This post has been updated.
There are currently more than 150 different COVID-19 vaccines under development. Of these, more than 50 have reached human trials and, as of the end of March, three vaccines have been granted Emergency Use Authorization (EUA) from the FDA. These include two mRNA-based vaccines—one from the biotechnology company Moderna and the other from drug giant Pfizer—and one so-called viral vector vaccine from Johnson & Johnson.
As of March 2021, other promising vaccine candidates include AstraZeneca’s vaccine as well as one from a Maryland-based biotechnology company called Novavax. While AstraZeneca reported results of a phase 3 trial back in November, the company has run into a number of issues since then. During AstraZeneca’s clinical trials, some participants were mistakenly given a half-dose of the vaccine for their first shot, which surprisingly provided a higher efficacy than the intended dosage. Further research was needed to understand these findings, which has delayed the vaccine getting an emergency use authorization from the FDA. On March 22, 2021, the company reported additional Phase 3 results, but those results also had issues: AstraZeneca failed to use the most up-to-date data and once it did include the newer data, the percent effectiveness in the Phase 3 trials shifted from 79 percent to 76. The FDA will take all this into account when making a decision. Meanwhile, Novavax released results of its phase 3 clinical trial on March 11, and they were promising. They showed 96 percent effectiveness against the original strain, but less effectiveness against newer variants. The vaccine candidate was 100 percent effective against severe disease. It’s likely the company will apply for emergency use authorization in the US soon.
Many of the other candidates, however, will fail somewhere along the vaccine development pipeline, which includes three rounds of clinical trials with increasingly large pools of volunteers to assess their safety, efficacy, and ability to prompt a response from the immune system. And for those that achieve authorization, there remain important questions that we’ll need more time and further research to answer, including how long the immunity they offer from COVID-19 lasts. Another key question is whether vaccines that protect people from getting sick will also prevent them from carrying and unwittingly transmitting the virus (for now, it’s important for people who have been vaccinated to continue wearing masks and practicing social distancing). Additionally, scaling up production and distributing vaccines to the general public will take months in the US and longer still in many other parts of the world.
Still, this is an extraordinary achievement. Never before has any vaccine been designed, tested, and released within a year. The COVID-19 pandemic has brought unusual circumstances, though, that have allowed vaccine makers to move more quickly than usual. Among these are generous funding, a streamlined bureaucratic process, and a disease that continues to spread like wildfire in many areas where vaccine trials are taking place, which means the vaccine candidate’s ability to protect people from the virus is more rapidly apparent.
“What we’ve seen is a real collaborative and collegial approach to helping person-kind and that has come from the funding agencies … and then the willingness of scientists across the world to work together to develop this and to share the information, so this is a real success story of science,” says Reynold Panettieri, the director of the Rutgers Institute for Translational Medicine and Science. “This pandemic has led to discoveries [that] could not have occurred in one laboratory or with one funding agency.”
Here are some of the strongest vaccine candidates that have either been authorized for limited use or have entered clinical trials.
A crowded field
The COVID-19 vaccine candidates are a diverse lot that have been created from a mix of traditional and experimental strategies.
Some, including those by Pfizer and Moderna, are so-called nucleic acid vaccines that carry fragments of genetic information from the virus. In the case of Moderna and Pfizer, this material is messenger RNA (mRNA), which carries instructions that cells use to build proteins. When human cells “read” the mRNA, which codes for the spike-shaped proteins on the surface of the virus that help it invade cells, they begin pumping out spike proteins. The spike proteins can’t cause illness on their own, but they do prime the immune system to recognize and attack the novel coronavirus, SARS-CoV-2, if the vaccinated person is later exposed to it.
This new technology is promising because mRNA vaccines are easier to mass produce than most traditional vaccines. They also seem to rouse several different parts of the immune system, Panettieri says. Another advantage is that, because they contain only a snippet of genetic material rather than a whole virus, they are expected to be especially safe. However, mRNA is very fragile and these vaccines may need to be stored at ultra-cold temperatures to prevent it from degrading, which will make them challenging to distribute.
