University of Oxford researchers began testing a COVID-19 vaccine in humans.
About 1,100 volunteers will take part in the trial. Half will receive the new coronavirus vaccine, and the other half (the control group) will get a licensed meningitis vaccine, according to the University of Oxford. On April 23, the first two volunteers were injected, one with the experimental vaccine and the other with the control.
The study aims to assess whether healthy people can be protected from COVID-19 with this new vaccine called ChAdOx1 nCoV-19. The vaccine is made from a virus (ChAdOx1), which is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees but which has been genetically altered so that it is impossible for it to grow in humans.
The Oxford study is the third vaccine, funded by the Coalition for Epidemic Preparedness Innovations, to enter into human trials, or Phase I, according to CEPI. There are only six vaccines in Phase I and five in Phase I-II. And there are 115 vaccine candidates in development, 78 confirmed as active, according to research by CEPI in “The COVID-19 Vaccine Landscape” in Nature Reviews Drug Discovery on April 9.
The first COVID-19 vaccine candidate entered human clinical testing on March 16.
Many vaccine candidates will not gain approval for human studies due to toxicity, ineffectiveness to induce immune responses or dosing failures in laboratory animals, or because they run out of money.
The probability of success for an infectious disease vaccine candidate to pass preclinical barriers and reach Phase I, which evaluates the safety of humans, is 41 percent to 57 percent based on four sources, according to “Estimating the cost of vaccine development against epidemic infectious diseases: a cost minimisation study;” in The Lancet Global, October 13, 2018.
Drugs in Phase II, when formulation and dosages are established to prove effectiveness, historically have experienced the lowest rate of success. In Phase III, the safety and efficacy need to be shown in a large group of people. Only 30.7 percent of developmental candidates advanced from Phase II to Phase III in a study of 7,456 trials from 2006-2015 across 1,103 countries, the largest study of its kind, according to “Clinical Development Success Rates 2006-2015” by the Biotechnology Innovation Organization, the world’s largest biotech trade group.
The process of developing a drug from preclinical research to marketing in the United States can take about 12 to 18 years and costs $1.2 billion, according to “Fixing a Broken Drug Development Process” in the Journal of Commercial Biotechnology (2013).
However, COVID-19 vaccine researchers are not starting from the beginning.
Past research on vaccines for SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome-related coronavirus) vaccines has identified potential approaches, according to the Mayo Clinic. Coronaviruses have a spike-like structure on their surface called an S protein. (The spikes create the corona-like, or crown-like, appearance that gives the viruses their name.) The S protein attaches to the surface of human cells. Most vaccines in development target this protein to prevent it from binding to human cells and stop the virus from reproducing.
“A striking feature of the vaccine development landscape for COVID-19 is the range of technology platforms being evaluated, including nucleic acid (DNA and RNA), virus-like particle, peptide, viral vector (replicating and non-replicating), recombinant protein, live attenuated virus and inactivated virus approaches. Many of these platforms are not currently the basis for licensed vaccines,” according to the article in Nature Reviews Drug Discovery, which could slow down vaccine approval.
Because of the seriousness of the COVID-19 pandemic, vaccine regulators also may fast-track some of the steps toward approval, said the Mayo Clinic.
“Realistically, a vaccine will take 12 to 18 months or longer to develop and test in human clinical trials,” reported the Mayo Clinic. “And we don’t know yet whether an effective vaccine is possible for this virus.”
If a vaccine is approved, it will take time to produce, distribute and administer to the global population. Because the novel coronavirus is new, it is likely that two vaccinations would be needed, three to four weeks apart, said the Mayo Clinic. People probably would achieve immunity to COVID-19 one to two weeks after the second vaccination.
Much work needs to be done. Many questions need answers. But the high number of vaccine candidates is hopeful.
Another reason for hope is that, before the new coronavirus, the organizational groundwork had been laid for vaccine development against emerging infectious diseases.
The Coalition for Epidemic Preparedness Innovations (CEPI) was launched in 2017 in reaction to the Ebola virus and a commitment to make vaccines affordable to developing nations. It funds and coordinates vaccine research projects.
CEPI, based in Oslo, Norway, has been described as a “key player” in the race to develop a vaccine for the new coronavirus in “The Road to a Coronavirus Vaccine Runs Through Oslo” in Bloomberg Businessweek, on February 13.
“Absolutely, without a doubt,” CEPI has accelerated development of a vaccine against the virus,” said Phyllis Arthur, vice president for infectious diseases and diagnostics policy at Biotechnology Innovation Organization, the biotech trade group.
Bloomberg Businessweek said that “CEPI solves what economists call a “coordination problem”. It can help pair boutique research and development companies with big vaccine manufacturers, work with regulators to streamline approval processes and resolve patent disputes on the spot. Its scientific advisory committee has executives from Pfizer, Johnson & Johnson, and Japan’s Takeda Pharmaceutical, among others.
CEPI was founded in Davos, Switzerland, by the governments of Norway and India, the Bill & Melinda Gates Foundation, Wellcome Trust and the World Economic Forum.
The coalition has secured financial investment from many governments, including Denmark, Ethiopia, Finland, Germany, Japan and Norway, as well as the Bill & Melinda Gates Foundation and the Wellcome Trust. The European Union also provides substantial financial contributions. Individuals, through the UN Foundation’s COVID-19 Solidarity Response Fund, and the private sector also have donated to CEPI.
How much will COVID-19 vaccine development cost?
US$2 billion, CEPI said. As of April 26, it has raised US$915 million.
The Netherlands pledged US$54.5 million and Switzerland US$103 million, CEPI said on April 16. Saudi Arabia pledged US$150 million, CEPI reported on April 21. The United Kingdom pledged £210 million toward work focused on a COVID-19 vaccine, making Britain CEPI’s largest donor, said the Independent on March 26. By February 2020, CEPI had raised US$760 with additional donations from Australia, Belgium and Canada.
The World Health Organization announced, on April 24, a global landmark collaboration to accelerate the development, production and equitable global access to new COVID-19 health technologies. The other collaborators were CEPI, the Bill & Melinda Gates Foundation, Gavi (the Vaccine Alliance), Global Fund, UNITAID, Wellcome Trust, private sector partners and other stakeholders.
A rolling pledge campaign will begin on May 4.
“We understand we cannot do this alone, and that we need to work together in unprecedented and inclusive partnership with all stakeholders – political leaders, public and private sectors, civil society, academia, and all other stakeholders across society – jointly leveraging our comparative strengths and respective voices to drive towards collective solutions, an accelerated path, and access for all. We are stronger, faster and more effective working together.”
Of the confirmed active vaccine candidates, 56 (72 percent) are being developed by private/industry developers, with the remaining 22 (28 percent) of projects being led by academic, public sector and other non-profit organizations, according to the article in Nature Reviews Drug Discovery.
Most COVID-19 vaccine development activity is in North America, with 36 (46 percent), compared with 14 (18 percent) in China, 14 (18 percent) in Australia and Asia, excluding China, and 14 (18 percent) in Europe.
However, there is currently no public information on vaccine development in Africa or Latin America, although vaccine manufacturing capacity and regulatory frameworks exist in these regions. The epidemiology of COVID-19 might differ by geography, and it is likely that effective control of the pandemic will require greater coordination and involvement of the Southern Hemisphere in vaccine research and development.