Date: 2016-11-10
Type of
information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Vaccines
Company: Inovio Pharmaceuticals (USA - PA)
Product: GLS-5700
Action
mechanism: DNA vaccine. GLS-5700 is a synthetic DNA plasmid vaccine against the Zika virus.This Zika vaccine was developed in a collaboration between Inovio Pharmaceuticals, The Wistar Institute, and GeneOne Life Science.
Disease: Zika virus infection
Therapeutic
area: Infectious diseases
Country:
Trial
details:
Latest
news:
- • On June 7, 2017, Inovio Pharmaceuticals announced its DNA-based Zika vaccine (GLS-5700) protected against Zika virus-induced damage to testes and sperm, and prevented persistence of the virus in the reproductive tract of all vaccinated male mice challenged with a high dose of the Zika virus. This preclinical study data was published in Nature Communications in an article entitled, “DNA Vaccination Protects Mice Against Zika Virus-Induced Damage to the Testes,” written by Inovio scientists and collaborators.
- Results from a previous preclinical study with GLS-5700 were published in Nature Partner Journals (npj) Vaccines and demonstrated that a single dose of Inovio’s Zika vaccine protected 100% of mice from infection, brain damage and death after exposure to the virus (see below).
- In the first-ever human study of a Zika vaccine, Inovio reported that in its phase I study (ZIKA-001), after a three dose vaccine regimen with GLS-5700 high levels of binding antibodies were measured (ELISA) in 100% (39 of 39) of evaluated subjects. Moreover, two doses or a single dose of vaccine generated a robust antibody response in 95% (37 of 39) and 40% (16 of 40) of evaluated subjects, respectively. Inovio’s second phase I study of 160 subjects in Puerto Rico (ZIKA-002) will complete enrollment this month. In this randomized, placebo-controlled, double-blind trial, 80 subjects received vaccine and 80 subjects received placebo. The study is evaluating the safety, tolerability and immunogenicity of GLS-5700 and assessing differences in Zika infection rates between the arms as an exploratory signal of vaccine efficacy. Inovio is now planning for a larger phase 2 study.
- • On November 10, 2016, Inovio Pharmaceuticals announced the publication of results in Nature Partner Journals (npj) Vaccines demonstrating that its Zika DNA vaccine (GLS-5700) protected animals from infection, brain damage and death. In this study 100% of GLS-5700 vaccinated animals were protected from Zika infection after exposure to the virus. In addition, vaccinated mice were protected from degeneration in the cerebral cortex and hippocampal areas of the brain while unvaccinated mice showed significant degeneration of the brain after Zika infection.
- Prior preclinical studies have tested potential Zika vaccine candidates in animal models involving normal mice and non-human primates that are naturally resistant to Zika. While providing useful immunology data, they cannot provide relevant evidence of an effective means of controlling the spread or medical impacts of this disease by vaccination. In addition to reporting immunogenicity in such Zika-resistant species, this paper represents the first published research to also analyze a Zika vaccine using the special transgenic murine strain A129 lacking interferon alpha and beta receptors (IFNAR-/-), making them highly susceptible to Zika infection and disease. Taking this extra step provided data on how vaccine-generated immune responses could protect against a lethal viral challenge and demonstrates the benefit a Zika vaccine might provide in people.
- This study demonstrated that Inovio’s synthetic DNA vaccine expressed antigens specific to Zika and generated robust antigen-specific and neutralizing antibody and T cell responses in mouse and non-human primate models. Moreover, the study also demonstrated that GLS-5700 provided protection against the disease and death in Zika-susceptible A129 transgenic mice while also being neuroprotective, meaning the disease was unable to spread to the brain. This is especially important given the risk that babies born with the disease have of developing microcephaly, a birth defect resulting in an abnormally small head and that may prevent the brain from developing properly.
- This Zika vaccine is currently in two human clinical studies. Inovio expects to report phase I data before the end of this year from the first 40-subject study being conducted in Miami, Philadelphia and Quebec City. In August, the companies initiated a second study of GLS-5700 in 160 subjects in Puerto Rico. The CDC estimates that Zika will infect more than 25 percent of the Puerto Rican population by the end of the year, providing the potential for this study’s placebo control design to provide exploratory signals of vaccine efficacy in 2017.
Is
general: Yes