Several other promising COVID-19 vaccines contain a harmless virus engineered to carry the genetic sequence that codes for the spike protein on SAR-CoV-2. The vaccine developed by AstraZeneca is one example of this group, which are known as viral vector vaccines. As with mRNA vaccines, this genetic information is used by our own cells to build the spike protein and train the immune system to recognize the novel coronavirus. Two recently-approved Ebola vaccines use this strategy. Researchers have expressed some concerns that the delivery viruses—such as adenoviruses, which cause common colds in humans and other animals—may be similar to ones the body has run across before.
“Our bodies could fight the shuttle virus and it can’t then deliver its cargo,” Panettieri says. “That’s why it may be a little less effective than the mRNA vaccines.”
Other candidate vaccines, including ones from Novavax and Sanofi, are built from protein fragments of disease-causing virus. One common immunization that already uses this technique is the hepatitis B vaccine. Other COVID-19 vaccines include versions of the novel coronavirus that have been “killed” or weakened so they won’t cause disease. There are many existing vaccines that use this strategy, including those for measles, yellow fever, and seasonal influenza.
Pfizer and BioNTech
Status: Phase 2/3, authorized for emergency use in several countries, including the US, and approved in a few countries
The COVID-19 vaccine developed by New York-based Pfizer and the German biotech company BioNTech is the first mRNA vaccine to become available to the public. The vaccine has received emergency authorization in a number of countries, including in the United Kingdom on December 2 and on December 11 in Mexico and the United States. It has been fully approved in Canada and several other countries.
The United States began its vaccination campaign on December 14, 2020, prioritizing healthcare workers and residents of long-term care facilities. Since then the vaccines have become available to much wider swaths of the population, with a majority of states planning to open. It has not yet been approved for use in children under 16 or pregnant people, although the latter group can choose to get vaccinated and many doctors have recommended they do so. (The risk of getting infected with COVID-19 while pregnant is worse than any risk associated with the vaccine.)
The vaccine is given in two injections that take place three weeks apart and must be stored at -94 degrees Fahrenheit. Pfizer and BioNTech first reported that the vaccine is more than 90 percent effective on November 9. On November 18 the companies reported that a more detailed analysis showed the vaccine to be 95 percent effective at preventing infection. A report from the U.S. Food and Drug Administration released on December 8 found that the vaccine’s protection began kicking in within 10 days of the first dose. It appears to work similarly well across age, race, and gender.
Potential side effects of this vaccine include fatigue, fever, aches, and chills, particularly after the second dose. Of about 22,000 people in the phase 3 trial who received the vaccine, four developed a form of temporary facial paralysis called Bell’s palsy. However, this rate isn’t significantly higher than in the general population. After the vaccine became available in Britain, several people with a history of severe allergic reactions went into anaphylaxis but have recovered; people with serious allergies can be immunized but should discuss the vaccine with their doctor first.
The US has secured 100 million doses (enough for 50 million people) of Pfizer and BioNTech’s vaccine. As of the first week of January, CDC reports showed that 15.5 million vaccines had been distributed across the country, and 4.5 million people had received the first dose. This data includes both Pfizer and BioNTech and Moderna’s vaccines (see next section).
Status: Phase 3; authorized for emergency use in the US and Canada
Moderna, a biotechnology company based in Massachusetts, partnered with the National Institutes of Health to develop its mRNA vaccine. The vaccine is given in two doses, four weeks apart. It’s a little hardier than Pfizer’s vaccine and can be refrigerated for a month and frozen for six months.
On November 16, Moderna announced that preliminary data from its phase 3 trial showed that its vaccine was 94.5 percent effective. Two weeks later, the company reported that a more complete analysis showed that the vaccine was 94.1 percent effective. Of the 196 volunteers who caught COVID-19 in the 30,000-person trial, only 11 had been given the vaccine candidate.
The fact that Pfizer and Moderna have reported very similar results bodes well for the promise of mRNA vaccines. “Two different companies using similar technology got almost identical results with regard to efficacy, so that is really intriguing,” Panettieri says.
Moderna’s vaccine was also 100 percent effective at preventing severe cases of COVID-19; all 30 cases of severe COVID-19 occurred in the placebo group. What’s more, it prompted an immune response that lasted for at least three months and it appears to be similarly effective for people of different races. Moderna is now running a phase 2/3 trial of the vaccine in adolescents between the ages of 12 and 18.
