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

PLoS Negl Trop Dis. 2017 May 2;11(5):e0005574. doi: 10.1371/journal.pntd.0005574. eCollection 2017 May.


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: (NCT01261130 for the Brazil trial and NCT01385189 for the US trial).

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adolescent
  • Adult
  • Aluminum Hydroxide / administration & dosage
  • Ancylostomatoidea / immunology*
  • Animals
  • Antibodies, Helminth / blood
  • Antigens, Helminth / immunology*
  • Brazil
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Glucosides / administration & dosage
  • Glutathione Transferase / immunology*
  • Healthy Volunteers
  • Hepatitis B Vaccines / administration & dosage
  • Hookworm Infections / immunology
  • Hookworm Infections / prevention & control*
  • Humans
  • Immunoglobulin G / blood
  • Injections, Intramuscular
  • Lipid A / administration & dosage
  • Male
  • Middle Aged
  • Treatment Outcome
  • United States
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology*
  • Young Adult


  • Adjuvants, Immunologic
  • Antibodies, Helminth
  • Antigens, Helminth
  • Glucosides
  • Hepatitis B Vaccines
  • Immunoglobulin G
  • Lipid A
  • Vaccines, Synthetic
  • glucopyranosyl lipid-A
  • Aluminum Hydroxide
  • Glutathione Transferase

Associated data


Grant support

The investigators received financial support from the Albert B. Sabin Vaccine Institute (ABSVI), which was involved in all aspects of study design and interpretation. ABSVI funded this work through grants from the Bill & Melinda Gates Foundation and the Ministry of Foreign Affairs of the Government of the Netherlands. In addition, the trial conducted in Washington, DC, was partially supported by the GW-CNMC Clinical and Translational Science Institute through Award Number UL1RR031988 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. The funders had no role in data collection and analysis, decision to publish, or preparation of the manuscript.