MANILA — The global health community is trying to fast-track the development of a vaccine against the novel coronavirus. COVID-19 has now affected over 70 countries globally, with 93,090 confirmed cases and 3,198 deaths.
Questions are also emerging on global access to the vaccine, once a viable candidate has been developed.
“Governments have not developed a global governance framework for the equitable availability of vaccines for non-influenza virus outbreaks.”— David Fidler, adjunct senior fellow for cybersecurity and global health, Council on Foreign Relations
“At the moment, we have no access to a vaccine anywhere — an equity that makes no one comfortable,” David Fidler, adjunct senior fellow for cybersecurity and global health at the Council on Foreign Relations, told Devex.
When a vaccine will be developed, and who will have access to it are questions global health experts are grappling with, while looking for answers from lessons learned — or not learned — from past outbreaks.
Learning from past outbreaks
In a Facebook Live session last week, Lawrence Gostin, O’Neill Institute for National and Global Health Law professor and global health law expert, said past outbreaks have shown how higher-income countries such as the United States tend to hoard vaccine supplies to ensure supply for domestic demand.
Gostin said when he was part of a World Health Organization committee looking at equitable access to the vaccine against H1N1 in 2009, high-income countries, including the U.S., promised to share the vaccine with other countries. But when issues with vaccine production led to delays and shortages, the U.S. held off from fulfilling its pledge.
“We need equitable distribution both in the U.S. and globally. And we need to figure out a fair way to do it, and for me the fairest way is not through the basis of power and wealth, but by basis of need,” he said.
A needs-basis approach can be challenging too, said Michael Stoto, professor of health systems administration and population health at Georgetown University. For instance during the H1N1 pandemic, while children were at risk, they were less likely to suffer the consequences than older people, Stoto said.
“We really need to understand the epidemiology better to decide that if the vaccine is limited in the U.S., what part of the population is most likely to benefit from the vaccine,” Stoto said.
A global framework for equitable access
The international community to date has not arrived at a framework to address the problem of equitable vaccine access, particularly for low-income countries during a serious global health threat, CFR’s Fidler said.
He said vaccine access issues during the H5N1 and H1N1 pandemics were discussed in the negotiations for the Pandemic Influenza Preparedness Framework, known as the PIP Framework, which was adopted by the World Health Assembly in 2011. However, “doubts exist” whether the PIP Framework would help low-income countries access vaccines during a serious influenza pandemic, he said, adding that COVID-19 is not an influenza virus, and thus falls outside of the PIP Framework.
The Ebola vaccine situation is also incomparable to the current situation with COVID-19, as Ebola only posed a serious threat to a handful of countries, and so demand for the Ebola vaccine does not pose any access crisis globally.
Unlike Ebola, a vaccine for COVID-19 will likely have bigger demand given its international spread.
“Governments have not developed a global governance framework for the equitable availability of vaccines for non-influenza virus outbreaks,” Fidler said. “If the COVID-19 outbreak gets worse and endures with serious morbidity and mortality until an effective and safe vaccine is developed, we could well have an access crisis because high-income countries would be under enormous political pressure to use vaccine made [in] their territories for their own populations,” Fidler said.
Trials for a cure
There are over 70 therapeutic products currently identified by WHO in trials for COVID-19, or in clinical development for other coronaviruses. Some have never been approved for any specific disease, such as Gilead Sciences’ antiviral drug remdesivir. Bruce Aylward, leader of the WHO-China joint mission, said it is the only drug that seems to show real efficacy against COVID-19 at the moment.
Others in trial are drugs that could be repurposed, such as chloroquine, a medication used to treat and prevent malaria; and a combination of drugs used for HIV infections.
Alex Kong, researcher for the Access to Medicine Index of the Access to Medicine Foundation responsible for tracking companies' research and development pipelines, said it’s positive to see companies such as Gilead and AbbVie explore medicines that can be repurposed for COVID-19, as such medicines have already been tested for safety in humans and will take significantly less time to move from pipeline to market.
Governments are also more likely to allow trials for medicines already in use or under investigation. In addition, there’s already manufacturing capacity and supply chains in place for these medicines.
“With this type of medicine in particular, and a global outbreak, the access barriers we worry most about are supply shortages and stockouts, as well as the affordability of these medicines, especially when national governments have to find space in already limited budgets to procure these treatments. This is most concerning for low- and middle-income countries,” he told Devex.
