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 showing vaccines can protect against COVID-19, and further results from tests of other experimental shots are expected soon.
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
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- Start of late-stage study
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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 in high-risk groups. In the U.S., the Trump administration has pledged more than $11 billion in funding and support for seven candidates through "Operation Warp Speed."
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 advantages to messenger RNA technology — a new drug-making approach that uses genetic instructions to teach cells to make specific proteins — is that it can be used to develop 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, a little under four months later, delivered strongly positive results that indicated the vaccine was 94.5% effective in preventing COVID-19. Data shared by Moderna also show the vaccine appears to protect people from the severe disease that leads to the worst health outcomes.
The finding, which was based on a preliminary look at the first 95 cases of COVID-19 in the study, is a powerful — and hopeful — signal that raises optimism around other vaccines in development might work too. Taken together with a similarly positive readout from Pfizer and BioNTech, which in early November said their shot was more than 90% effective in preventing COVID-19, researchers can now more confidently say their approach to vaccination will prove protective.
Crucially, the vaccine also appeared safe, although a fuller accounting of the side effects experienced by participants is expected in the coming weeks.
No mRNA vaccine has ever been approved to prevent an infectious disease, however, and none have been manufactured and distributed at scale, let alone during a pandemic.
Should Moderna's vaccine receive an emergency clearance, supplies would be limited initially to several tens of millions of doses before the company and its manufacturing partners can sufficiently ramp up production next year.
Success notwithstanding, Moderna 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. 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, kept the company from conducting further study until mid-November, when the agency cleared a Phase 2 trial to begin. 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 FDA's concerns, which the company plans to more fully address via the Phase 2 trial now launching.
Should those questions be resolved, Inovio would then launch a Phase 3 trial that remains on partial clinical hold, the company said Nov. 16.
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 wasn't the only high-profile biotech to aggressively push forward with the promising, but until now unproven, messenger RNA technology.
Across the Atlantic, in Mainz, Germany, BioNTech started work on an mRNA vaccine for the coronavirus early on in the pandemic and agreed to partner with Pfizer in mid-March, joining forces with the larger drugmaker even before their legal teams had produced a contract.
Unlike Moderna and other frontrunners, 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 enrolled some 44,000 volunteers over the course of three months.
Phase 1 results on two of those prototypes showed 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, briefly putting the company in the middle of a political controversy in the U.S., where President Donald Trump had publicly hoped for a pre-election vaccine boost. Instead, the first look at Pfizer's Phase 3 results came six days after the election, when the company and BioNTech said an interim analysis had found their shot more than 90% effective at preventing COVID-19 — a better-than-expected outcome and major scientific achievement.
Further details released by the companies showed the vaccine to be 95% effective at the trial's final analysis, which was based on 170 cases of COVID-19 that occured in the study. Only eight of those cases were among vaccinated volunteers.
Pfizer and BioNTech followed those results up quickly with an application to the Food and Drug Administration for an emergency approval. An FDA advisory committee is set to review the vaccine on Dec. 10.
The companies have contracted with the U.S. to supply 100 million doses. Pfizer hasn't been relying on government funding for its testing and manufacturing, however, claiming it's been able to move faster on its own. In mid-September, BioNTech did receive 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 will 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 September — 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. While regulators in the U.K. and other countries quickly signed off on a trial restart, a review by the FDA took much longer, dragging on for more than six weeks before the agency gave AstraZeneca a green light on Oct. 23 to resume vaccinations.
While AstraZeneca's large U.S. trial is still recruiting volunteers, studies in the U.K. and Brazil delivered preliminary data in late November showing the vaccine could protect against COVID-19. The results were somewhat confusing, however, showing dramatically different protection rates between a larger group that received two full doses of the shot and a smaller group that was given — apparently on accident — a half dose and then a full dose. On average, AstraZeneca said, the vaccine was 70% effective.
While that number is below what Pfizer and Moderna have reported for their candidates, AstraZeneca and Oxford's vaccine can be more easily distributed, potentially aiding global immunization campaigns.
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, the drugmaker'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, and will enroll 15,000 people. Another is set to begin in the U.S. by the end of November, slightly after when the company initially expected.
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 Aug. 11, less than two months after the first studies in humans began and, critically, before large-scale trials proved whether it could protect 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. Gamaleya, with help from Russia's government and sovereign wealth fund, got started on a late-stage trial of its vaccine in late August, as the government was already beginning to distribute the shot.
On Nov. 11, two days after Pfizer and BioNTech rallied the world's spirits with an announcement their vaccine was more than 90% effective in preventing COVID-19, Gamaleya was out with a similar, albeit shakier, claim.
Researchers running Pfizer and BioNTech's Phase 3 study, which has enrolled some 44,000 people, had based their estimate on an analysis of 94 cases of COVID-19. Gamaleya investigators, by comparison, concluded their shot was 92% effective based on just 20 cases among the 16,000 who have so far received the vaccine or placebo, giving their claim less statistical weight. Updated results after 19 more case brought the rate down a tick, to 91%, Gamaleya said in late November.
Gamaleya's vaccine, though, has already been given to another 10,000 volunteers, mostly healthcare workers and high-risk individuals, outside of the trial. The institute said data from those individuals confirmed an efficacy rate of greater than 90%, but didn't offer any further details.
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. The company shared a summary of results from that study in early November, indicating a high dose of its vaccine led to a immune response similar to those observed in recovered COVID-19 patients.
A mid-stage study was launched in Peru and Panama in mid-September and CureVac plans to launch a Phase 2b/3 trial that would enroll as many as 30,000 participants before the end of the year. 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.
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.