Ebola Vaccination: If Not Now, When?
Authors: Alison P. Galvani, Martial L. Ndeffo-Mbah, Natasha Wenzel, James E. Childs
Journal: Annals of Internal Medicine (2014)

Ideas and Opinions18 November 2014Ebola Vaccination: If Not Now, When?FREEAlison P. Galvani, PhD, Martial L. Ndeffo-Mbah, PhD, Natasha Wenzel, MPH, and James E. Childs, PhDAlison P. Galvani, PhDFrom Yale School of Public Health and Yale University, New Haven, Connecticut., Martial L. Ndeffo-Mbah, PhDFrom Yale School of Public Health and Yale University, New Haven, Connecticut., Natasha Wenzel, MPHFrom Yale School of Public Health and Yale University, New Haven, Connecticut., and James E. Childs, PhDFrom Yale School of Public Health and Yale University, New Haven, Connecticut.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-1904 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Ebola virus disease causes severe hemorrhagic fever, with a case-fatality rate of 50% to 90% (1). The ongoing epidemic in West Africa is the largest Ebola outbreak ever recorded and is rapidly crossing borders. The relentless epidemiologic trajectory and geographic dissemination represent a public health crisis that shows no signs of diminishing under current efforts. We believe that the time to deploy Ebola vaccines is now, as advocated in recent statements by the World Health Organization. Ebola arises sporadically via zoonosis from fruit bats (the natural reservoir) to humans, often through great apes. Human-to-human transmission occurs primarily through contact with infected body fluids. This transmission route puts health care workers, family members, and persons preparing bodies for traditional funerals at high risk for the disease (1). Although no Ebola vaccines are currently licensed, many candidates have been developed in the past decade. A DNA vaccine has been shown to be safe and immunogenic in a phase 1 clinical trial (2). In addition, a therapeutic vaccine based on recombinant vesicular stomatitis viruses (rVSVs) expressing Ebola virus surface glycoprotein was found to confer prophylactic and postexposure protection in nonhuman primates (3). Despite the promise of these and other Ebola vaccine candidates, none have advanced to late-stage human trials and licensure. The challenge in this process has been the inability to evaluate vaccine efficacy in human populations given the sporadic nature of Ebola outbreaks.For unique circumstances, such as those where conventional efficacy trials are not feasible, the U.S. Food and Drug Administration has created the "animal rule," which states that licensure can be approved on the basis of animal model studies that replicate human disease combined with safety and immunologic data from humans (4). Nonhuman primates serve as the gold standard for animal models of Ebola infection and have been used to test Ebola vaccine candidates, with promising results (Table). Alternate vaccine candidates have specific properties that must be taken into consideration for selection of the ideal vaccine under given circumstances. For example, one that requires several weeks to develop immunogenicity, such as the recombinant adenovirus–based DNA vaccine, could be appropriate in high-risk settings not currently affected by an Ebola outbreak (2). Similarly, a vaccine that remains viable at ambient temperatures, such as the Ebola subunit vaccine (5), could be stockpiled as part of a preparedness strategy. In contrast, the species-specific properties of a recombinant cytomegalovirus vaccine make it a candidate for wildlife vaccination in Ebola-endemic areas (6). Although a wildlife vaccination strategy would not be the focus of a containment strategy to control an outbreak already in a human population, it may be a component of a longer-term strategy to reduce Ebola zoonosis. With regard to the current outbreak, given that the rVSV vaccine has shown efficacy in eliciting both prophylactic and postexposure protection (3), it is probably the vaccine of choice for persons in a high-risk setting who may have already been exposed. The rVSV vaccine has also been found to be effective in primates infected with simian immunodeficiency virus (7) and may therefore be particularly well-suited for use in populations with a high prevalence of HIV. We believe that the safety risks of vaccines, particularly those found to be safe in phase 1 clinical trials, are probably negligible compared with the risks faced by health care workers in communities where the highly virulent Ebola virus is currently circulating.Table. Viable Ebola Vaccine CandidatesPossible strategies could include the vaccination of health care workers in high-risk regions. Ideally, the vaccine would be administered as soon as possible and before exposure. Nevertheless, the postexposure efficacy of the rVSV vaccine is reassuring in the context of the