Lessons from Ebola: A vaccine fast track too slow demonstrates need to prepare for pandemic potential diseases

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OneHealthThe following is a guest post by Elizabeth Bukowski, who covered the 3rd International One Health Congress in Amsterdam for Science Speaks. The conference, from March 18-21, focused on how science can help prevent emerging infectious diseases, 75 percent of which are estimated to originate in animals. The One Health concept recognizes that human, animal and environmental health are inextricably linked, as seen during recent outbreaks of Ebola.

Dr BukowskiAMSTERDAM – A fast-tracked Ebola vaccine candidate may have arrived in West Africa only after the deadliest days of the outbreak were over, but the development process has valuable lessons for other outbreaks of emerging diseases, said Professor Adrian Hill, director of the Jenner Institute at Oxford University, at the 3rd International One Health Congress in the Netherlands last week.

In August 2014, the World Health Organization declared the Ebola outbreak in West Africa a public health emergency and recommended accelerated clinical trials of two candidate vaccines for the disease. The mission was to “accomplish, within a matter of months, work that normally takes from two to four years, without compromising international standards for safety and efficacy,” according to a WHO statement.

Prof. Hill is leading some of the safety trials of one of the vaccine candidates, ChAd3 EBOZ, which was co-developed by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases. Phase I safety trials were performed last fall by the Jenner Institute in Oxford and Mali as well as by the NIAID in Maryland. Phase 2/3 testing for safety as well as efficacy began last month in Liberia.

The vaccine uses a chimpanzee cold virus vector to stimulate an immune response and carries DNA for a single protein in the Zaire strain of the virus, which is responsible for the current outbreak. Preclinical studies by NIAID showed it was well tolerated and led to excellent protection from the disease in macaques.

The second fast-tracked vaccine candidate, rVSV-ZEBOV, has also started efficacy testing in West Africa. Developed by NewLink Genetics, Merck Vaccines and the Public Health Agency of Canada, it uses a recombinant livestock virus called Vesicular Stomatitis Virus to stimulate the immune system. Other experimental vaccines are in earlier stages of development.

The collaborative, multi-trial approach to development of an Ebola vaccine is designed to identify the most effective vaccine and deliver it to vulnerable people as quickly as possible.

The Jenner Institute, which was created in 2005 to develop vaccines against global diseases, has conducted many vaccine trials, but the one for ChAd3 EBOZ was a little different. People in the Oxford community, eager to help ease the suffering in West Africa, quickly stepped forward to receive the experimental injection. The researchers had enough volunteers for the safety phase of testing without even advertising, Professor Hill said.

And then there was the rapid grant and regulatory process. The £2.8 million grant from the Wellcome Trust, Medical Research Council and UK Department for International Development was approved in two weeks. Ethical and regulatory approvals arrived in a matter of days.

The initial results, published in the New England Journal of Medicine in January , showed the vaccine was safe, but the immune response in people was weaker than in the macaque studies. While the level of antibodies and immune cells needed for protection in people is unknown, a higher vaccine dose is being used in the trials in Liberia in an effort to trigger a stronger response. And Prof. Hill will soon begin safety testing of a booster vaccine designed to amplify the immune response to ChAd3-EBOZ.

Of course, the situation in West Africa has changed dramatically since WHO moved to expedite the vaccines last August. Liberia reported its first Ebola case in weeks on Friday, and Sierra Leone was down to 55 new cases in the week ending March 15, the country’s lowest tally since June 2014, according to WHO reports. However, during the same week, Guinea saw 95 new cases, its highest in 2015. The crisis isn’t over, but scientists worry that virus exposure might be too spotty to provide trustworthy Phase 3 data on the vaccine’s ability to prevent infections.

In the meantime Prof. Hill hopes lessons from Ebola can be applied to other diseases. Looking at a list of 15 emerging diseases with pandemic potential—from SARS and Nipah virus to Marburg and Lassa Fever—he noted that none had a human vaccine ready.

Rapid clinical trial responses to outbreaks are possible, as shown by the delivery of experimental Ebola vaccines to West Africa in a fraction of the usual turnaround time. But they may not be rapid enough to effectively safeguard global health.

Advance preparation of vaccines is a better strategy than scrambling to respond to an outbreak already underway, Prof. Hill argues.  Vaccines for diseases with pandemic potential should be prepared and tested for safety now, before an outbreak occurs. Experimental vaccine candidates could then be stockpiled in at-risk regions so that clinical trials and potentially life-saving immunizations could be launched without delay in the event of an outbreak.

Unfortunately, major pharmaceutical companies have little financial incentive to adopt such an approach, Prof. Hill noted. Outbreaks of these emerging diseases are unpredictable, often short-lived and generally occur in low-income countries.

Yet the ongoing Ebola outbreak has demonstrated the high price of being caught unprepared. In addition to more than 10,000 lives lost and vast human suffering, the outbreak is estimated by the World Bank to cost West African economies $3-4 billion in 2015. Many vaccines could be prepared for that sum, Prof. Hill said.

He called for the creation of public-private partnerships to invest in development of vaccines for emerging diseases. Using common platforms could streamline production and reduce the cost of making seed lots and stockpiles. Enhancement of manufacturing infrastructure is needed so that vaccine production can be rapidly scaled up once an outbreak is identified, he noted.

Dr. Elizabeth Bukowski is a freelance journalist and Philadelphia-based veterinarian. Her work has appeared in the Wall Street Journal, Salon and other publications.


One thought on “Lessons from Ebola: A vaccine fast track too slow demonstrates need to prepare for pandemic potential diseases

  1. David Fedson

    Foreign physicians with severe Ebola virus disease (EVD) who were evacuated from West Africa to the US and Germany experienced diarrhea, vomiting, intravascular volume depletion and severe electrolyte abnormalities. These external and internal fluid losses were due to a breakdown of vascular integrity, but the patients survived with intensive supportive care. In contrast, almost all EVD patients in West Africa have received much more limited care,and mortality rates have been high. The chances of survival could be improved by treatment that restores vascular homeostasis, thus reducing EVD-associated fluid and electrolyte losses. Statins and angiotensin receptor blockers are known to restore vascular barrier integrity. In Sierra Leone, approximately 100 EVD patients were treated with a combination of these inexpensive and widely available generic agents. Survival was dramatically improved. Unfortunately, the physicians who treated these patients have refused to release their findings, and Ebola scientists and the World Health Organization remain interested only in clinical trials of treatments that target the virus, not agents that improve the host response to the disease. The Ebola outbreak may be winding down, but the virus will eventually return. Will we be better able to deal with it when it does?


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