But first, a vaccine
Whether there will be an access crisis depends on what happens with the outbreak in the next few months. If the outbreak continues, but proves to be less lethal, then fear and political pressure will dissipate, Fidler said, making any developed vaccine useful but not as critical.
But most importantly, it depends first and foremost on the development of a viable vaccine against COVID-19.
There are 27 candidate vaccines for COVID-19, as of the latest list identified by WHO. All of them have yet to undergo clinical trials, although some are expected to go into phase 1 clinical trials soon.
Moderna’s mRNA-1273 vaccine is seen as a frontrunner. It has already sent vials of its candidate vaccine to the National Institute of Allergy and Infectious Diseases in the U.S., and NIAID expects to start phase-1 clinical trials in April.
“The path for vaccine development can be full of sudden obstacles or issues that were not envisaged at the beginning.”— Marco Cavaleri, chair of the expert working group convened by WHO to advise on vaccine prioritization for COVID-19
Normally, vaccine development to approval takes up to 15 years, according to a Gavi, the Vaccine Alliance spokesperson. But the type of technology used to develop a vaccine against COVID-19, and the kind of safety and efficacy data available could potentially help speed up this timeline.
Coronavirus by region:
While there are still a number of unknowns in the outbreak, the spokesperson said that “given unprecedented levels of data/biological sample sharing and global collaboration, with a full-scale push, we could potentially have a COVID-19 vaccine — at least an investigational one for use in outbreaks — within two years.”
However, the spokesperson said this would require a “smooth process where every step is optimized in terms of speed, resources, and outcomes.”
“When a licensed vaccine is available, Gavi will work with its partners to ensure it is made accessible to those that need it the most,” the spokesperson said.
Dr. Jerome Kim, director general of the International Vaccine Institute, an international organization based in Seoul, South Korea, said a number of factors have so far helped in the speed of vaccine development for COVID-19.
These include the existence of the Coalition for Epidemic Preparedness Innovations, which in the current outbreak put out an early open call for proposals to accelerate vaccine development. Another is the existence of platform technologies that have been developed over the years, which could make it possible for multiple vaccines to be rapidly produced from a single system.
A DNA or RNA vaccine uses the genetic material of a virus or bacteria to stimulate the immune system, whereas traditional vaccines are made of whole bacteria or viruses, or a part of the bacteria or virus, such as a protein.
“Designing the new vaccine can be done very quickly within hours, sometimes, of obtaining the sequence. Making the DNA in the lab very quickly you can then inject it into an animal, a mouse, typically — and you may get a response typically, within 7 to 14 days after one or two doses (or longer depending on the timing of the second dose),” Kim told Devex in an email.
He said DNA and RNA can be made in large quantities, and once it has shown proper response in animals, one can move quickly to testing larger animals, monkeys, or to humans. In the U.S., DNA vaccines are no longer required to be tested in preclinical toxicology studies — a process where the vaccine is given to animals — often rabbits — for monitoring ill effects.
But a regulatory agency can also impose certain safety checks for vaccines being tested in humans for the first time, which can slow down enrolment in a study.
But it’s “very difficult” to nail down an exact timeline for when a viable vaccine against COVID-19 will be available for deployment, Marco Cavaleri, head of the anti-infectives and vaccines in the human medicines evaluation division at the European Medicines Agency and chair of the expert working group convened by WHO to advise on vaccine prioritization for COVID-19, told Devex. He said six months, and even 12-18 months are optimistic timelines.
It has been challenging to provide recommendations on what of the different vaccine candidates be given priority at this stage, given the limited information available, he said. All are still in preclinical trials.
“The path for vaccine development can be full of sudden obstacles or issues that were not envisaged at the beginning. So we have to be prepared that maybe it can take longer than that. … I do believe that 12, 18 months is a reasonable timeframe for the time being,” he said.
“Of course we are in an emergency setting, and the emergency setting affects [the different] considerations around the vaccines. There might be some inclination towards accepting a bit more risk than average,” he said.
Safety is of course a priority, and he said aspects related to vaccine safety in preclinical and clinical studies could also have an impact on the timeline of vaccine development.
Asked whether the panel has started, or is considering, discussions on potential market and access issues that’s likely to arise once a vaccine is developed, Cavaleri said this has been repeatedly discussed at WHO.
“It's pretty clear that availability and access are key elements that will have to be considered when thinking about which vaccine to prioritize,” he said.