Moderna applied for emergency use authorization on November 30. The FDA reported on December 15 that its analysis affirmed that the vaccine is safe and 94 percent effective overall. However, the agency found that it was only 86 percent effective in adults over 65. On December 18 it authorized the vaccine for anyone 18 or older.
Several participants in Moderna’s trial did develop Bell’s palsy, three of whom were in the vaccinated group. The FDA concluded that the participants had risk factors for the conditions, and wrote that “currently available information is insufficient to determine a causal relationship with the vaccine.” People who received the vaccine have also reported fevers, fatigue, aches, or chills—a sign that the vaccine is working as intended to provoke a response from the immune system, experts say.
The FDA’s independent Vaccines and Related Biological Products Advisory Committee met on December 17 to review the effectiveness and safety of the new vaccine and ultimately endorsed the product, finding that it met the criteria for emergency use. The next day, on December 18, the FDA granted the vaccine an Emergency Use Authorization (EUA), and immunizations could begin on December 21. The US has purchased 200 million doses of Moderna’s vaccine, and should become widely available by spring.
Johnson & Johnson
Status: Phase 3; emergency use authorization in the US
Johnson & Johnson’s vaccine uses a relatively rare common-cold adenovirus modified so it can’t replicate inside the human body to deliver genetic material from the novel coronavirus. The New Jersey-based corporation has previously used this strategy to develop a vaccine for Ebola and vaccine candidates for HIV and Zika.
At the end of January, Johnson & Johnson released initial results from its late stage trials. The phase 3 trial was originally designed to include 60,000 volunteers, but was slashed to 40,000 in December because COVID-19 is spreading so quickly in the US that enough participants would likely contract the novel virus to test its effectiveness even with less people overall. The company reported that the vaccine was 66 percent effective in preventing COVID-19 28 days after injection, and 85 percent effective at preventing severe disease.
By late February, newly submitted data suggested that the vaccine was 72 percent effective in the US and 64 percent effective in South Africa. Additionally, it was 86 percent effective against severe COVID-19 in the US and 82 percent effective against severe disease in South Africa, where a variant, which has mutations on the spike protein that the vaccine targets, has become dominant. Further, out of the 22,000 people who received the vaccine in the late-stage clinical trials, no one died or was hospitalized with COVID-19. Based on all this data, the FDA granted the vaccine emergency use authorization on February 27th.
While those results are not quite as impressive as the 94 to 95 percent effectiveness of Pfizer’s and Moderna’s mRNA vaccines, it does exceed the threshold the FDA set for approving vaccines, which is 50 percent efficacy. Unlike many of its competitors, the vaccine is given as a single dose. However, Johnson & Johnson started a second phase 3 trial in November to investigate whether a booster dose may make the vaccine more effective.
In early March of 2021, President Biden announced that Johnson & Johnson and competitor Merck brokered a deal for Merck to help make J&J’s vaccine, though it will still take some time to ramp up production.
Status: Phase 3
Novavax, which is based in Maryland, released results on March 11 of one of its phase 3 clinical trials. Based on results of the trial, the vaccine was found to be 96 percent effective against the original strain of the virus, though it was less effective against newer viral strains. It was 86 percent effective against the B.1.1.7 variant (first detected in the UK) and 55 percent effective against the B.1.351 variant in South Africa. However, for all variants, it was 100 percent effective against severe disease, a key measure. The company plans to present its data to the FDA soon.
Its vaccine candidate is made from SARS-CoV-2 spike proteins grown in moth cells and then mixed with nanoparticles and an adjuvant (a compound that helps create a stronger immune response). Several proteins wind up stuck to each nanoparticle, creating bits that are similar in size to the actual virus that are designed to catch the immune system’s attention. The company hasn’t brought any vaccines to market yet, but it reported promising data from a phase 3 trial for its protein-based influenza vaccine earlier this year.
