COMMENTARY

The Aftermath of Ebola: Are We Any Better Off?

Progress in Vaccines and Treatments

Julie T. Joseph, MD, MPH

Disclosures

December 07, 2015

Editor's Note: This article was based, in part, on an interview with Thomas Geisbert, PhD, by the author, Julie T. Joseph, MD, MPH.

Are We Better Prepared for Ebola?

One year after the first Ebola victim died hemorrhaging in Africa, what progress has been made toward preventing and curing one of the most highly infectious and fatal diseases seen this century? If someone became infected with Ebola today, are we any better off?

The high mortality and swift spread of the Ebola virus was seen in the 2014 outbreak, the deadliest since its discovery in 1976. It was also the largest in history, as measured by the death toll and by the number of countries it has affected.

Case counts by the World Health Organization (WHO) and the Centers for Diseases Control and Prevention (CDC) report that the 2014 Ebola epidemic caused 11,299 deaths and affected 10 countries: Liberia, Guinea, Sierra Leone, Nigeria, Senegal, Mali, Spain, Italy, the United Kingdom, and the United States.[1,2]

At the time of the Ebola epidemic, there was no vaccine to prevent contracting Ebola nor was any treatment available. It was not until the WHO declared Ebola an international emergency in August 2014 that decisive action was undertaken to advance Ebola research.[3] Until the most recent outbreak, there was little urgency to develop a vaccine because Ebola was so rare. In 2014, several vaccines that had only been tested in animals were quickly advanced into phase 1 clinical trials.

It's Not Just Ebola

"The outbreaks fast-tracked these vaccines to a point they can be used and tested in humans now," said Dr Thomas Geisbert, professor of microbiology and immunology at the University of Texas Medical Branch in Galveston, Texas. Dr Geisbert has a laboratory that focuses on the pathogenesis of emerging and re-emerging viruses that cause hemorrhagic fever, including the Ebola, Marburg, and Lassa viruses.

"I think we are better prepared now; however, what we really need is a multivalent vaccine to tackle not only Ebola but also Marburg and Lassa," said Geisbert.

No vaccine is yet available for Marburg and Lassa viruses, two rare but highly infectious and fatal emerging infectious diseases seen in West Africa. According to the CDC, the case-fatality rate for Marburg hemorrhagic fever ranges from 23% to 90%, and Lassa virus disease causes approximately 5000 deaths annually in West Africa.[4,5]

Ebola Vaccines in the Pipeline

Currently, four main Ebola vaccine trials are in progress. One vaccine, ChAd3-ZEBOV, has been developed by GlaxoSmithKline and the US National Institute of Allergy and Infectious Diseases. Another vaccine, VSV-EBOV, is produced by Merck Vaccines USA in collaboration with the Public Health Agency of Canada. The trial involving VSV-EBOV progressed to phase 3 recently in Guinea. The preliminary results of this trial show that the vaccine "might be highly efficacious and safe," but researchers admit that more data need to be collected in humans for conclusive evidence.[6,7]

The third vaccine, Ad26-EBOV and MVA-EBOV, is a two-dose vaccination developed by Johnson & Johnson in association with Bavarian Nordic. Novavax, a US biotech company, is working on the fourth vaccine. All four vaccines have proven to be safe in humans, but it is not clear yet whether they can actually protect against Ebola.

The Quest for Ebola Therapies

Aside from Ebola vaccine development, what efforts have been made to develop treatment for those already infected?

Two drugs, favipiravir and brincidofovir, are currently undergoing testing at the Medecins sans Frontieres facility in Geneva, Switzerland, an international, independent, medical humanitarian organization. Unfortunately, trial results show that favipiravir may only be useful in the early stages of the illness; it appears less likely to be helpful in individuals with advanced disease.[8] The trial on brincidofovir was stopped owing to a reduction in the number of patients infected with Ebola and available for the trial. Low patient recruitment has been a challenge for Ebola trials.[9]

ZMapp™ is another experimental drug developed by Mapp Biopharmaceuticals for the treatment of Ebola. However, as a result of the diminished number of new Ebola cases in West Africa, the ability to test Zmapp is limited, and clinical evidence of the drug's effectiveness is lacking.[6]

Dr Geisbert was involved in a study of the drug, TKM-Ebola-Makona, designed specifically to fight the strain of Ebola in the 2014 West African outbreak. His study was able to show the drug to be effective in monkeys.[10] However, as Dr Geisbert states, "The $64,000 question is: How do we successfully package this drug to work in humans with minimal side effects?"

"The development of Ebola vaccine and therapies has been a frustrating process," said Dr Geisbert. He attributes the complexity of developing a treatment for Ebola to the poor public health infrastructure in West Africa. "We can take our best drugs that work in monkeys, but they have a low chance of working in humans in whom the disease has already advanced, making it difficult to see whether the vaccine worked," said Dr Geisbert.

Despite the many confounding variables that make developing Ebola vaccines and drugs challenging, Dr Geisbert reiterated, "I think we are better prepared now to deal with an outbreak than we were a year ago."

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