(Accessed 7 October 2017)
Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial
Selidji T. Agnandji, José F. Fernandes, Emmanuel B. Bache, Régis M. Obiang Mba, Jessica S. Brosnahan, Lumeka Kabwende, Paul Pitzinger, Pieter Staarink, Marguerite Massinga-Loembe, Verena Krähling, Nadine Biedenkopf, Sarah Katharina Fehling, Thomas Strecker, David J. Clark, Henry M. Staines, Jay W. Hooper, Peter Silvera, Vasee Moorthy, Marie-Paule Kieny, Akim A. Adegnika, Martin P. Grobusch, Stephan Becker, Michael Ramharter, Benjamin Mordmüller, Bertrand Lell, VEBCON Consortium , Sanjeev Krishna, Peter G. Kremsner
Research Article | published 06 Oct 2017 PLOS Medicine
Why was this study done?
:: The worst Ebola outbreak in history ended in 2016 after killing about 11,323 individuals and infecting 28,650 individuals worldwide.
:: This public health emergency accelerated efforts to develop a vaccine as part of the strategy to contain the outbreak.
:: Two vaccine candidates with preclinical safety and efficacy data obtained from non-human primates entered human trials.
:: The one used in our study is the rVSVΔG-ZEBOV-GP vaccine, containing a non-infectious portion of a gene from the Zaire Ebola virus introduced into a recombinant vesicular stomatitis virus (rVSV), which itself is unlikely to cause disease in humans.
:: To generate data for deployment of the vaccine, several dose-ranging phase I trials were initiated across centres in the United States, Europe, and Africa.
What did the researchers do and find?
:: We allocated 115 adults aged 18–50 years to receive 1 of the 5 doses used in the trial. A single intramuscular dose ranging from 3 × 103 to 2 × 107 plaque-forming units (PFU) was given, and participants were followed up until 6 months post-injection for safety and immunogenicity.
: Preliminary results led to the selection of the 2 × 107 PFU dose for further development.
We also included 20 adolescents (13–17 years) and 20 children (6–12 years), who received the 2 × 107 PFU dose and were followed-up in a similar way as the adults.
:: No vaccine-related serious or severe adverse event was reported by any participant.
:: A high proportion of our population—even though residing in an area with no history of Ebola outbreak—had pre-vaccination antibodies specific to the Zaire Ebola virus.
:: In adults, antibodies persisted up to 6 months post-injection at doses of 3 × 105 to 2 × 107 PFU.
:: In participants with baseline antibodies, a dose as low as 3 × 104 PFU could induce high antibody titres up to day 56 post-injection.
: Higher vaccine replication, leading to shedding of the vaccine in saliva and urine, occurred in children and adolescents.
What do these findings mean?
:: Our results and other findings show that this vaccine is safe and immunogenic.
:: Lower vaccine doses may be needed in paediatric populations as well as for boosting after primary vaccination or naturally acquired immunity.
When cost-effective interventions are unaffordable: Integrating cost-effectiveness and budget impact in priority setting for global health programs
Alyssa Bilinski, Peter Neumann, Joshua Cohen, Teja Thorat, Katherine McDaniel, Joshua A. Salomon
Essay | published 02 Oct 2017 PLOS Medicine
:: Many health interventions deemed cost-effective are not affordable. Despite the importance of affordability to policymakers, little of the cost-effectiveness literature in global health addresses this issue.
:: Budget impact analysis (BIA) describes an intervention’s short-term costs and savings from the payer’s perspective.
:: Researchers should report BIA alongside cost-effectiveness analysis (CEA). When CEA and BIA lead to different conclusions, researchers should explain why.
:: Policymakers should recognize that not all cost-effective interventions are affordable and interpret information about cost-effectiveness in the context of their budget and other available funding sources.
:: Both cost-effectiveness and affordability should be reflected in the design of essential health service packages.