The coronavirus vaccine frontrunners are advancing quickly. Here's where they stand.
Scientists, drugmakers and governments are moving with unprecedented haste to develop a vaccine against the new coronavirus.
The fastest of them have already delivered promising data from initial human studies, and further results from larger tests should come quickly over the next three to six months.
The goal, at least in the U.S., is to have a vaccine ready for use in some fashion by the end of the year, or early next. Doing so would be a scientific feat with few parallels. No vaccine has ever been developed so quickly, never mind manufactured for the world.
Vaccine frontrunners have progressed quickly
- 1st volunteer given vaccine▼
- 1st volunteer given vaccine
- 1st data available
- Start of late-stage study
- 1st supply available
Researchers' success or failure could determine whether the virus becomes endemic, recurring in countries around the world year after year, or is ultimately checked.
With the health of their citizens at stake, governments are investing enormous sums of money into vaccine research and development, and to prepare to manufacture and distribute what will likely need to be billions of doses necessary to keep infection at bay.
Vaccines have become political as well. Russia, seeking a Sputnik-like achievement to tout to the world, approved a vaccine before completing testing, while China has cleared experimental shots for limited use in the military and, reportedly, high-risk groups.
In the U.S., the Trump administration has unveiled "Operation Warp Speed," so far pledging more than $11 billion in funding and support for seven candidates. Concerns have grown, however, that President Donald Trump, looking to boost his reelection prospects, will pressure the Food and Drug Administration to grant an early emergency authorization.
Lucrative supply deals between drugmakers and governments should secure early vaccine access for the U.S, Europe and other developed nations like Japan and Canada. The rest of the world might not be so fortunate, even with well-intentioned efforts by the World Health Organization and groups like GAVI, The Vaccine Alliance.
"It's not like we can expect 7 billion doses the day after licensure so we can vaccinate the whole world," said Emory University vaccines expert Walter Orenstein. Yet, to truly curb circulation of the SARS-CoV-2 virus in humans, getting vaccines to nations wealthy and poor will be a vital mission.
Expect a flurry of data, new answers and likely fresh questions to come through the remainder of 2020. Here's where things stand for 13 of the most advanced, most promising or best funded vaccine candidates in the pipeline.
One of the great allures of messenger RNA technology — an unproven approach that instructs cells to produce specific proteins — is that it can be used to make a vaccine much faster than traditional methods. Moderna's experimental coronavirus vaccine is proof.
The vaccine went from a computer design in January to human study in just three months, making Moderna the first U.S. company to reach that point.
Since then, Moderna has kept up its record pace. Snippets of Phase 1 results came in late May, as did the start of a mid-stage trial. A Phase 3 study began on July 27, and was almost fully enrolled by mid-October, making the company's effort one the best hopes for a vaccine by early next year.
Results to date showed Moderna's shot can spur immune responses in both young and elderly adults that were similar or higher to what's been observed in recovered COVID-19 patients. The vaccine also appears safe, although only the large trial now underway can fully answer that question.
Much still needs to go right. No mRNA vaccine has been proven to prevent an infectious disease, and none have been manufactured and distributed at scale, let alone during a pandemic. Moderna's findings to date are encouraging, but don't guarantee success.
The company has also come under scrutiny, both for the price it plans to charge the U.S. government as well as for the intellectual property it claims for its vaccine. Government scientists have supported Moderna's work and could hold rights to some of the underpinning technology. Seemingly in response, Moderna has said it will not enforce patent rights related to its vaccine technology for the duration of the pandemic.
Much as Moderna was the early frontrunner in the U.S., China's CanSino Biologics appeared to progress the quickest among the many Chinese groups researching coronavirus vaccines.
Around the same time the first trial volunteer received Moderna's shot in Seattle, researchers 6,000 miles away in Wuhan, China were enrolling healthy adults into a Phase 1 study of CanSino's prototype.
In May, results from that trial were published in a peer-reviewed medical journal, allowing CanSino and its Chinese government partners to claim the scientific distinction of being first to do so in the global vaccine race.
