Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial

Abstract

Background The development of an effective vaccine against Zika virus remains a public health priority. A Zika purified inactivated virus (ZPIV) vaccine candidate has been shown to protect animals against Zika virus challenge and to be well tolerated and immunogenic in humans up to 8 weeks of follow-up. We aimed to assess the safety and immunogenicity of ZPIV in humans up to 52 weeks of follow-up when given via standard or accelerated vaccination schedules. MethodsWe did a single-centre, double-blind, randomised controlled, phase 1 trial in healthy adults aged 18-50 years with no known history of flavivirus vaccination or infection at Beth Israel Deaconess Medical Center in Boston, MA, USA. Participants were sequentially enrolled into one of three groups: ZPIV given at weeks 0 and 4 (standard regimen), weeks 0 and 2 (accelerated regimen), or week 0 alone (single-dose regimen). Within each group, participants were randomly assigned using a computer-generated randomisation schedule to receive an intramuscular injection of 5 μg ZPIV or saline placebo, in a ratio of 5:1. The sponsor, clinical staff, investigators, participants, and laboratory personnel were masked to treatment assignment. The primary endpoint was safety up to day 364 after final dose administration, and secondary endpoints were proportion of participants with positive humoral immune responses (50% microneutralisation titre [MN 50 ] ≥100) and geometric mean MN 50 at observed peak response (ie, the highest neutralising antibody level observed for an individual participant across all timepoints) and week 28. All participants who received at least one dose of ZPIV or placebo were included in the safety population; the analysis of immunogenicity at observed peak included all participants who received at least one dose of ZPIV or placebo and had any adverse events or immunogenicity data after dosing. The week 28 immunogenicity analysis population consisted of all participants who received ZPIV or placebo and had immunogenicity data available at week 28. This trial is registered with ClinicalTrials.gov, NCT02937233.

Walter Reed Army Institute of Research (WRAIR): Fifty Years of Achievements That Impact Science and Society

“…The overall statistical “probability of success” for regulatory approval of candidate vaccines to infectious diseases overall is estimated to be only 33.4%. 75 Therefore, with reluctance, I have excluded many first-in-human phase 1 trials of interesting and exciting candidate vaccines, including those to chikungunya virus, 76 Ebola and Marburg viruses, 77 Middle East respiratory syndrome virus, 78 , 79 and Zika virus, 80 because they have not yet been proved successful in a phase 3 trial and have not been licensed for human use by a national regulatory agency.…”

Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract.

“…Despite these results, recent studies with the same DNA vaccine found that it did not completely prevent adverse fetal outcomes in pregnant monkeys under prolonged ZIKV exposure (25). Another candidate vaccine-the Zika puri ed inactivated virus (ZPIV) vaccine failed to induce durable immune responses beyond eight weeks of vaccination in phase 1 clinical trials (36). This data suggests that further development in ZIKV vaccine strategies is paramount for the protection of susceptible pregnant women and their unborn fetuses.…”

Development of a gene-deleted live attenuated candidate vaccine against fish virus (ISKNV) with low pathogenicity and high protection

“…The diluted serums were mixed with ISKNV suspension of 100 TCID 50 in 96-well plates at a ratio of 1:1, followed by overnight incubation at 4 C. Then, 2 3 10 4 MFF-1 cells were added to the serum-virus mixture, and the plates were incubated for 5 days at 27 C in a 5% CO 2 incubator. The wells with enlarged cells were recorded under the microscopes, and the neutralization titers were expressed as MN 50 , which is the reciprocal of the serum dilution capable of neutralizing 50% of the test virus dose (Stephenson et al, 2020). Statistical analysis was performed using SPSS version 10.0.…”