A randomized, placebo-controlled, blinded phase 1 study investigating a novel inactivated, Vero cell-culture derived Zika virus vaccine.

BACKGROUND

Zika virus (ZIKV) is an emerging public health threat, rendering development of a safe and effective vaccine against the virus a high priority to face this unmet medical need. Our vaccine candidate has been developed on the same platform used for the licensed vaccine IXIARO®, a vaccine against Japanese Encephalitis virus, another closely related member of the Flaviviridae family.

METHODS

Between 24 February 2018 and 16 November 2018, we conducted a randomized, observer-blinded, placebo controlled, single center phase 1 study to assess the safety and immunogenicity of an adjuvanted, inactivated, purified whole-virus Zika vaccine candidate in the USA. A total of 67 healthy flavivirus-naïve adults aged 18-49 years were randomly assigned to one of five study arms to receive two immunizations of either high dose or low dose (6 antigen units or 3 antigen units) with both dose levels applied in two different immunization regimens or placebo as control.

RESULTS

Our vaccine candidate showed an excellent safety profile independent of dose and vaccination regimen with predominantly mild adverse events (AEs). No serious AE has been reported. The ZIKV vaccine induced neutralizing antibodies in all tested doses and regimens with seroconversion rates up to 85.7% (high dose), which remained up to 40% (high dose) at 6 months follow-up. Of note, the rapid regimen triggered a substantial immune response within days.

CONCLUSIONS

The rapid development and production of a ZIKV vaccine candidate building on a commercial Vero-cell manufacturing platform resulted in a safe and immunogenic vaccine suitable for further clinical development. To optimize antibody persistence, higher doses and a booster administration might be considered.