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Experimental Ebola Vaccines

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    Over the last decade, the medical community has worked on vaccines geared towards stemming the Ebola virus. As of 2015, however, none has been green-lighted for use among humans stricken by the disease. Still, a variety of trial vaccines—such as replication-competent vesicular stomatitis (VSV) and replication-deficient adenovirus vectors—have shown promise in the testing stage, where they've managed to ward off infection among nonhuman subjects. This sample health essay explores these experimental vaccines and Ebola's history.

    Ebola Vaccine Research: Urgency in light of the recent outbreak

    In March 2014, the most rapid and deadly outbreak of the Ebola virus occurred in the West African nations of Guinea, Liberia, and Sierra Leone. The outbreak caught the world's scientific community off guard, and the issue has spurred controversy over how to treat such an epidemic in lieu of a known cure. For viruses as deadly as Ebola, the FDA has instituted the "Animal Efficacy Rule," whereby select approval is granted for vaccines that show promising results when tested on nonhuman primates.

    In light of recent Ebola outbreak in the U.S., some have argued that experimental drugs should be made available throughout the affected areas, while others insist that this would be risky and unethical. By Aug. 2014, the World Health Organization (WHO) seriously considered the use of unproven treatments as a stopgap measure until a verified cure could be found for the virus.

    Experimental ebola vaccines

    In an ongoing effort to conquer the 2014 disease outbreak, the United States reacted to the outbreak by creating new policies, and the World Community Grid has launched Outsmart Ebola Together, a global computing project aimed at finding chemicals that could be used for vaccines. Various biotechs are also working diligently to develop a cure, including Bavarian Nordic, Emergent BioSolutions, GlaxoSmithKline, Johnson & Johnson, and NewLink Genetics. As of Feb. 2015, laboratories throughout the world are running tests on possible Ebola vaccines, including the following prospects:

    Advac/MVA-BN

    Developed by Johnson & Johnson, this combines the vaccine elements of Crucell Holland B.V.'s AdVac and Bavarian Nordic's MVA-BN. In Jan. 2015, the vaccine entered its first trial phase at Oxford's Jenner Institute.

    BCX4430

    Conceived by BioCryst Pharmaceuticals, the drug has shown promise as a possible Ebola vaccine due to positive results on animals, despite arguments regarding the rights of animals versus the right to medical treatment. Funded by the U.S. National Institutes of Health, it was approved for a trial phase just before Christmas.

    Brincidofovir

    Though approved for emergency use by the FDA due to promising in vitro test results, a Jan. 2015 trial of the drug was halted in Liberia when no suitable volunteers came forth.

    cAd3-EBO Z

    NIAID, in partnership with Okairos, developed this vaccine from cAd3, a chimpanzee adenovirus. In Sept. 2014, it was administered to a trial group of 20 subjects in Bethesda, Md., and another 60 subjects at the University of Oxford. As of November, the general prognosis was good, with the subjects exhibiting Ebola antibodies in test results. By December, Oxford doctors were enrolling additional subjects to test a booster vaccine that Bavarian Nordic developed through MVA-BN ("Ebola Vaccine Clinical Development Overview").

    EBOV GP

    In Oct. 2014, Novavax Inc. announced its development of an anti-Ebola formula at the 8th Vaccine and ISV Conference. Preclinical studies found that the vaccine—based on the gene sequence of last year's Guinea outbreak—can boost the immune system from 10 to 100 percent. At last report, the company was preparing to follow its primate testing with a Phase 1 trial ("Novavax Announces Ebola Vaccine").

    Favipiravir (Avigan)

    Developed in Japan, the anti-influenza drug has also demonstrated promising results in an anti-Ebola mice model. Based on those tests, the drug was green-lighted for trial usage in Guéckédou, Guinea in the final weeks of 2014.

    JK-05

    Developed in China by Sihuan Pharmaceutical, the vaccination has shown impressive mouse model results on Ebola and various other infections. It has since been approved by that nation's authorities as a protective vaccine for local workers who are part of the relief efforts in Africa, where preliminary trials are set to begin.

    Nasal vaccine

    Last year, researchers at the University of Texas-Austin disclosed the results of an EVD vaccine that they'd been developing since the late noughties. When sprayed on a group of test monkeys, the remedial qualities of the vaccine were 100 percent effective. When monkeys were injected with the vaccine, Ebola was prevented in half of them. By Nov. 2014, however, the research team was having trouble procuring the funds necessary to expand their tests to human subjects (Stanton).

    Vaxart tablet

    Bay Area-based biotech Vaxart Inc. has developed a temperature-stable vaccine in the form of a tablet. In Jan. 2014, the team was earmarked with funds to bring their vaccine to the trial phase.

    VSV-EBOV

    The Public Health Agency of Canada and Merck Inc. have contributed to this vaccine, which is based on vesicular stomatitis virus. Oct. 2014 witnessed trials of the drug in four nations; these were briefly stopped in December due to purported side effects, but have since resumed. If the vaccine works in human volunteers like it has in animals, it could eventually be used to vaccinate West African residents against Ebola.

