Photo from NIAID
Investigator pipets samples at the NIAID Vaccine Research Center
An experimental Zika vaccine is safe and induces an immune response in healthy adults, according to research published in The Lancet.
Investigators tested 2 potential Zika vaccines, VRC5288 and VRC5283, in a pair of phase 1 trials.
Both vaccines were considered well-tolerated, but one of them, VRC5283, induced a greater immune response than the other.
Both vaccines were developed by investigators at the National Institute of Allergy and Infectious Diseases (NIAID).
Now, NIAID is leading an international effort to evaluate VRC5283 in a phase 2/2b trial.
“Following early reports that Zika infection during pregnancy can lead to birth defects, NIAID scientists rapidly created one of the first investigational Zika vaccines using a DNA-based platform and began initial studies in healthy adults less than 1 year later,” said NIAID Director Anthony S. Fauci, MD.
To create their vaccines, the investigators inserted into plasmids genes that encode proteins found on the surface of the Zika virus.
The team developed 2 different plasmids for clinical testing: VRC5288 (Zika virus and Japanese encephalitis virus chimera) and VRC5283 (wild-type Zika virus).
In August 2016, NIAID initiated a phase 1 trial of the VRC5288 plasmid in 80 healthy volunteers ages 18 to 35. Subjects received a 4 mg dose via a needle and syringe injection in the arm muscle.
They received doses of VRC5288 at 0 and 8 weeks; 0 and 12 weeks; 0, 4, and 8 weeks; or 0, 4, and 20 weeks.
In December 2016, NIAID initiated a separate trial testing the VRC5283 plasmid. This study enrolled 45 healthy volunteers ages 18 to 50.
Subjects in this trial received 4 mg doses of VRC5283 at 0, 4, and 8 weeks. They were vaccinated in 3 different ways—via single-dose needle and syringe injection in 1 arm, via split-dose needle and syringe injection in each arm, or via needle-free injection in each arm.
Safety
The vaccinations were considered safe and well-tolerated in both trials, although some participants experienced mild to moderate reactions.
Local reactions (with VRC5288 and VRC5283, respectively) included pain/tenderness (mild—46% and 73%, moderate—0% and 7%), mild swelling (1% and 7%), and mild redness (6% and 2%).
Systemic reactions (with VRC5288 and VRC5283, respectively) included malaise (mild—25% and 33%, moderate—3% and 4%), myalgia (mild—18% and 13%, moderate—4% and 7%), headache (mild—19% and 29%, moderate—4% and 4%), chills (mild—6% and 2%, moderate—1% and 2%), nausea (mild—8% and 4%, moderate—1% and 0%), and joint pain (mild—5% and 16%, moderate—0% and 2%).
Immunogenicity
The investigators analyzed blood samples from all subjects 4 weeks after their final vaccinations.
The team found that 60% to 89% of subjects generated a neutralizing antibody response to VRC5288, and 77% to 100% of subjects generated a neutralizing antibody response to VRC5283.
Subjects who received VRC5283 via the needle-free injector all generated a neutralizing antibody response and had the highest levels of neutralizing antibodies.
Subjects who received VRC5283 in a split-dose administered to both arms had more robust immune responses than those receiving the full dose in 1 arm.
“NIAID has begun phase 2 testing of this candidate to determine if it can prevent Zika virus infection, and the promising phase 1 data . . . support its continued development,” Dr Fauci said.
