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  • Where does this leave the other potential

    2019-04-15

    Where does this leave the other potential vaccines, and what additional information is required to inform their use? Many of these vaccines are based on a non-replicating adenoviral vector modified to express the Ebola glycoprotein (eg, adenovirus 5 (Ad5-ZEBOV), chimpanzee adenovirus 3 (Chad3), or adenovirus 26 (AD26-ZEBOV), which could potentially be used in heterologous prime/boost schedules together with a vaccine that uses an alternative viral vector bearing the same or similar Ebola tyrosine kinase inhibitors (eg, MVA-BN-Filo). Although most published clinical data on these vaccines are from phase 1 studies conducted in Europe, North America, and China, numerous studies are ongoing or recently completed in sub-Saharan Africa, including a phase 2 Ad5-ZEBOV study conducted in Sierra Leone, recently published in the . For all the candidate Ebola vaccines, a crucial, and as yet unknown, characteristic is the long-term persistence of the vaccine-induced response. Ebola virus has been detected in the seminal fluid of survivors of Ebola virus disease 401 days after infection, and sexual transmission has been documented. A review by the Wellcome Trust-CIDRAP Ebola Vaccine Team B initiative suggested that any vaccine used for responsive immunisation of disease contacts should optimally induce protection that lasts 2 years. The same review suggested that any immunisation schedule employed in a pre-emptive campaign in at-risk populations such as health-care workers (an intervention that might curtail Ebola virus disease outbreaks more efficiently than responsive campaigns) would ideally provide 10 years\' protection. No data are currently available on the duration of humoral immunity induced by immunisation with VSV-EBOV, although follow-on studies are underway. Data on the persistence of immune responses induced by other vaccine candidates are emerging, and in this issue of Jing-Xin Li and colleagues describe the persistence of humoral and cellular immunity for approximately 6 months following a single dose of Ad5-ZEBOV, and 1 year following a booster dose with the same vaccine (homologous prime/boost). Interpretation of these data is complicated by interlaboratory variability in the assays used in different clinical trials, the lack of a known immunological correlate of protection, and whether a correlate identified for the one vaccine with evidence of effectiveness (VSV-EBOV, using a replicating viral vector) would apply equally to immunity induced by a vaccine such as Ad5-ZEBOV that uses a non-replicating viral vector. Nevertheless, Li and colleagues\' study suggests that 6 months after a dose of Ad5-ZEBOV administered to healthy adults in China, Ebola-glycoprotein-specific IgG concentrations were less than half that of their post-immunisation peak. These data are concerning, but more concerning still is the eight-fold fall in specific IgG observed at the same dose in the Sierra Leonean study. Specific IgG concentrations were increased by a booster dose of Ad5-ZEBOV in the Chinese study; however, the specific T-cell response (measured by interferon gamma ELISPOT) following the Ad5-ZEBOV boosting appeared to be lower post-boost than post-prime. By 1-year post booster, specific IgG concentrations had fallen 14-fold from the post-boost peak, and were no higher than those at 28 days post priming. No data on a booster-dose response in the Sierra Leonean study are available. The rapid waning of immunity post-priming and post-booster might be related to high background immunity to the Ad5 viral vector in both the Chinese and Sierra Leonean population, and the rapid post-boost decline could have been exacerbated by using AD5-ZEBOV for both priming and boosting. This post-booster response appears to be more persistent for schedules using the heterologous prime-boost schedules such as Ad26-ZEBOV/MVA-BN-Filo; when these vaccines were given 56 days apart, IgG concentrations at 180 days post boost had fallen three-fold from the post-boost peak but remained three to four times higher than at day 28 post-prime.