DETERMINED to save lives in a country with rising Coronavirus infections (5,621 confirmed cases and 176 deaths as at yesterday), President Muhammadu Buhari has directed appropriate agencies to embark on validation of an herbal mixture touted as cure for coronavirus. Although the World Health Organisation (WHO) has repeatedly said that it has not approved any drug or vaccine for treating coronavirus, many have hailed COVID-Organics from Madagascar as Africa’s response to the global pandemic that has no cure yet.
Nevertheless, the Madagascar’s herbal mixture has continued to dominate headlines, with Boss Mustapha, chairman of the Presidential Task Force on COVID-19, disclosing this week that the National Institute for Pharmaceutical Research and Development (NIPRD) and the National Agency for Food and Drug Administration and Control (NAFDAC) have been mandated to carry out clinical analysis of its efficacy before the herbal mixture could be allowed for treating patients in Nigeria.
WHO tracking 8 vaccines in clinical evaluation
Last week, WHO said it was tracking eight potential vaccines for COVID-19 in clinical evaluation. These candidate vaccines included four from China, one from England, two from the United States and one from the European Union. The list also includes 100 candidate vaccines in preclinical evaluation, which means they are still being tested in test tubes or in animals. The previous version of the list, published on April 20, included 5 candidate vaccines in clinical evaluation and 71 in preclinical evaluation.
Also last week, New York-based pharmaceutical giant Pfizer announced that it had begun testing a vaccine candidate for SARS-CoV-2, the virus that causes COVID-19. The company said it went from pre-clinical studies in test tubes and animals to injecting humans with a possible vaccine in less than four months. The trials, which are taking place in the United States, are still in phase one testing. These test whether a potential vaccine is safe, has side effects and produces the desired response from the body’s immune system. Vaccines must go through phase 1, 2 and 3 testing before they can be licensed. Each phase involves larger numbers of volunteers.
Pfizer said it is working with German pharmaceutical company BioNTech on the candidate vaccine, dubbed BNT162. The company first tested it in Germany last month on 12 healthy adults. The two companies say they plan to test the candidate vaccine on 360 healthy volunteers in the United States. BNT162 is a messenger RNA vaccine that instructs cells to make a specific piece of protein to match what’s on SARS-CoV-2’s spike protein. The hope is the protein pieces will cause the body to create antibodies that will stop the virus from being able to attach to and invade cells.
In the United States, the first SARS-CoV-2 trial vaccine has been cleared to go into phase two testing by the Food and Drug Administration. The vaccine candidate by Massachusetts-based Moderna, touted as a potential vaccine that could be used if found safe and effective, is called mRNA-1273. It was first given to volunteers in Seattle on March 16 during the phase one testing. Reports had it that FDA has completed its review of Moderna’s Investigational New Drug application for mRNA-1273, which allows it to now proceed to phase two testing.
The study, which will begin enrolling 600 participants in the coming weeks, is designed to begin assessing whether or not the potential vaccine can induce a person’s immune system to produce antibodies that recognise SARS-CoV-2. With the news, Moderna pulls neck and neck with the current coronavirus vaccine leader, Oxford University’s Jenner Institute. Scientists there had a head start. Having already acquired safety data from human trials of similar vaccines for the related coronavirus that causes MERS, Oxford researchers convinced British regulators to push forward with a large Phase II study involving 6,000 people while the outbreak in the UK is still raging. The vaccine is based on a technology that involves genetically modifying a harmless virus to create a SARS-CoV-2 look-alike that doesn’t cause disease but does trigger an immune response.
Moderna’s vaccine candidate, which was developed in collaboration with scientists at the National Institutes of Allergy and Infectious Disease, is made out of messenger RNA; hence the phrase mRNA in the vaccine’s name. This molecule is responsible for carrying the genetic recipes for making different proteins to a cell’s protein production factories. The version inside Moderna’s vaccine carries the instructions for making a little bit of the spike protein that SARS-CoV-2 uses to infect human tissues. The idea is that a vaccine recipient’s cells will produce this partial spike protein, which will train their bodies’ immune systems to recognise the virus and attack it the next time it shows up.
