Part 1 of 2
In 2014 and 2015, Ebola virus infection killed 8,698 people in Sierra Leone, 3,337 in Guinea and 3,955 in Liberia. There were survivors, but the death rate was very high, and the threat of a new epidemic lingers.
A traveler from west Africa brought the disease to Dallas, where a struggle to save him failed and accidentally infected two nurses. Both were moved to the National Institutes of Health and survived.
With the appearance of more cases in the United States and Europe, the press and the Congress achieved near hysteria; Dr. Anthony Fauci of the National Institute of Allergy and Infectious Disease and Dr. Tom Frieden of the Centers for Disease Control and Prevention were falsely accused of running failing agencies by members of Congress, of all ironies.
The West African Ebola epidemic was the largest on record. The response of the World Health Organization and other agencies was slow, allowing the disease to spread into urban areas. Many groups, including Médecins sans Frontières (Doctors Without Borders), were heroic, but absent a vaccine or an effective drug, all they could provide was basic medicine and apply public health measures such as quarantine and isolation.
The NIH, The Canadian Health Service, Merck and other organizations had potential vaccines, which had been successfully tested in macaques for protection against infection and in humans for immune responses, but none had been approved by the beginning of the epidemic. This column covered these vaccines at the time. See: /category/opinion-author/body-scientific.
These vaccine viruses have one carefully chosen gene from Ebola virus, and the rest of the virus has genetic material from another well-studied and harmless virus called VSV. The Ebola gene comes from the Zaire strain of Ebola Virus (ZEBOV). The hybrid virus, rVSV-ZEBOV, is a bit of Rube-Goldberg entity and grows just enough when injected into a muscle to provoke an immune response to Ebola virus. These antibodies protect macaques from subsequent infection. There is also a T-cell response, which the body uses to destroy cells in which the Ebola virus is made. The vaccine induces antibodies and T-cells in humans as well, but it would be unethical to infect humans with Ebola virus.
The affected countries and the World Health Organization were not prepared for the 2014–2015 epidemic. There was no agreement on which of several candidate vaccines should be used or how resources would be mobilized or financed for a new epidemic. There had not been enough coordination with local governments. Medical personnel did not understand that people in west Africa might reject their efforts to isolate them from sick or dead relatives. Critically, there was no consensus on the design of a clinical trial for the rVSV-ZEBOV vaccine.
A review in Science magazine on July 14, 2017, by Drs. Marc Lipsitch and Nir Eyal of the Harvard School of Public Health summarizes thinking since the 2014–2015 epidemic. Their message is that all planning for an outbreak of Ebola or any other infectious agent must be done in advance. Planning includes preparation of vaccines and testing them in primates and then in healthy human volunteers. Logistics for personnel, equipment and medications must be ready, so that an epidemic can be tackled early, when it will do the most good and there are many people to participate in clinical trials.
In response to the 2014–2015 Ebola epidemic response, The Coalition for Epidemic Preparedness Innovations (CEPI, pronounced “seppy”) was formed in January of 2017. The CEPI website states: “CEPI is a new alliance between governments, industry, academia, philanthropy, intergovernmental institutions, such as the World Health Organization, and civil society.
“We exist to finance and coordinate the development of new vaccines to prevent and contain infectious disease epidemics. As epidemics disproportionately affect low-income countries, CEPI will ensure that the vaccines we help to develop are affordable, so that price is never a barrier to access, and they are available to populations with the most need.”
CEPI’s founding members were the governments of Norway, Germany, Japan and India; The Wellcome Trust in the UK; The Bill and Melinda Gates Foundation; The World Economic Forum and The European Union. Angela Merkel and Bill Gates chaired the opening meeting.
For Ebola, many problems remain, including the design of clinical trials. Drs. Lipsitch and Eyal point out, with admirable understatement, that: “excellent trial design is a subtle and complex art.”
At the end of the last epidemic, as the number of cases was waning, a small clinical trial of the recombinant virus vaccine took place. The trial was named Ebola, Ça suffit! (Ebola, that’s enough!). What went into that clinical trial, the ethical problems it presented and the results will be the subject of the next column.
Richard Kessin is Professor of Pathology and Cell Biology Emeritus at Columbia University. He lives in Norfolk and can be reached at Richard.Kessin@gmail.com for original data or other matters.
