Details

Autor(en) / Beteiligte

• Diemert, David J., MD, FRCP(C)
• Pinto, Antonio G., MD
• Freire, Janaina, MD
• Jariwala, Amar, MD
• Santiago, Helton, MD, PhD
• Hamilton, Robert G., PhD
• Periago, Maria Victoria, PhD
• Loukas, Alex, PhD
• Tribolet, Leon, BSc
• Mulvenna, Jason, PhD
• Correa-Oliveira, Rodrigo, PhD
• Hotez, Peter J., MD, PhD
• Bethony, Jeffrey M., PhD

Titel

Generalized urticaria induced by the Na -ASP-2 hookworm vaccine: Implications for the development of vaccines against helminths

Ist Teil von

• Journal of allergy and clinical immunology, 2012-07, Vol.130 (1), p.169-176.e6

Ort / Verlag

New York, NY: Mosby, Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Background Necator americanus Ancylostoma-secreted protein 2 ( Na -ASP-2) is secreted by infective hookworm larvae on entry into human hosts. Vaccination of laboratory animals with recombinant Na -ASP-2 provides significant protection against challenge infections. In endemic areas antibodies to Na -ASP-2 are associated with reduced risk of heavy N americanus infections. Objective To assess the safety and immunogenicity of recombinant Na -ASP-2 adjuvanted with Alhydrogel in healthy Brazilian adults previously infected with N americanus. Methods Participants were randomized to receive Na -ASP-2 or hepatitis B vaccine. Major IgG and IgE epitopes of the Na -ASP-2 molecule were mapped by using sera from these same subjects. Seroepidemiologic studies in adults and children residing in hookworm-endemic areas were conducted to assess the prevalence of IgE responses to Na -ASP-2. Results Vaccination with a single dose of Na -ASP-2 resulted in generalized urticarial reactions in several volunteers. These reactions were associated with pre-existing Na -ASP-2–specific IgE likely induced by previous hookworm infection. Surveys revealed that a significant proportion of the population in hookworm-endemic areas had increased levels of IgE to Na -ASP-2. Epitope mapping demonstrated sites on the Na -ASP-2 molecule that are uniquely or jointly recognized by IgG and IgE antibodies. Conclusion Infection with N americanus induces increased levels of total and specific IgE to Na -ASP-2 that result in generalized urticaria on vaccination with recombinant Na -ASP-2. These data advance knowledge of vaccine development for helminths given their propensity to induce strong TH 2 responses. Study data highlight the important differences between the immune responses to natural helminth infection and to vaccination with a recombinant helminth antigen.