Still a new strategy, this kind of vaccine has never been approved for use or manufactured at scale. But Moderna’s safety trial, which began in March—the first SARS-CoV-2 vaccine to be injected into human volunteers—appears to have gone well enough that the FDA has greenlighted the next phase. It hopes to gain approval as soon as 2021, though Moderna’s not waiting for those results to start ramping up manufacturing. Last week, the company announced a 10-year partnership with Swiss drugmaker Lonza, which it expects to boost its production to tens of millions of doses per month in 2020 and hundreds of millions per month in 2021.
On the same day Moderna administered its first-out-of-the-gate vaccine, a company in China called CanSino Biologics got the green light to begin Phase I tests of two of its vaccine candidates. Like Oxford’s, they consist of a harmless viral vector that’s been genetically tweaked to look just enough like SARS-CoV-2 to trigger an immune response. In April, one of these vaccines entered Phase II, and researchers in Hubei province are now trying to recruit 500 people for the study. Other vaccine efforts are also showing early promise. Last week Monday, 15 healthy volunteers in New York received the first doses of an mRNA-based vaccine similar to Moderna’s, called BNT162.
Produced by Pfizer and a German pharma company called BioNTech, BNT162 is one of four genetic vaccine candidates the two companies are jointly developing to fight SARS-CoV-2. Over the next few weeks, the Phase I trial will enroll 360 people in four different research hospitals to see how safe these different variations are compared to a placebo. Researchers will monitor patients for the next two years, looking for signs of side effects as well as any antibodies their bodies produce against SARS-CoV-2. But since most bad reactions happen right away, the scientists should know in three to four months if the vaccine candidates are safe and have an idea of which one of the four works best.
At the University of Pennsylvania, researchers are also testing the safety of another genetic vaccine, produced by the nearby biotech company Inovio. Codenamed INO-4800, the vaccine is made out of synthetic DNA instead of RNA, though the principle is the same. Packaged into the DNA is a section of the SARS-CoV-2 spike protein. Inovio is testing two doses of INO-4800 in 40 healthy volunteers split between UPenn and the Center for Pharmaceutical Research in Kansas City, Missouri. In addition to these vaccine candidates, there are also two others currently in human trials in China. Both are chemically inactivated versions of the virus, one developed by Sinovac and one developed at the Beijing Institute of Biological Products. According to a list assembled by the WHO, there are a further 71 vaccine candidates that could soon follow.
Explaining the three stages of clinical trials
Most scientists believe that having a vaccine, which would teach people’s immune systems to recognize and fend off the virus before an infection can take hold, is what the world really needs right now. With widespread fears that the consequences of a prolonged global economic lockdown can be catastrophic, experts are of the view that everybody wins if an inoculated public could get back to work and resume normal life. However, developing a safe and effective vaccine against a new pathogen typically takes years, if not decades.
Generally, clinical testing comes in three stages. The first phase involves a few dozen healthy volunteers, Phase II expands to several hundred in an outbreak area, and Phase III repeats the experiment with several thousand. Then drug administration officials must review the data and decide if the shot is safe and effective enough to approve. But in the face of the current global pandemic, scientists, pharmaceutical companies, and regulators are sprinting at record-shattering speeds to test hundreds of vaccine candidates. Without clinical trial data, it’s impossible to predict which contenders will emerge from the onslaught of experiments as the most successful.
After scaling preclinical trials, the first test in testing an experimental drug or other treatment in human beings involves evaluating the drug’s safety and toxicity at different dose levels. Phase two testing is done with several hundred volunteers with the aim to see how the volunteers’ immune systems respond to the vaccine and whether it makes them immune to the disease. At this stage, safety and side effects are also studied before any vaccine candidate receives the nod to proceed to phase three testing. Phase three trials involve giving a vaccine to large numbers of people to see whether it works, whether it is safe and whether it has unknown or rare side effects. These can range from thousands to tens of thousands of volunteers.
