Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults

• Autores: Diemert, David J.; Freire, Janaína; Vanderson, Valente; Talles, Federico; Grahek, Shannon; Campbell, Doreen; Jariwala, Amar; Periago, Maria Victoria; Enk, Martin; Gazzinelli, María Flavia; Bottazzi, María Elena; Hamilton, Roberto; Brelsford, Jill; Yakovleva, Anna; Guangzhao, Li; Peng, Jin; Correa Oliveira, Rodrigo; Hotez, Peter; Bethony, Jeffrey
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: HOOKWORM; NECATOR AMERICANUS; VACCINE; BRAZIL
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Diemert, David J.. The George Washington University; Estados Unidos
Fil: Freire, Janaína. Fundación Oswaldo Cruz; Brasil
Fil: Vanderson, Valente. Fundación Oswaldo Cruz; Brasil
Fil: Talles, Federico. Fundación Oswaldo Cruz; Brasil
Fil: Grahek, Shannon. The George Washington University; Estados Unidos
Fil: Campbell, Doreen. The George Washington University; Estados Unidos
Fil: Jariwala, Amar. The George Washington University; Estados Unidos
Fil: Periago, Maria Victoria. Fundación Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Enk, Martin. Fundación Oswaldo Cruz; Brasil
Fil: Gazzinelli, María Flavia. Universidade Federal do Minas Gerais; Brasil
Fil: Bottazzi, María Elena. Baylor College of Medicine; Estados Unidos
Fil: Hamilton, Roberto. University Johns Hopkins; Estados Unidos
Fil: Brelsford, Jill. The George Washington University; Estados Unidos
Fil: Yakovleva, Anna. The George Washington University; Estados Unidos
Fil: Guangzhao, Li. The George Washington University; Estados Unidos
Fil: Peng, Jin. The George Washington University; Estados Unidos
Fil: Correa Oliveira, Rodrigo. Fundación Oswaldo Cruz; Brasil
Fil: Hotez, Peter. Baylor College of Medicine; Estados Unidos
Fil: Bethony, Jeffrey. The George Washington University; Estados Unidos