We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults.
- Authors
Diemert, David J.; Freire, Janaína; Valente, Vanderson; Fraga, Carlos Geraldo; Talles, Frederico; Grahek, Shannon; Campbell, Doreen; Jariwala, Amar; Periago, Maria Victoria; Enk, Martin; Gazzinelli, Maria Flávia; Bottazzi, Maria Elena; Hamilton, Robert; Brelsford, Jill; Yakovleva, Anna; Li, Guangzhao; Peng, Jin; Correa-Oliveira, Rodrigo; Hotez, Peter; Bethony, Jeffrey
- 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. Trial registration: ClinicalTrials.gov ( for the Brazil trial and for the US trial)
- Subjects
HOOKWORM disease; NECATOR americanus; GLUTATHIONE transferase; PICHIA pastoris; ALUMINUM hydroxide; VACCINATION
- Publication
PLoS Neglected Tropical Diseases, 2017, Vol 11, Issue 5, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0005574