Overview of Ebola and Marburg

Ebola Hemorrhagic Fever (EHF) and the related disease Marburg Virus Disease (MVD) are highly contagious, extremely deadly diseases that, if not contained by quarantine, are capable of threatening populations worldwide. Since 1976, when Ebola was first discovered, at least 28 outbreaks have occurred. The recent Ebola outbreak in West Africa is significantly larger than any previous epidemic, the first to reach urban areas and the first to lead to person-to-person transmission in the United States. As of February 2015, the current epidemic has resulted in over 22,500 infections with over 9,000 deaths (40% fatality rate). No approved preventive or therapeutic products exist for EHF or MVD.

Ebola and Marburg naturally infect animals including bats, creating reservoirs of Ebola and Marburg that, like rabies, cannot be completely eradicated. The rapid urbanization of many areas of Sub-Saharan Africa and the ease of modern air travel create conditions that facilitate the epidemic spread of EHF and MVD, which previously had been limited to localized outbreaks in villages. EHF is caused by ebolaviruses (Ebola), and MVD is caused by marburgviruses (Marburg). Ebola and Marburg are members of the family Filoviridae. Ebolaviruses are more diverse than marburgviruses and are divided into five subtypes: Zaire, Sudan, Bundibugyo, Tai Forest, and Reston. Zaire is the most lethal of the strains and is responsible for the current epidemic. Sudan and Bundibugyo are also lethal but have caused fewer and less severe outbreaks.

A challenge in Ebola and Marburg vaccine development is the need to create products that are effective both in containing an epidemic (in which rapid responses are critical) and in routine immunization (in which the duration of immunity is important). Ideal countermeasures to Ebola and Marburg would include a single-shot strain-specific epidemic vaccine capable of rapidly producing protective antibodies and T cells, and a routine vaccine capable of eliciting durable immunity to the lethal strains of Ebola (Zaire, Sudan and Bundibugyo) as well as Marburg. An effective vaccine against Ebola and/or Marburg would dramatically reduce the epidemic spread of infections as well as the transmission of Ebola and/or Marburg from natural animal hosts to humans.

Research on Ebola vaccines is progressing rapidly amongst a number of different pharmaceutical companies, with recombinant chimpanzee adenovirus (ChAd3), rare-serotype adenovirus (Ad26) and vesicular stomatitis virus (VSV) candidates already in clinical trials and several other vaccines scheduled to begin clinical trials. However, none of these vaccines has an ideal design, nor are any of them well suited for use in proactive immunization of populations to prevent future epidemics. The adenovirus vaccines require boosting with MVA to raise protective immune responses, and the two-product regimen (adenovirus and MVA) dramatically raises manufacturing costs and the complexity of vaccination. The replication competent VSV recombinants have already shown risk signals in the current trial, necessitating a temporary halt to the trial followed by resumption at a lower vaccine dose. The potential dose-limiting toxicity of the VSV vaccines raises safety concerns for large-scale vaccinations and also could pose threats to immunocompromised people, such as those infected with HIV. None of the competitors' vaccines produce virus-like particles, a desirable characteristic, which is discussed in detail elsewhere in this document. To the best of our knowledge, no non-GeoVax vaccine candidates share this characteristic. One or more of the current candidates may well show success in stemming the current epidemic. However, the world must be prepared with the optimal vaccine for the next epidemic when it occurs. All of the vaccines currently in clinical trials are designed to protect against one, or at most two, strains of Ebola. To be successful, an optimal vaccine should be safe, effective, and long lasting, all at a reasonable cost. Our analysis suggests that the GeoVax designs are well-suited to achieve this aim.