COVID-19, Shared knowledge and experiences regarding COVID-19
- August 6, 2020
The 12–18 month timeline that everyone quotes is actually based on a lot of data and experience. It’s also well founded because the last time the entire world summoned the scientific and medical community to make an accelerated vaccine in response to a global pandemic, they delivered a deployable vaccine within 12 months.
The 2014 Ebola outbreak was a historically devastating outbreak and by March, the number of cases and locations were beyond anything historically seen. Given the fragile public health infrastructure of West Africa, this was immediately declared a public health crisis and teams from the MSF (better known as Doctors Without Borders) and the CDC were immediately deployed. The WHO wouldn’t declare a pandemic until August 2014 but by then several thousands of people would have died, an important mistake that the WHO would correct for COVID-19. The below chart shows a relatively timeline of how the cases peaked relative to various events.
There is a good overview covered in The inside story of how scientists produced an Ebola vaccine. I highly recommend giving that a read as a supplement to this answer.
Despite the delayed declaration of the pandemic by the WHO, they started early calls for vaccines and therapeutics. Companies and labs from around the world reached into their libraries. One of the first to response was a small biotech company called NewLink which was working on an experimental Ebola vaccine based on a proof of concept recombinant vesicular stomatitis virus (rVSV) technology from the National Microbiology Laboratory in Winnipeg. The concept was demonstrated in monkeys back in 2005 but the group never had a serious scenario that required scaling up and the vaccine was sold to a tiny company called NewLink Genetics.  The Canadian team reached out to the WHO in April 2014 and were politely declined. But when the pandemic was declared, MSF asked for immediate development of the a vaccine and the rVSV-ZEBOV vaccine was one of the first selected.
Due to the controversial nature of field testing new drugs in developing countries like those in Africa, the NIH and the Walter Reed Army Institute of Research with funding from BARDA would team up with NewLink to start Phase I safety trials in the US. They started shopping the vaccine around to a larger vaccine manufacturer and Merck stepped in. Interestingly, GSK would pilot its cAd3 platform with the NIAID and JnJ and its Ad26.ZEBOV platform both which are currently being tested for COVID-19. Merck’s familiarity with the vector manufacturing process allowed them to rapidly start the process scaleup for the vaccine and would formally step into the process November 2014, 3 months after the initial call from BARDA and the WHO.
Thus began the global effort to test and scale the vaccine. In clinical trials held around the globe, the rVSV-ZEBOV vaccine was tested in 8 independent Phase I dosing trials.
One of the major bioethics questions was how to deploy the vaccine in the area that needed it the most. Guinea volunteered to host the trial but the country largely lacked the healthcare infrastructure to host an traditional randomized controlled trial. What was proposed was to use a ring vaccination design where anyone who had direct contact with an Ebola patient would be immediately vaccinated and all of those who had contact with those people would also be vaccinated. As a control, certain populations would get the vaccine 21 days later. This design had a balance between risk vs. benefit.
The Ebola This is Enough Phase III trial was run from April 15 – July 20, 2015 vaccinating 7651 patients. Ebola symptoms typically show up 10 days after exposure and it was shown that the groups that got the vaccine immediately had a far lower number of cases than the groups that got the vaccine 21-days later.
Based on the data from this study on July 24, 2015, the government of Guinea recommended the full use of rVSV-ZEBOV in immediate vaccination of new clusters of Ebola. This recommendation came at an unprecedented timeline of less than 12 months from the initial call for the development of a vaccine.
The rVSV-ZEBOV vaccine wouldn’t be approved immediately. By the summer of 2015, Ebola cases subsided and other vaccine efforts including cAd3-ZEBOV was never completed. But due to fears of reemergence, the WHO and other countries continued development of the vaccines along with other therapeutics. When the 2018 DRC and the 2018 Kivu outbreaks occurred, these vaccines were ready for deployment and the results of those trials ultimately resulted in the defeat of those outbreaks and the subsequent approval by the FDA and the EMA in what was a record setting 5 years from the start of human trials.
When Dr. Fauci tells everyone a vaccine may be ready in 12–18 months, he is talking from experience because he has seen it happened before. Since the Ebola outbreak, the Coalition for Epidemic Preparedness Innovations (CEPI) was started with funding from the Bill and Melinda Gates Foundation, the Wellcome Trust and several countries to take the lessons learned from the vaccine development efforts against Ebola and to organize initiatives to combat the next pandemic. If there was ever a time to make a vaccine within 12 months, the World is a lot more prepared for it than it was 10 years ago.
Footnotes Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial
Senior Engineer in Drug Manufacturing Science
Lives in Providence, RI2017–present
Lives in Providence, RI2017–present