Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: Implications for the development of vaccines against helminths David J. Diemert, MD,

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Presentation transcript:

Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: Implications for the development of vaccines against helminths David J. Diemert, MD, FRCP(C), Antonio G. Pinto, MD, Janaina Freire, MD, Amar Jariwala, MD, Helton Santiago, MD, PhD, Robert G. Hamilton, PhD, Maria Victoria Periago, PhD, Alex Loukas, PhD, Leon Tribolet, BSc, Jason Mulvenna, PhD, Rodrigo Correa-Oliveira, PhD, Peter J. Hotez, MD, PhD, Jeffrey M. Bethony, PhD Journal of Allergy and Clinical Immunology Volume 130, Issue 1, Pages 169-176.e6 (July 2012) DOI: 10.1016/j.jaci.2012.04.027 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Levels of IgE against Na-ASP-2 (A) and total IgE (B) in participants before immunization with Na-ASP-2/Alhydrogel, as measured by using ImmunoCAP. HBV, Subjects who received hepatitis B vaccine; LOD, limit of detection; Non-Urticaria, subjects who did not have generalized urticaria after vaccination with Na-ASP-2; Urticaria, subjects who had generalized urticaria after a single vaccination (10 μg) with the Na-ASP-2 vaccine. Journal of Allergy and Clinical Immunology 2012 130, 169-176.e6DOI: (10.1016/j.jaci.2012.04.027) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Anti–Na-ASP-2 IgG levels by study day, as measured by using ImmunoCAP. Data are arithmetic mean antibody levels, with bars showing SEs. Solid circles represent subjects who had a generalized urticarial response after a single vaccination (10 μg) with the Na-ASP-2 vaccine. Open circles represent subjects who did not have generalized urticaria after a single vaccination with Na-ASP-2/Alhydrogel. Gray boxes represent subjects who received hepatitis B vaccine. Journal of Allergy and Clinical Immunology 2012 130, 169-176.e6DOI: (10.1016/j.jaci.2012.04.027) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Levels of Na-ASP-2–specific IgE by age and study. Data are from 3 studies of adults and children between 1 and 85 years of age residing in hookworm-endemic areas in and around Americaninhas (site of the phase I trial), Minas Gerais state, Brazil. Serum samples were collected from both hookworm-positive and hookworm-negative subjects and reflect IgE levels to Na-ASP-2 before treatment of soil-transmitted helminth infections with albendazole. Also presented are data for the 9 volunteers in the phase I study of the Na-ASP-2 hookworm vaccine in healthy Brazilian adults previously infected with N americanus, as well as a phase I study of the vaccine conducted in healthy American hookworm–naive adults.12 IgE to Na-ASP-2 is expressed in arbitrary units of antibody, as determined by using a qualified indirect ELISA. Journal of Allergy and Clinical Immunology 2012 130, 169-176.e6DOI: (10.1016/j.jaci.2012.04.027) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 A 3-dimensional representation of Na-ASP-2 based on its crystalline structure highlighting the epitopes that are uniquely or jointly recognized by IgG and IgE antibodies, as determined by using sera collected from the 9 participants in the phase I trial of Na-ASP-2 in Brazilian adults. Epitopes in blue are those recognized by IgG, those in red are recognized by IgE, and those in purple are recognized by both IgG and IgE. Journal of Allergy and Clinical Immunology 2012 130, 169-176.e6DOI: (10.1016/j.jaci.2012.04.027) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Levels of IgE to Na-ASP-2 (A) and total IgE levels (B) by study day, as measured by using ImmunoCAP. Solid circles represent subjects who had generalized urticaria after a single vaccination (10 μg) with the Na-ASP-2 vaccine. Open circles represent subjects who did not have generalized urticaria after vaccination with Na-ASP-2. Gray boxes represent subjects who received hepatitis B vaccine. Journal of Allergy and Clinical Immunology 2012 130, 169-176.e6DOI: (10.1016/j.jaci.2012.04.027) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Relationship between levels of IgE to Na-ASP-2 (expressed in arbitrary units) and age in years for subjects living in and around the phase I study site of Americaninhas before treatment with albendazole. Journal of Allergy and Clinical Immunology 2012 130, 169-176.e6DOI: (10.1016/j.jaci.2012.04.027) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Relationship between levels of IgE to Na-ASP-2 (expressed in arbitrary units) and the intensity of N americanus infection (expressed as eggs per gram of feces) for subjects residing in and around the phase I study site of Americaninhas before treatment with albendazole. Journal of Allergy and Clinical Immunology 2012 130, 169-176.e6DOI: (10.1016/j.jaci.2012.04.027) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions