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Infection with parasitic nematodes confounds vaccination efficacy
Authors:Joseph F Urban Jr  Nina R Steenhard  Gloria I Solano-Aguilar  Harry D Dawson  Onyinye I Iweala  Cathryn R Nagler  Gregory S Noland  Nirbhay Kumar  Robert M Anthony  Terez Shea-Donohue  Joel Weinstock  William C Gause
Institution:1. Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, United States;2. Danish Centre for Experimental Parasitology, Department of Veterinary Pathobiology, Copenhagen University, DK-1870 Frederiksberg C, Denmark;3. Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, United States;4. Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, United States;5. Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, United States;6. Mucosal Biology Research Center, University of Maryland-School of Medicine, Baltimore, MD 21201, United States;g Division of Gastroenterology, New England Medical Center, Boston, MA 02111, United States;h Department of Medicine, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, United States
Abstract:T helper (Th) cells produce signature cytokine patterns, induced largely by intracellular versus extracellular pathogens that provide the cellular and molecular basis for counter regulatory expression of protective immunity during concurrent infections. The production of IL-12 and IFN-γ, for example, resulting from exposure to many bacterial, viral, and protozoan pathogens is responsible for Th1-derived protective responses that also can inhibit development of Th2-cells expressing IL-4-dependent immunity to extracellular helminth parasites and vice versa. In a similar manner, concurrent helminth infection alters optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied especially in the context of a challenge infection following vaccination. Demands for new and effective vaccines to control chronic and emerging diseases, and the need for rapid deployment of vaccines for bio security concerns requires a systematic evaluation of confounding factors that limit vaccine efficacy. One common albeit overlooked confounder is the presence of gastrointestinal nematode parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were helminth infections are prevalent, but the interplay between parasites and emerging diseases that can be transmitted worldwide make this a global issue. In addition, it is not clear if the epidemic in allergic disease in industrialized countries substitutes for geohelminth infection to interfere with effective vaccination regimens. This presentation will focus on recent vaccination studies in mice experimentally infected with Heligmosomoides polygyrus to model the condition of gastrointestinal parasite infestation in mammalian populations targeted for vaccination. In addition, a large animal vaccination and challenge model against Mycoplasma hyopneumonia in swine exposed to Ascaris suum will provide a specific example of the need for further work in this area, and for controlled field studies to assess the impact of other similar scenarios.
Keywords:Th2-associated immunity  Immune modulating parasitic infection  Cytokine gene expression  Protective immunity
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