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

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. © 2017 diemert et al.