The humoral antibody response of a single injection of the rVSV-ZEBOV (recombinant vesicular stomatitis virus vaccine expressing the Zaire Ebola virus glycoprotein) was sustained for 1 to 2 years across dose ranges in both European and African populations, according to a study recently published in the Lancet Infectious Diseases.
The rVSV-ZEBOV vaccine was found to be efficacious up to 12 weeks after single-dose injection. It is recommended that any vaccine for the immunization of disease contacts should induce protection that lasts at least 2 years. This goal has not yet been reported for rVSV-ZEBOV. In human beings, rVSV-ZEBOV-induced antibodies that provide protection include neutralizing and nonneutralizing antibodies to the ZEBOV glycoprotein. Thus, this antibody persistence in vaccinated people may best estimate the durability and protection of the rVSV-ZEBOV vaccination.
This study assessed antibody persistence at 1 and 2 years in African and European volunteers who received a single dose of rVSV-ZEBOV in phase 1 trials (ClinicalTrials.gov identifiers: Geneva, NCT02287480 and NCT02933931; Kilifi, NCT02296983; Pan-African Clinical Trials Registry: Lambaréné, PACTR201311000919191). Participants were vaccinated with either a low dose (300,000 plaque-forming units) or high dose (10-15 million plaque-forming units) in 2014 to 2015 and were assessed for ZEBOV glycoprotein (IgG) antibody persistence and ZEBOV glycoprotein-specific IgG geometric mean concentrations (GMCs). Current GMCs were measured yearly by ELISA and compared with GMCs 28 days after immunization.
Of the 217 vaccines from the original studies, 197 provided samples at 1 year (Geneva, n=95; Lambaréné, n=63; Kilifi, n=39) and 90 at 2 years (all from the Geneva study).
rVSV-ZEBOV-induced response shows durability 1 to 2 years after a single injection. All participants in all groups who received a high-dose vaccine remained seropositive after 1 year. Furthermore, all Geneva group participants who received a high-dose vaccine remained seropositive after 2 years, whereas 89% of low-dose vaccinees remained seropositive for 2 years (P =.042). Delayed seropositivity responses were seen in participants given the low-dose (Geneva, 80% at 1 year, 91% at 2 years; Lambaréné, 85% at 28 days, 100% at 1 year; P =.244).
Participants who received a high dose showed a significant decrease in GMCs between their peak (1-3 months) and month 6 after vaccination in Geneva (P <.0001) and Lambaréné (P =.0298), but not in Kilifi (P =.5833). Among all doses, GMCs plateaued between 6 and 12 months across all sites, and up to 2 years in participants given a high-dose vaccine in the Geneva study. These GMCs remained stable except for in the Geneva group, in which GMCs increased significantly between 6 to 12 months (P =.0264). GMCs of low-dose participants resembled those of high-dose participants by 1 year postvaccination, and by 2 years, GMCs in these participants were 1 to 6 times higher than on day 28.
In multivariable analyses, predictors of increased IgG GMCs beyond 6 months included high-dose vs low-dose vaccination (Geneva, P =.0133; Lambaréné, P =.008) and vaccine-related arthritis (P =.0176), but not sex, age, or baseline seropositivity (all P >.05).
On the basis of the results, study authors concluded that “given the logistical challenges inherent in vaccine campaigns in Ebola-endemic regions, the importance of single-injection vaccination goes beyond mere convenience.”
Huttner A, Agnandji ST, Combescure C, et al; VEBCON; VSV-EBOVAC; VSV-EBOPLUS Consortia. Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study [published online April 4, 2018]. Lancet Infect Dis. doi: 10.1016/S1473-3099(18)30165-8