Novavax expects to provide 100 million doses of its COVID-19 vaccine to the US by May if regulators authorize it. Results from early-stage trials had indicated the vaccine is safe and prompted participants to produce more antibodies than were seen in people who’d recovered from COVID-19, so the recent results of the phase 3 trial are not surprising. Researchers also detected “killer” T-cells, which destroy infected cells, in participants’ blood, indicating a strong immune response. The vaccine is given in two doses and is refrigerated. In recent days, some reports have said that older folks who are now eligible to receive the already-authorized Pfizer and Moderna vaccines have dropped out of Novavax’s late-stage, phase 3 trials. As these approved vaccines become even more available it might make it hard for other Novavax (and other drug companies) to finish their necessary trials.
University of Oxford and AstraZeneca
Status: Phase 3; emergency use in the UK and India
For this vector vaccine, researchers selected an adenovirus that typically infects chimpanzees to ferry the SARS-CoV-2 genes into human cells.
At the beginning of the pandemic, scientists at the University of Oxford had already designed a similar vaccine for Middle East respiratory syndrome (which is caused by another member of the coronavirus family) that had entered clinical trials. Their experience gave them a head start on developing and testing a COVID-19 vaccine, further helped by British-Swedish drugmaker AstraZeneca.
Despite the early lead, AstraZeneca has run into a number of issues getting the vaccine from clinical trials to the FDA. During clinical trials, some participants were mistakenly given a half-dose of the vaccine for their first shot (the vaccine is given in two doses separated by four weeks). Perplexingly, the efficacy of the vaccine in this group was 90 percent, while only being 62 percent in the group that received the intended full dose. The vaccine may also have prevented severe cases of COVID-19 in both groups.
The AZD1222 vaccine can be stored for at least six months in a conventional refrigerator, which would make it relatively easy to distribute. The US has ordered at least 300 million doses of the vaccine, but the FDA hasn’t yet authorized its use. The subset of patients that were given the wrong dose of the vaccine is a pretty serious error and unlikely to get past the FDA’s intense vaccine authorization process without further review.
On March 22, 2021, AstraZeneca released the latest results from its ongoing Phase 3 trial, which originally noted that the vaccine was 79 percent effective overall against symptomatic COVID-19. It was later reported that the company was using data that slightly outdated and an independent review board working with the National Institutes of Allergy and Infectious Disease (NIAID) accused the company of cherry-picking its data to make the vaccine more effective. Later that week, the company released a new statement stating that with the most up-to-date data, the vaccine was now 76 percent effective, which is still above the efficacy threshold to authorize a vaccine for use. The vaccine is still 100 percent effective against severe disease. The FDA will need to take all this into account when deciding when or if to grant the vaccine emergency use authorization.
In the UK, the vaccine was approved for use on December 30 and the country began distributing it on January 3. It’s also one of the first two vaccines approved in India. In December, AstraZeneca announced plans to collaborate with Russia’s Gamaleya Research Institute to see whether combining their two COVID-19 vaccines could make them more effective.
A pre-print study (and not yet peer-reviewed) posted on February 3, suggests that the vaccine could be highly effective in preventing the disease from spreading around. During the late-stage trials, participants were swabbed once a week to detect the virus. The researchers reported a 67 percent reduction in positive swabs after the first dose. Scientists still can’t definitively say if COVID-19 vaccines prevent transmission (meaning someone could be vaccinated but still pass it along to others), but this study and others like it will provide a clearer view.
Status: Phase 3, limited use in China
Chinese biopharmaceutical company CanSino Biologics collaborated with the Academy of Military Medical Sciences to produce a vaccine that uses a weakened adenovirus that is unable to replicate inside the human body to deliver SARS-CoV-2 genes.
On June 25, 2020 China granted CanSino’s vaccine approval for military use for one year. Phase 3 trials for the vaccine—which can be refrigerated and is given as a single dose—began in August of last year. As of February, the vaccine has an efficacy of 65.7 percent for preventing symptomatic illness and is more than 90 percent effective at preventing severe illness with just a single dose required.