Data suggested inoculation spurred immune responses in treated participants, an encouraging first step. The data didn't prove whether the vaccine's effects would actually be protective against infection, however, and side effects forced researchers to scrap the highest dose.
CanSino's fast progress appears to have slowed, as the company has struggled to launch a Phase 3 trial to prove its shot. Fewer COVID-19 cases in China pushed Chinese vaccine developers to seek study sites overseas, but an agreement between CanSino and Canada reportedly came undone. Late-stage studies are now recruiting volunteers in Pakistan and Russia, according to a U.S. clinical trials database.
CanSino's choice of vaccine design may limit the shot's potential, though. Pre-existing immunity to the adenovirus, or viral vector, that CanSino uses to deliver its vaccine appears to compromise its effectiveness.
Inovio looks to have fallen behind in the race, having no big pharma partner and assembling only about $100 million in external funding.
A partial clinical hold imposed by the FDA in late September, meanwhile, will keep the company from starting a planned late-stage study until at least November. Inovio had initially hoped to begin the study during the summer, and then delayed the launch until September.
Inovio's candidate uses DNA to coax cells to produce coronavirus proteins, thereby stimulating an immune response to protect against infection by the virus. To allow the DNA molecules to enter cells, Inovio uses a process called electroporation, a small electrical pulse that opens small pores in cells. The device was the subject of some of the questions posed to Inovio by the FDA.
Little data is available on how the vaccine has performed so far. Summary results from a small Phase 1 trial were disclosed by the company in June.
While Inovio's manufacturing capacity is much less than big names like Pfizer and Moderna, the biotech recently boosted its potential supply lines. The company signed Thermo Fisher to its manufacturing consortium, with the hope of producing 100 million doses in 2021.
Its initial round of manufacturing deals, with Ology Bioservices and Richter-Helm BioLogics, would have produced only 1 million.
Inovio's production plans, however, are threatened by ongoing litigation involving two companies, VGXI and GeneOne Life Science, that had been contracted to supply materials for its vaccine.
Inovio had sued the two companies, claiming they refused to transfer technology to Ology and Richter-Helm. VGXI countersued, charging breach of contract and other claims. The lawsuit is ongoing in a Pennsylvania court.
In the U.S. and Europe, vaccine developers have bet on newer technologies, such as messenger RNA or viral vectors, that, while less established, offer advantages in speed.
Several Chinese companies, however, have moved equally quickly using tried-and-true approaches such as inactivated virus vaccines. Used for hepatitis A, influenza and rabies, these vaccines consist of viruses rendered uninfectious either through heat or harsh chemicals.
Six of the 30 or so coronavirus vaccines now in clinical testing use a disabled form of SARS-COV-2. Five of them were developed by Chinese groups, including Beijing-based Sinovac Biotech.
Sinovac wasn't the first to get going. The company began human testing of its candidate in April. But it's since progressed through Phase 2 and, in late summer, began Phase 3 studies of its vaccine in Brazil and Indonesia, where coronavirus cases are still climbing.
The shot was reportedly approved for emergency use in China in late August.
Details on Sinovac's tests to date have slowly trickled out. A manuscript made available in early August showed vaccination was well tolerated and produced antibodies against SARS-CoV-2, but at levels lower than what's been reported for other candidates.
Sinovac is listed on the Nasdaq stock exchange, but trading in its stock has been halted since February 2019 — the result of a dispute with an activist investor over control of the company.
Moderna isn't the only high-profile biotech aggressively pushing forward with a promising, but unproven technology.
Across the Atlantic, in Mainz, Germany, BioNTech is developing multiple mRNA vaccines for the coronavirus. The drugmaker had already been working with Pfizer on an influenza vaccine for over a year when COVID-19 emerged as a global threat.
The two companies shifted gears toward coronavirus research in mid-March, starting work even before their legal teams had produced a contract.
