Two DNA vaccines were safe and well tolerated by participants in a phase 1 trial, according to research published in The Lancet, with one vaccine being advanced to phase 2 study.
The recent outbreak of Zika virus in the Americas and its associated complications, such as microcephaly, has prompted numerous trials into potential vaccine candidates. The Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), in Bethesda, Maryland, developed 2 DNA vaccine candidates against Zika: plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera) and plasmid VRC5283 (wild-type Zika virus).
Two phase 1, randomized, open-label trials testing different vaccine schedules and delivery methods were completed (ClinicalTrials.gov: NCT02840487 and NCT02996461). VRC 319 enrolled 80 patients (20 in each group) and tested VRC5288 administered by needle and syringe at 0 and 8 weeks; 0 and 12 weeks; 0, 4, and 8 weeks; and 0, 4, and 20 weeks. VRC 320 enrolled 45 participants (15 in each group) to receive VRC5283 at 0, 4, and 8 weeks via single-dose needle and syringe injection, split-dose needle and syringe, or split-dose needle-free injection with the Stratis® device (PharmaJet).
Both vaccines were safe, well tolerated, and immunogenic, but the greatest effects were seen in the split-dose needle-free VRC5283 group. This group had the highest detectable antibody responses with neutralizing antibody and T-cell responses of the greatest magnitude seen in 100% of group participants. The needle-free delivery and split-dose schedule also achieved the greatest geometric mean titres of antibodies.
Local and systemic symptoms reported in both trials were all mild to moderate. Pain and tenderness was the most common local symptom (46% of participants in VRC 319 and 80% in VRC 320), and malaise and headache were the most common systemic symptoms (27% and 22%, respectively, in VRC 319 and 38% and 33%, respectively, in VRC 320).
VRC5283 has been advanced to an international phase 2 efficacy trial, and several other vaccine approaches are being pursued in joint efforts to curb the spread of the Zika virus.
Gaudinski MR, Houser KV, Morabito KM, et al; and the VRC 319 and VRC 320 study teams. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials [published online December 4, 2017]. Lancet. doi: 10.1016/S0140-6736(17)33105-7