In other words, when candidate vaccines make it to human clinical trials, they first go through Phase 1 trials primarily to test the vaccine’s safety, determine dosages and identify any potential side effects in a small number of people. Phase 2 trials further explore safety and start to investigate efficacy on larger groups. The final stage, Phase 3 trials, which few vaccines ever make it to, are much larger, involving thousands or tens of thousands of people, to confirm and assess the effectiveness of the vaccine and test whether there are any rare side effects that only show up in large groups.
World leaders pledge $8 billion for vaccine
Recently, in a video meeting hosted by the European Union, world leaders, nonprofits and celebrities responded to calls to fight the pandemic last week. They pledged $8 billion to fund laboratories working to develop and produce a vaccine. The money was for the Access to COVID-19 Tools Accelerator or the ACT Accelerator, a collaboration between the WHO and governments, nonprofits, and industry worldwide. It was launched on April 24. They all pledged to work with and support the effort. However, the US was conspicuously missing in the cavalcade of donors, despite being a major contributor to global health initiatives.
“We know that as long as anyone is at risk from this virus, the entire world is at risk – every single person on the planet needs to be protected from this disease,” the collaboration’s mission statement said in part. The three-hour fundraising effort was like an old-fashioned telethon, with a leader from each country taking a few minutes on the video call to pledge money.
Still a long journey ahead
By some estimates, it is likely the world gets a vaccine in the coming months. Some say it could take longer than 18 months. Or scientists may not be able to manufacture a vaccine at all. But if scientists succeed, there will likely be enormous advantages for whoever controls it as the competition to be the first will likely engender a new wave of geopolitics the first country to the finish line will be first to restore its economy.
To this end, United States President Donald Trump is putting everything he’s got into a research effort dubbed Operation Warp Speed, which pulls together pharmaceutical companies, government agencies, and the military. So is China, which appears to have a head start at a time the two countries are already engaged in a fight for dominance in every aspect of global affairs. That is why development professionals are saying the stakes could not be higher for finding a vaccine against a virus that has claimed more than a quarter of a million lives and shattered global economies.
Although many world leaders are talking about global collaboration, it is obvious that national interests will dominate, as the government that can immunise its workforce first stands to gain in terms of economic advantage, validation of its technological prowess, and international influence. Both the US and China have played down talk of competition, no vaccine has ever been made on the kinds of schedules being targeted, which counted in months rather than years. President Trump said recently that the US is working with both Britain and Australia on vaccine projects, and wasn’t focused on geopolitics or who got there first. “I really don’t care. If it’s another country, I’ll take my hat off to them. We have to come up with a vaccine,” he said. American authorities said the US expects to be able to start manufacturing the drugs itself, whoever makes the scientific breakthrough.
However, still in the throes of the pandemic, signs of geopolitical rivalry have been obvious as the trust seems to be lacking among allies. The US has signaled that its own efforts are focused on protecting the American people first, which is primarily “to develop a vaccine for the people of the United States.”
But many believe China’s research process is, for now, more advanced, with a total of 508 volunteers joining a second phase trial for a potential vaccine that the Chinese Academy of Military Medical Sciences is developing with a Tianjin-based company, CanSino Biologics. Results from the trial could be known as soon as this month. Also, Russia has at least four vaccine projects underway, including at Novosibirsk Vector. The goal is for Russia to make sure its own population has protection without being dependent on its rivals. Others are in the mix, too, with the UK saying that if a promising Oxford University project is successful, Britons will be at the front to the line. France and Germany are also leading the charge for a more cooperative approach, securing pledges of 7.4 billion euro ($8 billion) at a virtual Group of Twenty fundraiser on May 4; while the Bill & Melinda Gates Foundation has said it will build manufacturing capacity to make as many seven vaccines available even before they exist, an unprecedented effort to ensure wide and rapid availability. (The Nation)