Pfizer and BioNTech quickly started clinical trials in Germany and the U.S. But unlike Moderna and other early starters, the pair advanced four prototypes, each with subtle differences, before choosing one to take into late-stage testing. A Phase 2/3 trial began on July 28 and has now surpassed its initial goal of enrolling 30,000 volunteers, although the companies are recruiting another 14,000 to ensure better representation of minority groups.
Phase 1 results on two of those prototypes have been disclosed, showing vaccination spurred encouraging immune responses in healthy adults given the shot. The vaccine version Pfizer and BioNTech chose for late-stage testing appeared to be safer in older individuals than the first one they tested.
Albert Bourla, Pfizer's CEO, repeatedly suggested late-stage data could come by the end of October. But by Oct. 27, too few cases of COVID-19 had occured in the study to trigger a meeting of the committee reviewing the trial's data, making that promise unlikely to be kept. Pfizer has said it won't ask the FDA for an emergency approval until sometime in November at the earliest.
Pfizer and BioNTech have contracted with the U.S. to supply 100 million doses. But Pfizer isn't relying on government funding for its testing and manufacturing, claiming it's been able to move faster on its own. BioNTech, however, in mid-September received nearly $450 million from the German government to support vaccine development — money the biotech will use to cover its share of expenses in the partnership.
Bourla has said he expects Pfizer to spend more than $1 billion on a vaccine.
When Chinese scientists made the new coronavirus' genetic sequence available in January, researchers at the University of Oxford were more prepared than most.
A team there was already working on a vaccine for the virus that causes MERS, a close cousin of SARS-CoV-2. The Oxford researchers quickly adapted their work and, by April, had started a large Phase 1 trial of their new vaccine in the U.K.
AstraZeneca signed on to help soon after, licensing the vaccine and beginning efforts to prepare for manufacturing hundreds of millions of doses.
Their speed — larger studies began in May, June and earlier this month — made AstraZeneca and Oxford's vaccine among the world's leading efforts and the subject of political tug-of-wars over who would get access.
But, in a notable setback, an unexplained neurological illness in one participant in the U.K. study forced AstraZeneca and Oxford to halt testing worldwide in early September.
Such safety reviews are common in clinical trials, and are a sign of appropriate caution in assessing whether a vaccine may have caused an adverse reaction. Little information was made available on the participant's illness and whether it shared anything in common with neurological symptoms previously observed in another trial volunteer that were ruled unrelated to vaccination. Trials were briefly paused following that case as well.
Surprisingly, just six days after the global vaccination halt, the U.K. drugs regulator agreed with an independent study committee that clinical trial sites in the U.K. could safely resume testing.
A review by the FDA took much longer, however, dragging on for more than six weeks before the regulator gave AstraZeneca a green light on Oct. 23 to resume vaccinations. The agency's investigation was not able to link the illnesses to AstraZeneca's shot, according to The Wall Street Journal.
Novavax has spent more than three decades trying to break into a vaccine business dominated by large pharmaceutical companies. Now that it's finally on the brink, with a preventive flu treatment nearing regulatory review, it's become involved in coronavirus vaccine development, too.
Novavax was among the first companies to begin working on a COVID-19 vaccine. By the end of May, it had won a large grant from the nonprofit Coalition for Economic Preparedness Innovations and started an initial clinical trial of its shot. Its shares climbed nearly 9-fold in the process.
The biotech was further boosted in July by support from the U.S. government, which committed $1.6 billion to fund late-stage testing of Novavax's vaccine and to buy 100 million doses.
In September, Novavax published full results from its Phase 1 study, which showed its vaccine spurred encouraging immune responses. Like other experimental shots, vaccination was associated with mostly mild side effects in most trial participants. A late-stage study began in the U.K. in late September, aiming to enroll 10,000 people.
Still, Novavax faces an uphill climb to prove its technology. Its vaccine platform, which uses recombinant proteins to trigger an immune response, has a mixed track record. Before Novavax reported in March its flu vaccine succeeded, two late-stage studies of a potential shot for respiratory syncytial virus failed. Other experimental vaccines for coronavirus cousins SARS and MERS never made it to late-stage testing.
