suggest that secretory IgA may act in concert with other components of the mucosal and systemic immune response to promote protective immunity against hookworm infection and/ or disease. Keywords Ancylostoma ceylanicum, hamster, hookworm, IgA, mucosal immunity INTRODUCTION Hundreds of millions of persons worldwide continue to harbour hookworm infections (1). These bloodfeeding soil transmitted nematodes are a major cause of anaemia and malnutrition, and as such rank among the foremost agents of global morbidity (2), especially among children and women of childbearing age (3–6). It has been suggested that the immunomodulatory influence of hookworms and other helminth infections may exacerbate the clinical course of globally significant infectious diseases such as tuberculosis and HIV-AIDS, and also reduce the efficacy of vaccines (7–10). Although effective anthelminthic agents for hookworm are available, rapid reinfection (11,12), and the possibility of emerging drug resistance (13), suggest that existing control methods may become less effective in the future. Consequently new strategies to control hookworm disease, such as vaccines (14) and novel therapeutics (15) are needed to augment currently available control options. Such efforts will be aided by a thorough understanding of host immune response pheno- types that are germane to protection and susceptibility. The immune response to hookworms has been the subject of numerous studies in both humans and animals (as reviewed in Refs (16–18)), with considerable attention focusing on the Syrian golden hamster (Mesocricetus auratus) model of Ancylostoma ceylanicum infection. In contrast to mice, which do not permit the development of Ancylostoma spp. hook- worms upon larval infection (19,20) and do not support extended parasite survival following adoptive transfer of adult worms (21), immunocompetent hamsters are fully permissive hosts for A. ceylanicum (22,23). Furthermore, when infected with a sublethal dose of A. ceylanicum larvae, weanling hamsters exhibit the delayed growth and anaemia which typify human disease (24–26). These findings, coupled with the inherent advantages of rodent models as compared to larger species, have made the hamster model of A. ceylanicum infection ideal for studies of hookworm pathogenesis and vaccine development (24,27–36). A limitation of the hamster model, however, has been the relative paucity of commercially available immunological reagents, which has hampered the detailed study of immune responses in this species (16). Correspondence: Richard D. Bungiro Jr., Yale Child Health Research Center, 464 Congress Avenue, New Haven, CT 06520, USA (e-mail: richard.bungiro@yale.edu). Received: 29 October 2007 Accepted for publication: 4 February 2008