Ebola vaccines - Where are we?
Ontology highlight
ABSTRACT:
SUBMITTER: Watle SV
PROVIDER: S-EPMC5084983 | biostudies-other | 2016 Oct
REPOSITORIES: biostudies-other
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Project description:After killing more than 11,000 people in West Africa, the largest known outbreak of the deadly Ebola virus has largely subsided-but development of effective antiviral countermeasures remains a concern. Several experimental products show promise.
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Project description: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 virus-based 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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Project description:The 2013 Ebola virus outbreak in West Africa, as of writing, is declining in reported human cases and mortalities. The resulting devastation caused highlights how health systems, in particular in West Africa, and in terms of global pandemic planning, are ill prepared to react to zoonotic pathogens. In this paper we propose One Health as a strategy to prevent zoonotic outbreaks as a shared goal: that human and Great Ape vaccine trials could benefit both species. Only recently have two phase 2/3 Ebola human vaccine trials been started in West Africa. This paper argues for a conceptual change in pandemic preparedness. We first discuss the ethics of One Health. Next, we focus on the current Ebola outbreak and defines its victims. Third, we present the notion of a 'shared benefit' approach, grounded in One Health, and argue for the vaccination of wild apes in order to protect both apes and humans. We believe that a creation of such inter-species immunity is an exemplar of One Health, and that it is worth pursuing as a coextensive public health approach.
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Project description:Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials.
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Project description:Ebola virus (EBOV) is among the deadliest pathogens known to man causing infrequent outbreaks of hemorrhagic disease. In humans, the case fatality rates in the outbreaks can reach 90%. During the West African epidemic almost 30,000 people were infected and of these over 11,000 fatalities were reported. Currently, we are facing an uncontained larger outbreak in the Democratic Republic of the Congo. Even though EBOV was discovered in 1976, extensive efforts to develop countermeasures, particularly therapeutics and vaccines, started late and there is still no FDA-approved product available. Nevertheless, one candidate vaccine, the rVSV-ZEBOV, is being used in clinical trials during the current outbreak with the hope of ending the human transmission chains. However, adverse reactions to administration of some EBOV vaccines have been reported; therefore, we have developed a safe and efficacious formulation of insect-cell derived adjuvanted protein vaccines. Vaccine candidates containing the EBOV glycoprotein with or without matrix proteins VP24 and VP40 formulated with one of three different adjuvants were tested in guinea pigs for immunogenicity and efficacy against lethal EBOV challenge. The results demonstrated that these vaccine candidates engendered high titers of antigen-specific antibodies in immunized animals and two of these vaccine candidates afforded complete or nearly complete protection against lethal challenge. Interestingly, we found a sex bias in partially protected immunized groups with male guinea pigs succumbing to disease and females surviving. In summary, we developed a safe and immunogenic adjuvanted subunit vaccine uniformly protective against EBOV disease in guinea pigs.
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Project description:For Ebola virus (EBOV), 4 different species are known: Zaire, Sudan, Côte d'Ivoire, and Reston ebolavirus. The newly discovered Bundibugyo ebolavirus has been proposed as a 5th species. So far, no cross-neutralization among EBOV species has been described, aggravating progress toward cross-species protective vaccines. With the use of recombinant vesicular stomatitis virus (rVSV)-based vaccines, guinea pigs could be protected against Zaire ebolavirus (ZEBOV) infection only when immunized with a vector expressing the homologous, but not a heterologous, EBOV glycoprotein (GP). However, infection of guinea pigs with nonadapted wild-type strains of the different species resulted in full protection of all animals against subsequent challenge with guinea pig-adapted ZEBOV, showing that cross-species protection is possible. New vectors were generated that contain EBOV viral protein 40 (VP40) or EBOV nucleoprotein (NP) as a second antigen expressed by the same rVSV vector that encodes the heterologous GP. After applying a 2-dose immunization approach, we observed an improved cross-protection rate, with 5 of 6 guinea pigs surviving the lethal ZEBOV challenge if vaccinated with rVSV-expressing SEBOV-GP and -VP40. Our data demonstrate that cross-protection between the EBOV species can be achieved, although EBOV-GP alone cannot induce the required immune response.
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Project description:The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primates against ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first-generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately tenfold lower vaccine-associated viraemia compared to the first-generation vaccine and both provided complete, single-dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV.
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Project description:Zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in West Africa. Previously, we showed that a whole Ebola virus (EBOV) vaccine based on a replication-defective EBOV (EBOVΔVP30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted EBOV. Here, we demonstrate that EBOVΔVP30 protects nonhuman primates against lethal infection with EBOV. Although EBOVΔVP30 is replication-incompetent, we additionally inactivated the vaccine with hydrogen peroxide; the chemically inactivated vaccine remained antigenic and protective in nonhuman primates. EBOVΔVP30 thus represents a safe, efficacious, whole-EBOV vaccine candidate that differs from other EBOV vaccine platforms in that it presents all viral proteins and the viral RNA to the host immune system, which might contribute to protective immune responses.
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Project description:The filoviruses Ebola virus and Marburg virus are among the most dangerous pathogens in the world. Both viruses cause viral hemorrhagic fever, with case fatality rates of up to 90%. Historically, filovirus outbreaks had been relatively small, with only a few hundred cases reported. However, the recent West African Ebola virus outbreak underscored the threat that filoviruses pose. The three year-long outbreak resulted in 28,646 Ebola virus infections and 11,323 deaths. The lack of Food and Drug Administration (FDA) licensed vaccines and antiviral drugs hindered early efforts to contain the outbreak. In response, the global scientific community has spurred the advanced development of many filovirus vaccine candidates. Novel vaccine platforms, such as viral vectors and DNA vaccines, have emerged, leading to the investigation of candidate vaccines that have demonstrated protective efficacy in small animal and nonhuman primate studies. Here, we will discuss several of these vaccine platforms with a particular focus on approaches that have advanced into clinical development.
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Project description:During the 2014-2016 Ebola epidemic, Médecins Sans Frontières (MSF) treated Ebola-positive pregnant women in its Ebola Treatment Centers (ETCs). For pregnant women with confirmed Ebola virus disease, inclusion in clinical vaccine/drug/therapeutic trials was complicated. Despite their extremely high Ebola-related mortality in previous epidemics (89-93%) and a neonatal mortality of 100%, theoretical concerns about safety of vaccines and therapeutics in pregnancy were invoked, limiting pregnant women's access to an experimental live attenuated vaccine and brincidofovir, an experimental antiviral. Favipiravir, another experimental antiviral, was made available to pregnant women only after extensive negotiations and under a 'Monitored Emergency Use of Unregistered and Experimental Interventions' (MEURI) protocol. This paper describes the case of a pregnant woman who presented to the ETCs near the end of the Ebola epidemic in Guinea. The pregnant patient was admitted with confirmed Ebola disease. She was previously denied access to potentially protective vaccination due to pregnancy, and access to experimental ZMapp was only possible through a randomized clinical trial (presenting a 50% chance of not receiving ZMapp). She received favipiravir, but died of Ebola-related complications. The infant, born in the ETC, tested positive for Ebola at birth. The infant received ZMapp (under MEURI access outside of the clinical trial), an experimental drug GS5734, and a buffy coat of an Ebola survivor, and survived. Though the infant did have access to experimental therapeutics within 24 h of birth, access to other experimental compounds for her mother was denied, raising serious ethical concerns.
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