Deals with Emergent BioSolutions and the Serum Institute of India, as well as an acquisition of Praha Vaccines, have given the company the manufacturing muscle to produce over 2 billion doses of its vaccine annually beginning in 2021. The company has so far promised 76 million of those doses to Canada and another 60 million to the U.K.
Russia approved Gamaleya's vaccine on August 11, less than two months after the first studies in humans began and, critically, before large-scale trials prove whether it protects against COVID-19.
The approval, which was announced by President Vladimir Putin, is the most significant example yet of how the race to develop a coronavirus vaccine has been cast in geopolitical terms.
Like the U.S., China and Europe, Russia has pushed for faster development, spurring concerns that safety risks might go overlooked or crucial steps bypassed.
In the case of Gamaleya's vaccine, the government's urgency led to an approval following two small trials in just 76 volunteers. Such studies are designed to get an early sense of a vaccine's safety, as well as whether the shot spurs an immune response.
That data was finally published on Sept. 4 in The Lancet, showing Gamaleya's vaccine stimulated an immune response equal to that of patients who have recovered from coronavirus infections. However, shortly thereafter, several dozen scientists penned a "letter of concern" regarding possible inconsistencies in the data shared by Gamaleya researchers.
Proving protection from either coronavirus infection or disease requires larger, placebo-controlled tests involving thousands of participants. Those are coming for the Gamaleya vaccine, Russia's health minister said in early August, but the shot will be "gradually introduced" for groups like healthcare workers and teachers before then.A U.S. database of clinical trials shows a late-stage study of the shot has yet to begin recruiting patients.
A mass vaccination campaign is reportedly planned for the fall, raising the risk that the shot is given widely before its side effects are fully known.
In early March, the American CEO of CureVac, Daniel Menichella, joined the heads of other coronavirus vaccine developers in a meeting with President Donald Trump at the White House.
A little more than a week later, Menichella was out as CureVac's CEO and the German biotech was at the center of swirling rumors that the U.S. had sought to buy the company, or its research.
Seemingly in response, the German government has since invested 300 million euros in CureVac, securing a 23% stake. CureVac added another $500 million through private investments, an alliance with GlaxoSmithKline and an initial public offering in the U.S. Much of the proceeds will help develop its coronavirus shot.
CureVac's vaccine, which has also been funded by CEPI, uses messenger RNA to encode the coronavirus' spike protein. A Phase 1 study of the candidate began in June, enrolling healthy adults in Germany and in Belgium, and results are due soon.
In late September, a mid-stage study was launched in Peru and Panama. If results are positive, CureVac plans to further study its candidate in a Phase 2b/3 trial that would enroll as many as 30,000 participants. The company says it can manufacture hundreds of millions of doses.
Some 405 million of them could go to the European Union under a proposed supply deal, and a 75 million euro loan from the European Commission could help expand production further.
Clover's candidate was the second protein-based vaccine to begin human testing for the new coronavirus, trailing only Maryland-based Novavax when its Phase 1 study began in mid-June.
Like the name suggests, protein-based vaccines are designed to expose the body's immune system to viral proteins. In the case of SARS-CoV-2, that's the spike protein which the virus uses to enter cells.
Protein-based vaccines are often paired with adjuvants, compounds that help boost the immune response to vaccination. Clover's trial is testing its candidate together with adjuvants developed by GlaxoSmithKline and Dynavax, potentially providing a proving ground for those companies' technologies in inoculating against SARS-CoV-2.
No specific results are available yet, but Clover said in September that early results from 150 volunteers showed the vaccine to be safe and capable of generating antibody responses. A Phase 2/3 study is planned to start before the end of the year.
CEPI has provided Clover with additional financial muscle, pledging nearly $70 million in July to fund the Phase 1 study and prepare manufacturing capacity should the candidate succeed.
