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Persistence of antibodies produced in response to recombinant vesicular stomatitis virus-Ebolavirus vaccines

September 13, 2018

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Previous studies have found that the recombinant vesicular stomatitis virus (rVSV) vaccine that expresses Zaire Ebolavirus (ZEBOV) glycoproteins is efficacious in the weeks following single-dose injection. However, the duration of this immunity is unknown. The authors examined the persistence of antibodies at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV during three previous trials. They conducted an observational cohort study in which 217 vaccine recipients were prospectively followed up from the African and European phase 1 rVSV-ZEBOV trials. Each were vaccinated once in 2014-15 with 300,000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence. Of the 217 recipients (102 from the Geneva study, 75 from the Lambaréné study and 40 from the Kilifi study), 197 returned and provided samples at 1 year (95 from the Geneva study, 63 from the Lambaréné and 39 from the Kilifi study) and 90 at 2 years (all from the Geneva study). In the Geneva group, 100% of 44 high-dose recipients that were seropositive at day 28 remained seropositive at 2 years, while 89% of 37 low-dose recipients were seropositive for 2 years. In the high-dose recipients, ZEBOV glycoprotein IgG geometric mean concentrations (GMCs) decreased significantly between their peak at 1-3 months and month 6 following vaccination in Geneva and Lambaréné, but not in Kilifi, and then remained stable at all sites apart from Geneva, where GMC high-dose recipients increased significantly between 6 months and 1 year. Antibody persistence was found to be similar between 6 months and 1 year in those who had received low-dose vaccine, but with lower titres seen among Geneva recipients at 2 years than at 1 year after vaccination (GMC ratio 0·61, 95%CI 0·49-0·77). In multivariate analyses, the predictors of increased IgG GMCs beyond 6 months included high-dose vs. low-dose vaccination and vaccine-related arthritis; but not sex, age or baseline seropositivity. Neutralising antibodies were found to be less durable, with seropositivity dropping from 64-71% at 28 days to 27-31% at 6 months in Geneva recipients. Therefore antibody responses to single-dose rVSV-ZEBOV vaccination are sustained across dose ranges and settings.

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Huttner A, Agnandji ST, Combescure C, Fernandes JF, Bache EB, et al. ISSN: Lancet Infect Dis; 18(7): 738-748

2018

Added: September 13, 2018