The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial

Huttner, Angela; Dayer, Julie-Anne; Yerly, Sabine; Combescure, Christophe; Auderset, Floriane; Desmeules, Jules Alexandre; Eickmann, Markus; Finckh, Axel; Gonçalves, Ana Rita; Hooper, Jay W.; Kaya, Gürkan; Krähling, Verena; Kwilas, Steve; Lemaître, Barbara; Matthey, Alain; Silvera, Peter; Becker, Stephan; Fast, Patricia E.; Moorthy, Vasee; Kiény, Marie Paule; Kaiser, Laurent; Siegrist, Claire‐Anne

doi:10.1016/s1473-3099(15)00154-1

Cited by 264 publications

(317 citation statements)

References 31 publications

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“…After preliminary data indicated tolerability and immunogenicity of low vaccine doses in other studies, the study was resumed in Geneva, but at a lower dose of 3 × 10 5 pfu, comparing outcomes to those of vaccinees who had received the higher doses before the study was put on hold. 26 Patterns of detectable viremia were comparable with other studies that investigated the rVSVΔG-ZEBOV-GP vaccine; viremia was transient, peaking by day 3 and no longer evident on day 7. 16,24,26 Glycoprotein-binding serum antibodies were detectable in all vaccinated individuals, irrespective of vaccine dose.…”

Section: Discussionsupporting

confidence: 81%

Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial

ElSherif

Brown

MacKinnon‐Cameron

et al. 2017

CMAJ

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Section: Discussionsupporting

confidence: 81%

Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial

ElSherif

Brown

MacKinnon‐Cameron

et al. 2017

CMAJ

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“…Vaccines that were assessed in phase I and/or II studies during the 2013-2016 EBOV epidemic include rVSV-EBOV [268][269][270][271][272] , Ad5-EBOV [273][274][275] , rVSV-EBOV combined with rAd5-EBOV 276 , ChAd3-EBOV with or without MVA-EBOV [277][278][279][280] , Ad26-EBOV combined with MVA-EBOV 281 , and DNA encoding multiple filovirus GPs 282,283 . These EBOV vaccines generally elicited good immunogenicity against EBOV GP, and no serious adverse events were described.…”

Section: Vaccination Of Humansmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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“…Therefore, another 56 participants were recruited to continue this trial, with 43 of them were randomly assigned to receive lower dose rVSV-EBOV of 3 £ 10 5 vp or placebo and 13 only received open-label rVSV-EBOV at 3 £ 10 5 vp (NCT02287480). 54 The results showed that the dose reduction to 3 £ 10 5 vp could decreased the occurrence of viremia, but 13 low-dose vaccinees (25%) still occurred arthralgia after immunization. Additionally, another 2 participants reported purpura on the lower legs and the counts of lymphocyte, neutrophil, and platelet decreased significantly at day 1-3 post-vaccination.…”

Section: Rvsv-ebovmentioning

confidence: 93%

Ebola vaccines in clinical trial: The promising candidates

Wang

et al. 2016

Human Vaccines & Immunotherapeutics

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Ebola virus disease (EVD) has become a great threat to humans across the world in recent years. The 2014 Ebola epidemic in West Africa caused numerous deaths and attracted worldwide attentions. Since no specific drugs and treatments against EVD was available, vaccination was considered as the most promising and effective method of controlling this epidemic. So far, 7 vaccine candidates had been developed and evaluated through clinical trials. Among them, the recombinant vesicular stomatitis virusbased vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial. However, several concerns were still associated with the Ebola vaccine candidates, including the safety profile in some particular populations, the immunization schedule for emergency vaccination, and the persistence of the protection. We retrospectively reviewed the current development of Ebola vaccines and discussed issues and challenges remaining to be investigated in the future.

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The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial

Abstract: Wellcome Trust through WHO.

Cited by 264 publications

References 31 publications

Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial

Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial

Post-exposure treatments for Ebola and Marburg virus infections

Ebola vaccines in clinical trial: The promising candidates

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