J&J was first among larger drugmakers to pursue a coronavirus vaccine, announcing in late January plans to develop one using the same technology that underpins several other of the pharma's experimental vaccines.
Initially, J&J didn't expect to begin clinical study until September, a timeline that would have previously marked record speed but in the COVID-19 age appeared more deliberate.
The pharma sped up its plans, however. An initial study began in late July in the U.S. and Belgium. A 60,000-volunteer, global Phase 3 study — the largest of any coronavirus vaccine study so far — began on Sept. 23. The company is aiming to prove a one-shot regimen, a goal others have found too challenging to achieve.
Early data made public in September suggested that goal might be possible, showing a single injection led to immune responses in nearly all tested participants. Safety results were harder to parse, since the study researchers still remain blinded to whether individuals in the trial received the vaccine or placebo. Side effects were more common and more severe in younger participants, however.
On Oct. 12, J&J paused vaccinations in all ongoing studies, after a participant got sick with an unexplained illness. Such safety reviews are planned for and happen relatively routinely in large clinical program's like J&J's, but the halt was a notable speed bump for one of the most well regarded vaccine efforts. Less than two weeks later, an independent panel monitoring board recommended vaccinations resume, finding no evidence to connect J&J;'s vaccine with the volunteer's illness.
J&J expects to be able to supply 1 billion doses of its vaccine, beginning early next year. The drugmaker's scale has made it a natural partner for governments looking ahead to widespread inoculation drives. The U.S. government has pledged nearly $1.5 billion to J&J's work and for future supply of its shot.
When two of the biggest vaccine manufacturers team up, the world should pay attention to what they're doing. In April, Sanofi and GlaxoSmithKline agreed to join forces, the former contributing its protein-based vaccine technology and the latter its immune-boosting adjuvants, both of which have previously been used against influenza.
They probably won't be the first to market, however. Their development timeline is months behind that of Moderna, Pfizer and even Novavax, which is using a similar approach.
The first human study of Sanofi and GSK's vaccine began in September. Initial results are expected in December, around which time a late-stage study should follow. That puts the two companies on track for potential approval in the first half of 2021, if all goes well. Multiple shots could be available by then.
What Sanofi and GSK might be able to bring, though, is a more potent vaccine. Adjuvants are added to vaccines to enhance the immune response, in theory resulting in stronger inoculation against an invading virus. With herd immunity the goal of any mass vaccination program, public health leaders will want a vaccine capable of preventing infections in at least 70% to 80% of the people who get it.
Sanofi and GSK also boast more support from the U.S. government than any other developer besides Moderna. At the end of July, the U.S. promised $2.1 billion to fund development and clinical testing, as well as manufacturing. Should the shot prove successful, the U.S. would get 100 million doses.
Merck came late to the coronavirus vaccine race, having publicly announced its efforts near the end of May. But, given its track record developing drugs and vaccines for infectious diseases, its involvement shouldn't be underestimated.
Merck also has no interest in being first. The company eschewed newer, less proven technologies that offered advantages in speed. Instead, Merck homed in on approaches it knows it can manufacture at a global scale, and believes will produce immunity quickly, with one shot.
Those preferences led Merck to license two vaccines that use viruses to deliver their payloads. Merck got one by buying privately held Themis, and the other by teaming up with the nonprofit group IAVI. A Phase 1/2 study of the Themis vaccine began in Belgium in early September, while the human testing for the other program will start sometime later this year.
Both harness technologies with which Merck is already familiar. The drugmaker was working with Themis on a measles-based vaccine for chikungunya, and saw enough to believe the approach could lead to an effective single-dose vaccine, said Daria Hazuda, its head of infectious disease discovery. The IAVI program is based on the same approach behind Ervebo, the company's approved Ebola vaccine.
The company, for its part, believes that will make up ground on its rivals later on, given newer technologies like mRNA and DNA vaccines have never been produced at scale, and will almost certainly require booster shots to confer immunity.