Safety Testing of Ebola Vaccine Candidates Underway

The 2014 Ebola outbreak is the largest in history and is estimated to have caused 2,473 infections and more than 1,400 suspected and confirmed deaths in Guinea, Liberia, Nigeria, and Sierra Leone since March 2014, when the outbreak was first reported, according to the World Health Organization (WHO). The outbreak is the first in West Africa and the first to affect urban areas. In September, the Centers for Disease Control and Prevention warned that the number of Ebola cases in West Africa could reach 1.4 million by the end of January if trends continue without an immediate and massive scale-up in response. Researchers say the total number of cases is vastly underreported.

According to CDC Director Tom Frieden, this estimate does not reflect actions taken or planned since August by the United States and the international community, actions that, he notes, [the CDC] anticipates will slow the spread of the epidemic. He noted at press time that the epidemic could still be reversed if enough sick patients can be contained in medical facilities, Ebola treatment units, or in other facilities where the risk of transmission is reduced. Many hospitals are filled to capacity, and patients must be turned away from treatment centers that are also overcrowded.

The United States recently has committed to a $750 million initiative that would establish treatment facilities in Liberia, and the United Nations Security Council voted unanimously last week to create an emergency medical mission to respond to the outbreak, according to the CDC. In addition, the WHO is undertaking an effort to move infected people out of their homes and into small centers that would provide at least rudimentary levels of care.1

According to “FACT SHEET: U.S. Response to the Ebola Epidemic in West Africa,” President Obama has declared the Ebola epidemic in West Africa and the humanitarian crisis there “a top national security priority for the United States.” He said in an address to the American people in September that “the United States is partnering with the United Nations and other international partners to help the Governments of Guinea, Liberia, Sierra Leone, Nigeria, and Senegal respond just as we fortify our defenses at home.”

The U.S. military and broader uniformed services will engage in command and control, logistics expertise, training, and engineering support, the President advised. The United States will also do the following:

  • U.S. Africa Command will set up a Joint Force Command headquartered in Monrovia, Liberia, to provide regional command and control support to U.S. military activities and facilitate coordination with U.S. government and international relief efforts. A general from U.S. Army Africa, the Army component of U.S. Africa Command, will lead this effort, which will involve an estimated 3,000 U.S. forces.
  • U.S. Africa Command will establish a regional intermediate staging base (ISB) to facilitate and expedite the transportation of equipment, supplies and personnel. Of the U.S. forces taking part in this response, many will be stationed at the ISB.
  • Command engineers will build additional Ebola Treatment Units in affected areas, and the U.S. Government will help recruit and organize medical personnel to staff them.
  • The Command will establish a site to train up to 500 health care providers per week, enabling healthcare workers to safely provide direct medical care to patients.
  • The United States Public Health Service Commissioned Corps is preparing to deploy 65 Commissioned Corps officers to Liberia to manage and staff a previously announced Department of Defense (DoD) hospital to care for healthcare workers who become ill. The deployment roster will consist of administrators, clinicians, and support staff.
  • USAID is supporting a Community Care Campaign, which will provide communities and households with protection kits, appropriate information, and training on how to protect themselves and their loved ones. In partnership with the United Nations Children Fund, the Paul Allen Family Foundation, and other key partners, 400,000 of the most vulnerable households in Liberia will be targeted. The package will subsequently be scaled to cover the country and the broader region.
  • As part of this effort, this week, USAID will airlift 50,000 home health care kits from Denmark to Liberia to be hand-delivered to distant communities by trained youth volunteers.

The Fact Sheet lists numerous initiatives and precautionary programs the United States is undertaking.

Symptoms and Vaccines

There are no approved drugs for Ebola virus disease. Prompt diagnosis and aggressive supportive care can improve survival. The disease is characterized by high fever, headache, body aches, intense weakness, stomach pain, and lack of appetite. This is followed by vomiting, diarrhea, rash, impaired kidney and liver function, and in some cases, internal and external bleeding. The outbreak of Ebola in West Africa prompted the NIH to accelerate the pace of human safety testing for experimental Ebola vaccines.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH,) began human testing of an investigational vaccine to prevent Ebola virus disease in early September, according to an NIH press release.3 Participants in all trials are healthy adults who are not infected with Ebola virus.

EBOLA/MARBURG HEMORRHAGIC FEVERS

Ebola and Marburg hemorrhagic fevers are acute diseases that often lead to severe illness and death in both humans and nonhuman primates. The diseases typically affect multiple organs in the body and are often accompanied by hemorrhage (bleeding). The illnesses are caused by filoviruses, the only two known members of the virus family Filoviridae.

Marburg hemorrhagic fever was first recognized in 1967, when laboratory workers in Germany and Yugoslavia developed a hemorrhagic illness after handling tissue from green monkeys. The outbreak resulted in 31 infections and 7 deaths. Researchers later identified the cause as a never-before-seen filovirus, termed “Marburg” after one of the outbreak locations.

