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https://www.arca.fiocruz.br/handle/icict/26484
SAFETY AND IMMUNOGENICITY OF THE NA-GST-1 HOOKWORM VACCINE IN BRAZILIAN AND AMERICAN ADULTS
Antibodies
Hookworms
Enzyme-linked immunoassays
Hepatitis B
Recombinant vaccines
Author
Diemert, David J.
Freire, Janaína de Moura
Valente, Vanderson Firmiano
Fraga, Carlos Geraldo
Talles, Frederico
Grahek, Shannon
Campbell, Doreen
Jariwala, Amar
Periago, Maria Victoria
Enk, Martin Johannes
Bethony, Maria Flávia Gazzinelli
Bottazzi, Maria Elena
Hamilton, Robert
Brelsford, Jill
Yakovleva, Anna
Li, Guangzhao
Peng, Jin
Oliveira, Rodrigo Correa de
Hotez, Peter Jay
Bethony, Jeffrey Michael
Freire, Janaína de Moura
Valente, Vanderson Firmiano
Fraga, Carlos Geraldo
Talles, Frederico
Grahek, Shannon
Campbell, Doreen
Jariwala, Amar
Periago, Maria Victoria
Enk, Martin Johannes
Bethony, Maria Flávia Gazzinelli
Bottazzi, Maria Elena
Hamilton, Robert
Brelsford, Jill
Yakovleva, Anna
Li, Guangzhao
Peng, Jin
Oliveira, Rodrigo Correa de
Hotez, Peter Jay
Bethony, Jeffrey Michael
Affilliation
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Faculdade Enfermagem. Belo Horizonte, MG, Brasil.
Department of Pediatrics. Section of Pediatric Tropical Medicine. Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development. National School of Tropical Medicine. Baylor College of Medicine. Houston, TX, USA.
Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Department of Pediatrics. Section of Pediatric Tropical Medicine. Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development. National School of Tropical Medicine. Baylor College of Medicine. Houston, TX, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Faculdade Enfermagem. Belo Horizonte, MG, Brasil.
Department of Pediatrics. Section of Pediatric Tropical Medicine. Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development. National School of Tropical Medicine. Baylor College of Medicine. Houston, TX, USA.
Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Department of Pediatrics. Section of Pediatric Tropical Medicine. Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development. National School of Tropical Medicine. Baylor College of Medicine. Houston, TX, USA.
Department of Microbiology, Immunology and Tropical Medicine. School of Medicine and Health Sciences. The George Washington University. Washington DC, USA.
Abstract
Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) plays a role in the digestion of host hemoglobin by adult N. americanus hookworms. Vaccination of laboratory animals with recombinant Na-GST-1 is associated with significant protection from challenge infection. Recombinant Na-GST-1 was expressed in Pichia pastoris and adsorbed to aluminum hydroxide adjuvant (Alhydrogel) according to current Good Manufacturing Practice. Two Phase 1 trials were conducted in 142 healthy adult volunteers in the United States and Brazil, first in hookworm-naïve individuals and then in residents of a N. americanus endemic area in Brazil. Volunteers received one of three doses of recombinant Na-GST-1 (10, 30, or 100 μg) adjuvanted with Alhydrogel, adjuvanted with Alhydrogel and co-administered with an aqueous formulation of Glucopyranosyl Lipid A (GLA-AF), or the hepatitis B vaccine. Vaccinations were administered via intramuscular injection on days 0, 56, and 112. Na-GST-1/Alhydrogel was well tolerated in both hookworm-naïve and hookworm-exposed adults, with the most common adverse events being mild to moderate injection site pain and tenderness, and mild headache and nausea; no vaccine-related severe or serious adverse events were observed. Antigen-specific IgG antibodies were induced in a dose-dependent fashion, with increasing levels observed after each vaccination in both trials. The addition of GLA-AF to Na-GST-1/Alhydrogel did not result in significant increases in specific IgG responses. In both the US and Brazil studies, the predominant IgG subclass induced against Na-GST-1 was IgG1, with lesser amounts of IgG3. Vaccination of both hookworm-naïve and hookworm-exposed adults with recombinant Na-GST-1 was safe, well tolerated, and resulted in significant antigen-specific IgG responses. Based on these results, this vaccine will be advanced into clinical trials in children and eventual efficacy studies.
Keywords
Vaccination and immunizationAntibodies
Hookworms
Enzyme-linked immunoassays
Hepatitis B
Recombinant vaccines
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