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Ebola Vaccination: If Not Now, When?Ebola Vaccination: If Not Now, When? FREE

Alison P. Galvani, PhD; Martial L. Ndeffo-Mbah, PhD; Natasha Wenzel, MPH; and James E. Childs, PhD
[+] Article, Author, and Disclosure Information

This article was published online first at www.annals.org on 21 August 2014.


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.

Requests for Single Reprints: 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.galvani@yale.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.


Ann Intern Med. 2014;161(10):749-750. doi:10.7326/M14-1904
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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 Jump PlaceholderTable. Viable Ebola Vaccine Candidates 

Possible 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.

References

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:S76-86.
PubMed
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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:S430-7.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 

Figures

Tables

Table Jump PlaceholderTable. Viable Ebola Vaccine Candidates 

References

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:S76-86.
PubMed
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 
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:S430-7.
PubMed
CrossRef
 
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.
PubMed
CrossRef
 

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