Status: Phase 3, limited use in China, Hong Kong, Thailand, and Indonesia
Chinese firm Sinovac Biotech received emergency approval to begin immunizing high-risk groups such as healthcare workers this summer. Its COVID-19 vaccine is made from an inactivated, or “killed,” form of SARS-CoV-2 that is refrigerated and delivered in two doses separated by two weeks. SinoVac has previously developed inactivated virus vaccines that have been approved for swine flu; avian flu; hepatitis A and B; and hand, foot, and mouth disease. Results from CoronaVac’s phase 1 and 2 trials, which were published in November, suggest, while the vaccine did prompt an immune response, it caused volunteers to produce fewer antibodies than people who recovered from COVID-19 did. Another trial, conducted by Brazilian researchers found the drug to be just over 50 percent effective. 50 percent is the minimum level of of effectiveness a coronavirus vaccine needs to be approved in the United States and many other countries, but many other vaccines have been far exceeding that. Still, several Asian countries began using it in early January.
Status: Phase 3, approved in China, U.A.E., Bahrain, and Egypt
The state-owned Chinese pharmaceutical company Sinopharm is testing two inactivated virus vaccines for COVID-19. Both received emergency approval over the summer in China for high-risk groups such as healthcare workers. One of the vaccines, which is given in two doses, was developed by the Beijing Institute of Biological Products. It received emergency approval in the United Arab Emirates in late September, followed by full approval on December 9. Bahrain approved the vaccine on December 13, and Egypt followed on January 3. Countries that were early to sign on reported that the vaccine is 86 percent effective, although Sinopharm had not released data from its phase 3 trials to verify this. According to the UAE’s Ministry of Health and Prevention, the vaccine was also 100 percent effective in preventing moderate and severe cases of COVID-19. The Chinese government fully approved the Sinopharm and Beijing Institute of Biological Products vaccine on December 30. Pakistan has also signed a deal to purchase doses.
Sinopharm’s second inactivated virus vaccine for COVID-19 was developed by the Wuhan Institute of Biological Products. Results from phase 1 and 2 trials for both vaccines indicated that they led to antibody production in volunteers.
Gamaleya Research Institute
Name: Sputnik V
Status: Phase 3, approved in Russia, Belarus, and Argentina
The vaccine from Russia’s Gamaleya Research Institute uses two different strains of adenoviruses to carry the genetic sequence for the SARS-CoV-2 spike protein, in two doses separated by three weeks. This strategy is intended to prevent the immune system from learning to recognize the delivery virus and produce antibodies that attack it before it can deliver its genetic payload. A freeze-dried version of the vaccine can be stored in standard refrigerators.
The vaccine received limited approval in Russia in August, before phase 3 trials had even started. In September, published results from small early-stage trials indicated that Sputnik V prompted an immune response. President Vladimir Putin announced the beginning of a large-scale vaccination campaign in early December. The vaccine’s developers reported on December 14 that it was 91.4 percent effective based on data that would be published (but hasn’t yet) in a peer-reviewed journal. So far, Argentina has been the only country to roll out the vaccine.
In October, Russia announced regulatory approval of a second vaccine before phase 3 trials had started. The protein-based vaccine, known as EpiVacCorona, was developed by the state’s Vector Institute. Countries like India, Bolivia, and Algeria have expressed interest in buying doses once they’re more widely available.
Status: Phase 3, emergency use in India
India’s Bharat Biotech started phase 3 trials for its COVID-19 vaccine candidate in November. The company has applied for emergency use authorization with the Drugs Controller General of India. The vaccine, which was developed in partnership with the Indian Council of Medical Research – National Institute of Virology, is given in two doses. It includes an inactivated form of the virus and an adjuvant. The company has not yet released data from its Covaxin trials, although it has said that it is aiming for the vaccine to be at least 60 percent effective. The Indian government granted the company emergency use authorization on January 3.
Status: Phase 2
Inovio, which is headquartered in Pennsylvania, has developed a DNA vaccine that can be stored at room temperature for more than a year. The vaccine is injected into the skin via a handheld device that uses electrical pulses to briefly open small pores in cells so the genetic material can enter more easily.
The FDA put a partial hold on Inovio’s vaccine testing in September to gather more information about the delivery device. In November, the company was cleared to proceed with phase 2 testing in the United States. Inovio has stated that it “plans to resolve the remaining device questions during the conduct of Phase 2 segment and prior to the start of the Phase 3 segment of the trial.” Inovio also began a second phase 2 clinical trial for the vaccine candidate in China in December.