current outbreak, where health care workers may already have been inadvertently exposed. Another strategy that would complement the vaccination of health care workers is postexposure "ring" vaccination and quarantine of those who have probably been exposed to the virus, including vaccinating close contacts of infected persons. The rVSV vaccine would be promising for both of these target groups given its prophylactic and postexposure efficacies compared with other vaccine candidates that are slower to elicit a protective immunologic response. Epidemiologic modeling can facilitate the optimization of such vaccination strategies when vaccine supply is limited and production has to be scaled up. Primarily, an Ebola vaccine could mitigate disease transmission and protect health care workers, thus enabling an effective medical and epidemiologic response in affected areas. Secondarily, the emergency deployment of an Ebola vaccine may also serve as a source of data that could be used to further demonstrate efficacy and waning properties that are fundamental to informing preparedness strategies to prevent future outbreaks.Vaccination alone is no panacea. Cultural and socioeconomic factors and suspicion of Western medical approaches complicate all medical interventions. Epidemiologic practices, such as trace-back investigations to identify and quarantine persons exposed to Ebola, are pivotal to controlling spread. Such control methods require trained personnel on the ground in even the most remote locations. Given that nosocomial transmission has contributed substantially to past Ebola outbreaks (1), it is also imperative to integrate vaccination with nosocomial contact precautions and quarantining.Although vaccine production, transport, and cost are undeniable logistical challenges to any vaccination strategy, the resources required to implement vaccination should be made available by the international community given the magnitude of the threat that the current Ebola outbreak poses to countries in which transmission is occurring and to which it may spread. Even from a pragmatic perspective, it is in the interest of the international community to assist West Africa in containing the Ebola outbreak. Curtailing an outbreak is always easier in its earliest stages than after it has disseminated geographically. That window of opportunity may be rapidly closing.References1. Khan AS, Tshioko FK, Heymann DL, LeGuenno B, Nabeth P, Kerstiëns B, et al. The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis. 1999;179 Suppl 1 S76-86. [PMID: 9988168] MedlineGoogle Scholar2. Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, et al. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol. 2006;13:1267-77. [PMID: 16988008] CrossrefMedlineGoogle Scholar3. Feldmann H, Jones SM, Daddario-DiCaprio KM, Geisbert JB, Ströher U, Grolla A, et al. Effective post-exposure treatment of Ebola infection. PLoS Pathog. 2007;3:e2. [PMID: 17238284] CrossrefMedlineGoogle Scholar4. Sullivan NJ, Martin JE, Graham BS, Nabel GJ. Correlates of protective immunity for Ebola vaccines: implications for regulatory approval by the animal rule. Nat Rev Microbiol. 2009;7:393-400. [PMID: 19369954] doi:10.1038/nrmicro2129 CrossrefMedlineGoogle Scholar5. Phoolcharoen W, Dye JM, Kilbourne J, Piensook K, Pratt WD, Arntzen CJ, et al. A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge. Proc Natl Acad Sci U S A. 2011;108:20695-700. [PMID: 22143779] doi:10.1073/pnas.1117715108 CrossrefMedlineGoogle Scholar6. Tsuda Y, Caposio P, Parkins CJ, Botto S, Messaoudi I, Cicin-Sain L, et al. A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus. PLoS Negl Trop Dis. 2011;5:e1275. [PMID: 21858240] doi:10.1371/journal.pntd.0001275 CrossrefMedlineGoogle Scholar7. Geisbert TW, Daddario-Dicaprio KM, Lewis MG, Geisbert JB, Grolla A, Leung A, et al. Vesicular stomatitis virus-based Ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. PLoS Pathog. 2008;4:e1000225. [PMID: 19043556] doi:10.1371/journal.ppat.1000225 CrossrefMedlineGoogle Scholar8. Blaney JE, Wirblich C, Papaneri AB, Johnson RF, Myers CJ, Juelich TL, et al. Inactivated or live-attenuated bivalent vaccines that confer protection against rabies and Ebola viruses. J Virol. 2011;85:10605-16. [PMID: 21849459] doi:10.1128/JVI.00558-11 CrossrefMedlineGoogle Scholar9. Warfield KL, Swenson DL, Olinger GG, Kalina WV, Aman MJ, Bavari S. Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge. J Infect Dis. 2007;196 Suppl 2 S430-7. [PMID: 17940980] CrossrefMedlineGoogle Scholar10. Bukreyev A, Yang L, Zaki SR, Shieh WJ, Rollin PE, Murphy BR, et al. A single intranasal inoculation with a paramyxovirus-vectored vaccine protects guinea pigs against a lethal-dose Ebola virus challenge. J Virol. 