China
Africa
Explore chapters and articles related to this topic
Out of Nowhere
Published in Rae-Ellen W. Kavey, Allison B. Kavey, Viral Pandemics, 2020
Rae-Ellen W. Kavey, Allison B. Kavey
This devastating Ebola pandemic led to immediate efforts to develop a vaccine to prevent and/or limit future outbreaks. A collaborative global effort coordinated by the WHO resulted in accelerated development of candidate vaccines funded by the US National Institutes of Health, the Wellcome Trust, the European Commission, the UK Medical Research Council and the Bill & Melinda Gates Foundation. After the attacks on the USA on September 11, 2001, several governments had invested in Ebola virus vaccine research because of concerns it could be used as a biological weapon.148 Based on results from these studies, candidate vaccines were rapidly designed, developed and manufactured in the US, Canada, Europe, and Asia with trials initiated in these countries plus Africa and Australia. A total of 10 clinical studies were conducted in support of potential eventual registration of an Ebola vaccine. With a lethal pathogen like Ebola, licensure is approved on the basis of animal studies plus evidence of safety and a proven immune response.149 Clinical trials used administration of the vaccine to healthy human subjects to evaluate the immune response and identify side effects in accelerated protocols. Viral-vectored vaccine candidates entered Phase I clinical trials including a recombinant replication-competent vesicular stomatitis virus (rVSV) model and a recombinant chimpanzee adenovirus serotype 3 (ChAd3), both encoding the EBOV glycoprotein. Both vectors were previously shown to be safe in human studies for other candidate vaccines. The rVSV-ZEBOV vaccine was studied in a trial involving 11,841 people in Guinea at the end of the epidemic in 2015. Among the 5837 people who received the vaccine, no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases of EVD occurring 10 days or more after vaccination among those who did not receive the vaccine. The rVSV vaccine had no severe safety concerns and was shown to be 100% efficacious and 75% effective at the cluster level, including herd immunity in unvaccinated cluster subjects.150,151
Review of Ebola virus disease in children – how far have we come?
Published in Paediatrics and International Child Health, 2021
Devika Dixit, Kasereka Masumbuko Claude, Lindsey Kjaldgaard, Michael T. Hawkes
rVSV-ZEBOV is a live viral vaccine with a porcine rhabdovirus engineered to express the ZEBOV surface glycoprotein. Two studies, the PREVAIL I study and the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) both conducted in 2015–2016 demonstrated the immunogenicity and safety of the rVSV-ZEBOV vaccine [126,127]. The Ébola Ça Suffit trial, an open-label cluster randomised ring vaccination trial in Guinea and Sierra Leone, demonstrated strong protective efficacy of rVSV-ZEBOV used in a ring-vaccination protocol [128]. The trial initially systematically excluded participants under 18 years of age; however, based on emerging evidence of efficacy, the protocol was later amended to include children >6 years of age, although this latter group was not randomised [128]. Overall, 194 children received rVSV-ZEBOV in this study with a good safety profile. Side-effects included headache (53%), fatigue (11%) and pain at the injection site (9%). Arthralgia occurred in 2% and lasted a mean 4.5 days [128]. In addition to its protective efficacy against EVD, in a recent study, vaccination with rVSV-ZEBOV was found to modulate disease severity [129]. In this study, only one of the 44 patients who had received the rVSV-ZEBOV vaccine was <18 years of age, reflecting persistent systematic exclusion of children from EVD vaccination programmes despite policy changes [129].
A tool with many applications: vesicular stomatitis virus in research and medicine
Published in Expert Opinion on Biological Therapy, 2020
Altar M. Munis, Emma M. Bentley, Yasuhiro Takeuchi
VSV aligns with the qualities of a good recombinant vaccine vector: capacity and genetic stability for insertion of transgenes, non-integrating viral life cycle with low toxicity, and ability to be produced in high-titers. In addition to the general lack of preexisting VSV immunity, the virus is relatively safe as it replicates in the host cell cytosol and does not integrate into the genome. Lastly, in preclinical studies, it has been demonstrated that VSV-based vaccines can induce strong humoral and cellular immune responses following administration [162,163]. For example, a single dose of recombinant VSV encoding hemagglutinin of influenza A and measles viruses can protect rodents against lethal challenges [164,165]. In addition to its use in tackling other infectious diseases such as hepatitis C [166], the most recent VSV success was the recombinant replication-competent VSV-based vaccine vector pseudotyped with the glycoprotein of Ebola virus (reviewed in [167]). After demonstrating full protection in preclinical non-human primate studies [168], the vector (rVSV-ZEBOV) was used during the outbreak in West Africa in 2013–2016 [169]. In this phase III trial, it was demonstrated that the vaccine was safe for use in human [170] and early data on its protective efficacy are very encouraging [171,172]. There is thus potential, with studies ongoing, to apply this recombinant VSV vaccine platform to other emerging viruses [173]. rVSV-ZEBOV vaccine, sold under brand name Erbevo, was approved for use in the US and EU in 2019 [174,175].
Durability of single-dose rVSV-ZEBOV vaccine responses: what do we know?
Published in Expert Review of Vaccines, 2018
Angela Huttner, Claire-Anne Siegrist
In the meantime, a previously planned, randomized phase 1 trial at the Walter Reed Army Institute of Research (WRAIR) was fast-tracked, such that this stateside study was launched nearly simultaneously with the VEBCON trials in Europe and Africa in the fall of 2014 [13]; a small phase I trial conducted in Canada launched soon thereafter [14]. These were thus the first studies to evaluate the vaccine’s immunogenicity in humans. Among their volunteers, only those in Kilifi, Kenya, Geneva, Switzerland, and Lambaréné, Gabon, were followed for at least 1 year, and only those in Switzerland and Gabon continue to be followed at present for the durability of their immune response. At the time of writing, over 10,000 people have since received the rVSV-ZEBOV vaccine, most in African field trials, both controlled and carried out at the end of the 2014–5 epidemic [15–17] or uncontrolled and conducted in later, smaller epidemics (e.g.NCT03161366). Yet no field trial to date has been able to investigate immunogenicity in parallel with clinical efficacy; because of logistic challenges, immunogenicity outcomes have not been investigated at all in most participants.