Eleven years later, Ebola virus was identified when two outbreaks of hemorrhagic fever occurred in northern Zaire (now the Democratic Republic of Congo) and southern Sudan. The causes of the outbreaks were identified as two different species of another novel filovirus, called “Ebola” after a river in northern Zaire. Both species proved to be highly lethal, as 90 percent of the Zairian cases and 50 percent of the Sudanese cases resulted in death.

Source: www.nih.gov

The following Phase 1 trials have been scheduled:

  • A vaccine co-developed by NIAID and GlaxoSmithKline (GSK) will be tested in Phase 1 trial VRC 207 at the NIH Clinical Center in Bethesda, Maryland.
  • The NIH, in collaboration with the U.S. Department of Defense, will support NewLink Genetics Corp., a biopharmaceutical company in Ames, Iowa, in conducting Phase 1 safety studies of the investigational recombinant vesicular stomatitis virus Ebola vaccine (VSV-EBOV) licensed from the Public Health Agency of Canada. Those clinical trials are expected to begin in the fall at the Clinical Trials Center of Walter Reed Army Institute of Research in Silver Spring, Maryland.
  • A British-based international consortium that includes the Wellcome Trust and Britain’s Medical Research Council and Department for International Development, with whom NIH has partnered, will test the NIAID/GSK vaccine candidate among healthy volunteers in the United Kingdom and in the West African countries of Gambia (after approval from the relevant authorities) and Mali.
  • The U.S. Centers for Disease Control and Prevention has been in discussions with Ministry of Health officials in Nigeria about the possibility of conducting a Phase 1 safety study of the vaccine among healthy adults in that country.

Initial safety and immunogenicity data from the Phase 1 trials of the NIAID/GSK investigational Ebola vaccine are expected in late 2014.

Clinical trials consist of three phases: Phase 1 is the first step. Researchers test an investigational vaccine in a small group of people to evaluate its safety and the immune response it provokes. Phase 2 clinical trials are designed to further assess safety and immune response in larger numbers of volunteers. In some cases, the vaccine’s ability to prevent infection or disease (called efficacy) can be determined in Phase 2. Phase 3 is directed predominantly at determining efficacy.

“Today we know the best way to prevent the spread of Ebola infection is through public health measures, including good infection-control practices, isolation, contact tracing, quarantine, and provision of personal protective equipment,” explains NIAID Director Anthony S. Fauci, M.D. “However, a vaccine will ultimately be an important tool in the prevention effort. The launch of Phase 1 Ebola vaccine studies is the first step in a long process.”

Animal-to-Human Transmission

Pardis Sabeti, MD, Ph.D., an NIH-sponsored researcher, compiled research that indicated that “a single animal to human transmission event is responsible for the 2014 Ebola outbreak.”4 Sabeti, senior associate member of the Broad Institute, Cambridge, Massachusetts, and her team used advanced genomic sequencing technology to identify a single point of infection from an animal reservoir to a human in the current outbreak in West Africa. They found that “the genetic code of the virus is changing over time to adapt to human hosts.”

The team sought to better understand why the West Africa outbreak is larger than previous outbreaks. They and an international team of scientists extensively analyzed the genetic makeup of Ebola samples from patients living in affected regions. They “pinpointed a single late 2013 introduction from an unspecified animal reservoir into humans,” according to the NIH. The study showed that the strain responsible for the West African outbreak had been part of a closely related strain found in Central Africa as early as 2004. It had moved from Central to West Africa over the span of a decade. Studying RNA changes that occurred over those years “suggests that the first human infection of the outbreak was followed by exclusive human-to-human transmissions,” according to the researchers.

The genetic makeup of the Ebola samples indicated that a number of mutations arose as the outbreak spread. Some of these mutations alter the biological state of the virus and may allow it to continually and rapidly adapt to human immune defenses as the outbreak continues. This finding indicates the need for improved methods of closely monitoring changes in the viral genome and the effects on vaccine targets, which can help scientists determine how the Ebola virus spreads and evolves and to better detect infection and develop more efficacious drugs and vaccines.

References:

1. http://www.washingtonpost.com/national/health-science/cdc-ebola-could-infect-14-million-in-west-africa-by-end-of-january-if-trends-continue/2014/09/23/fc260920-4317-11e4-9a15-137aa0153527_story.html?wpisrc=al_national.

2. http://www.whitehouse.gov/the-press-office/2014/09/16/fact-sheet-us-response-ebola-epidemic-west-africa.

3. http://www.nih.gov/news/health/aug2014/niaid-28.htm> Information on the Phase 1 clinical trials is at http://www.niaid.nih.gov/news/QA/Pages/EbolaVaxQA aspx.

4. http://www.nih.gov/news/health/aug2014/od-29.htm.

 

Mary Jane DittmarMARY JANE DITTMAR is senior associate editor of Fire Engineering and conference manager of FDIC. Before joining the magazine in January 1991, she served as editor of a trade magazine in the health/nutrition market and held various positions in the educational and medical advertising fields. She has a bachelor’s degree in English/journalism and a master’s degree in communication arts.

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