Status: Phase 2/3
CureVac, a biopharmaceutical company headquartered in Germany, is testing an mRNA vaccine candidate that can be refrigerated for at least three months, which could make it easier to roll out than other mRNA vaccines that must be kept at colder temperatures. CureVac’s CVnCoV vaccine is given in two doses of 12 micrograms—a smaller amount than those found in the Moderna and Pfizer mRNA vaccine candidates, which could also make it easier to distribute quickly.
On December 14, the company announced that it had started enrolling people in a combined phase 2/3 clinical trial of its vaccine candidate. In earlier trials, participants produced similar levels of antibodies to people who’d recovered from severe COVID-19. CureVac probably won’t apply for approval of its vaccine candidate until the middle of 2021, the Financial Times reported. The company is collaborating with Tesla, Elon Musk’s electric car company, to make mobile molecule printers that Musk has described as “mRNA microfactories.”
Anhui Zhifei Longcom Biologic Pharmacy and the Chinese Academy of Medical Sciences
Status: Phase 3
The ZF2001 vaccine includes a portion of the SARS-CoV-2 spike protein. The vaccine, which is given in three doses, proceeded to a phase 3 trial in December.
The Chinese Academy of Medical Sciences has also created a vaccine from an inactivated form of the novel coronavirus. This candidate also reached phase 3 trials in December, and is given in two doses. In the first round of results, up to 97 percent of the subjects that received the vaccine developed antibodies.
Sanofi and GlaxoSmithKline
Status: Phase 1/2
The French pharmaceutical company Sanofi and Britain’s GlaxoSmithKline have developed a vaccine that includes adjuvants and SARS-CoV-2 proteins produced inside insect cells. Sanofi has previously used this strategy in its Flublok vaccine for seasonal influenza.
The US has secured 100 million doses of the COVID-19 vaccine, which received funding from the government’s Operation Warp Speed initiative. However, the companies announced disappointing results from their phase 1/2 trial on December 11. In adults between the ages of 18 and 49, the vaccine prompted the immune system to create antibodies against SARS-CoV-2 at comparable levels to those seen in people who recovered from COVID-19. But the immune response was weaker in older adults, indicating that the vaccine dose was too low. Instead of moving into a phase 3 trial in December, the companies plan to start a new phase 2 trial in February with a different formulation of the vaccine. This delay means that the vaccine is unlikely to become available before late 2021.
GlaxoSmithKline is also collaborating with the Canadian biopharmaceutical company Medicago on a different COVID-19 vaccine candidate. It moved into a phase 2/3 clinical trial on November 12, after Medicago reported that it led to antibody production in all healthy volunteers in a phase 1 trial. The CoVLP vaccine is given in two doses three weeks apart. It’s formulated from adjuvants and proteins produced in the leaves of a plant related to tobacco that have had viral genes introduced into them.
Murdoch Children’s Research Institute
Name: Bacillus Calmette-Guérin
Status: Phase 3
The BCG vaccine was created in the early 20th Century to prevent tuberculosis and is given to more than 100 million children around the world every year. To invent the BCG vaccine, French scientists cultured a strain of tuberculosis bacteria from cow udders for years until it was weak enough to cause an immune response without making people ill.
The vaccine has additional benefits beyond protecting people from tuberculosis. In the US, it’s FDA-approved to treat bladder cancer. It may also prime the immune system to ward off other infections. Scientists in California recently reported that the health care workers who received the BCG vaccine in the past were less likely to contract COVID-19. Researchers in Australia are conducting a phase 3 clinical trial to investigate whether the vaccine can protect health care workers from the virus.
Status: Phase 2/3
The Japanese biopharmaceutical company AnGes started a phase 2/3 trial for its COVID-19 vaccine candidate in December. The company has partnered with Osaka University and Takara Bio to produce the DNA-based vaccine, which is given in two doses.
Status: Phase 3
This vaccine candidate, being developed by the Indian vaccine-maker Zydus Cadila, is designed to be delivered via a skin patch. The company finished a Phase 2 trial at the end of December, and announced it had been given the okay to move on to Phase 3. The company has said it could have the candidate ready for widespread use by March 2021.