Immunogenicity and Vaccine Shedding After 1 or 2 Doses of rVSVΔG-ZEBOV-GP Ebola Vaccine (ERVEBO®): Results From a Phase 2, Randomized, Placebo-controlled Trial in Children and Adults.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older. METHODS: The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1-17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSVΔG-ZEBOV-GP, 2-dose rVSVΔG-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Furthermore, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR. RESULTS: In total, 819 children and 783 adults were randomized to receive rVSVΔG-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSVΔG-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSVΔG-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2. CONCLUSIONS: A single dose of rVSVΔG-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSVΔG-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18).

Evaluation of Pre-Hematopoietic Cell Transplantation (HCT) Brain MRI and Neurologic Complications of Pediatric Patients Undergoing HCT for Hematologic Malignancies.

Adverse neurologic complications (NC) occur commonly in pediatric patients with hematologic malignancies both pre- and post-allogeneic hematopoietic cell transplant (HCT). Given this known risk, we previously obtained pre-HCT brain magnetic resonance imaging (MRI) to document baseline abnormalities but utility of this and findings are not well described. This study aimed to ( a) determine the prevalence and risk factors for abnormal brain MRI and ( b) determine prevalence and risk factors for development of new NC during and 2 years post-HCT. Retrospective chart review included 102 patients with hematologic malignancies who underwent allogeneic HCT between 2000 and 2009 at University of California San Francisco (UCSF) Children's Hospital and included standard HCT data, brain MRI reports, and NC and symptoms pre- and post-HCT. Forty-three percent of patients had abnormal findings on pre-MRI, most commonly nonspecific white matter changes. Neurologic symptoms pre-HCT was the only significant risk factor for abnormal MRI. Eleven patients (11%) developed post-HCT NC. Non-Caucasian race was the only significant risk factor for new NC. Although abnormal pre-HCT brain MRI is common, these findings are not predictive of subsequent NC post-HCT. Therefore routine surveillance may not be informative for that purpose, particularly when general anesthesia is required, which can have detrimental neurocognitive effects. Etiology of NC in pediatric HCT is likely multifactorial and may include genetic and ethnic predispositions.