2006;80:2267-79. [PMID: 16474134] CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Yale School of Public Health and Yale University, New Haven, Connecticut.Grant Support: By the National Institutes of Health (NIH 2 U01 GM087719 and 5 U01 GM105627).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1904.Corresponding Author: Alison P. Galvani, PhD, Center for Infectious Disease Modeling, Yale School of Public Health, PO Box 208034, 60 College Street, New Haven, CT 06520-8034; e-mail, alison.[email protected]edu.Current Author Addresses:Drs. Galvani and Ndeffo-Mbah and Ms. Wenzel: Center for Infectious Disease Modeling, Yale School of Public Health, PO Box 208034, 60 College Street, New Haven, CT 06520-8034.Dr. Childs: Department of Epidemiology (Microbial Diseases), Yale School of Public Health, PO Box 208034, 60 College Street, New Haven, CT 06520-8034.Author Contributions:Conception and design: A.P. Galvani, J.E. Childs.Analysis and interpretation of the data: J.E. Childs.Drafting of the article: A.P. Galvani, M.L. Ndeffo-Mbah, N. Wenzel.Critical revision of the article for important intellectual content: A.P. Galvani, J.E. Childs.Final approval of the article: A.P. Galvani, M.L. Ndeffo-Mbah, N.Wenzel, J.E. Childs.Obtaining of funding: A.P. Galvani.Administrative, technical, or logistic support: N. Wenzel.Collection and assembly of data: N. Wenzel.This article was published online first at www.annals.org on 21 August 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEbola Fever: Reconciling Planning With Risk in U.S. Hospitals Michael Klompas , Daniel J. Diekema , Neil O. Fishman , and Deborah S. Yokoe Protecting Health Care Workers From Ebola: Personal Protective Equipment Is Critical but Is Not Enough William A. Fischer II , Noreen A. Hynes , and Trish M. Perl Serotherapy for Ebola: Back to the Future Scott H. Podolsky Ebola, Ethics, and Public Health: What Next? Nancy Kass Ebola Hemorrhagic Fever in 2014: The Tale of an Evolving Epidemic Carlos del Rio , Aneesh K. Mehta , G. Marshall Lyon III , and Jeannette Guarner Serotherapy for Ebola: Back to the Future Scott H. Podolsky Ebola Hemorrhagic Fever in 2014: The Tale of an Evolving Epidemic Carlos del Rio , Aneesh K. Mehta , G. Marshall Lyon III , and Jeannette Guarner Ebola, Ethics, and Public Health: What Next? Nancy Kass Protecting Health Care Workers From Ebola: Personal Protective Equipment Is Critical but Is Not Enough William A. Fischer II , Noreen A. Hynes , and Trish M. Perl Ebola Fever: Reconciling Planning With Risk in U.S. Hospitals Michael Klompas , Daniel J. Diekema , Neil O. Fishman , and Deborah S. Yokoe Metrics Cited ByExperimental analysis of T cell epitopes for designing liver cancer vaccine predicted by system-level immunoinformatics approachLessons learned from engaging communities for Ebola vaccine trials in Sierra Leone: reciprocity, relatability, relationships and respect (the four R's)Pharmacoinformatics-based identification of potential bioactive compounds against Ebola virus protein VP24Vertical dynamics of Ebola with media impactEbola vaccination in the Democratic Republic of the CongoA MATHEMATICAL MODEL FOR EBOLA EPIDEMIC WITH SELF-PROTECTION MEASURESControl fast or control smart: When should invading pathogens be controlled?Liver Disease Associated With Systemic Viral InfectionEbola virus: A gap in drug design and discovery - experimental and computational perspectiveLaboratory diagnosis of Ebola virus disease and corresponding biosafety considerations in the China Ebola Treatment CenterNext Steps for Ebola Vaccination: Deployment in Non-Epidemic, High-Risk SettingsEbola, gender and conspicuously invisible women in global health governanceRecent advances in the development of vaccines for Ebola virus diseaseModeling the effect of comprehensive interventions on Ebola virus transmissionEpitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics studyJournal Roundup: Ebola, antibiotic use and abuse, and the usual suspectsÉbola y virus emergentesEffect of Ebola Progression on Transmission and Control in LiberiaDan Yamin, PhD, Shai Gertler, Martial L. Ndeffo-Mbah, PhD, Laura A. Skrip, MPH, Mosoka Fallah, PhD, Tolbert G. Nyenswah, MPH, Frederick L. Altice, MD, MA, and Alison P. Galvani, PhDEbola virus (EBOV) infection: Therapeutic strategiesTactics and Strategies for Managing Ebola Outbreaks and the Salience of ImmunizationDynamics and control of Ebola virus transmission in Montserrado, Liberia: a mathematical modelling analysisEbola in West Africa: be aware and prepareEbola control: effect of asymptomatic infection and acquired immunity 18 November 2014Volume 161, Issue 10Page: 749-750KeywordsComputed axial tomographyEbola virusEpidemiologyHealth care providersInfectious diseasesPopulation statisticsPrevention, policy, and public healthQuarantinesSafetyVaccines ePublished: 18 November 2014 Issue Published: 18 November 2014 CopyrightCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...