    ZMAb

    In a pre-breakout Nov. 2013 study, the drug boosted the immunities of infected macaque monkeys (one of the species threatened by ebola and other disease). Survival rates were excellent among those treated within a day of infection and very good for those administered the drug up to three months after exposure.

    ZMapp

    Developed through a series of tests carried on guinea pigs at U.S. and Canadian labs, the drug was green-lighted for limited human use after testing well on rhesus monkeys. Though success has thus far been minimal, the U.S. government has called for increased production of the drug, which has been funded generously by the Bill and Melinda Gates Foundation.

    According to estimates by Credit Suisse, the U.S. will earmark at least $1 billion towards the development of Ebola vaccines (Rooney).

    Existing drugs that could cure Ebola

    Questions have arisen as to whether certain pre-existing drugs could work to combat the Ebola virus, including drugs used to treat sexually transmitted diseases. At Manhattan's Icahn School of Medicine at Mount Sinai, researchers have pinpointed 53 such candidates (McNamee). Clomiphene and toremifene—both estrogen receptor modulators—were identified as potential Ebola inhibitors after stemming the virus in a mouse model. Amiodarone, dronedarone, and verapamil—all ion channel blockers—have also been found to stop the virus from penetrating the cells; the first of those, however, has already been dangerously overused at a Sierra Leone treatment clinic.

    According to WHO, Ebola could most effectively be remedied through transfusions of blood or purified serum from survivors. Previously, eight patients had been treated with this method during a 1996 Congo outbreak; hardly enough to verify the method's efficacy. In Dec. 2014, however, 70 patients participated in a clinical trial of this method in Liberia (Butler). With backing from the Gates Foundation, the method is set for further trials in Guinea and Sierra Leone.

    Lamivudine looks positive

    One drug that has shown a significant reduction in EBOV mortality, at least in a controlled setting, is lamivudine. While primarily used to treat HIV, the drug has been administered to Ebola patients at a Tubmanburg, Liberia clinic, where Dr. Gobee Logan has given lamivudine to 15 infected subjects, 13 of whom have survived. Statistically, that's a seven percent mortality rate, a huge drop from the 70 percent death rate among the Ebola population at large (Saul).

    Logan's use of the HIV drug stemmed from an urgent act of brainstorming; the doctor has noted how Ebola and the AIDS-causing virus work through the body in a similar way. "Ebola is a brainchild of HIV," he remarked to The Independent (Saul). The two patients that did succumb were treated more than a week after their initial exposure to the virus, whereas the remaining 13 were all treated within five days of infection.

    In response to Logan's success at stemming Ebola at his clinic, University of Reading virologist Dr. Benjamin Neuman reckoned that lamivudine has worked by tricking the virus at a molecular level, much like it has done with HIV. Still, Neuman insists that the drug will need to be tested on a larger number of patients before its effectiveness can really be determined (Saul).

    Additional Reading: HIV and current treatments

    Thailands efforts

    At Thailand's Siriraj Hospital, researchers have developed an antibody that they claim would thwart Ebola's ability to replicate. The vaccine is based on synthesized strands of the virus, which the team could only study via computer modeling due to a lack of overseas facilities. Still, the innovation has been encouraged by WHO and the U.S. National Institutes of Health, which have offered to help bring the vaccine to the testing stage.

    It remains to be seen whether a drug will emerge to eradicate Ebola. In any case, the sporadically recurring virus—which first surfaced in a 1976 Sudanese outbreak—is deadlier than ever, and the need for a cure has never been more urgent than it is today.

    Works Cited

    "Ebola Vaccine Clinical Development Overview." Who.int. World Health Organization. n.d. Web. 6 Feb. 2015.

    "Novavax Announces Ebola Vaccine Development Program at the 8th Vaccine and ISV Conference in Philadelphia." Nasdaq Global Newswire. NASDAQ OMX Group. 27 Oct. 2014. Web. 6 Feb. 2015.

    Stanton, Dan. "Ebola nasal vaccine under threat as funding runs dry". in-Pharma Technologist.com. William Reed Business Media. 12 Nov. 2014. Web. 6 Feb. 2015.

    Rooney, Ben. "Ebola: The making of a $1 billion drug." CNN Money. Cable News Network. 28 Oct. 2014. Web. 6 Feb. 2015.

    McNamee, David. "53 Ebola-blocking drugs identified among existing medications." MNT. MediLexicon International Ltd. 8 Dec. 2014. Web. 6 Feb. 2015.

    Butler, Declan. "First trials of blood-based Ebola therapy kick off". Nature. Nature Publishing Group. 15 Dec. 2014. Web. 6 Feb. 2015.

    Saul, Heather. "Ebola virus outbreak: Liberia doctor treating patients with HIV drugs report success". The Independent. n.p. 27 Sept. 2014. Web. 6 Feb. 2015.

     
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