The first COVID-19 vaccine candidate was administered during a clinical trial in March 2020, a triumph shared worldwide by all those working to overcome the deadly virus. A year later, there are almost 100 vaccines being tested in human trials, including new approaches to immunization whose development has been accelerated by the pandemic. Researchers are now working not just to prevent COVID-19 infections, but to prevent reinfection and address emerging variants as well.
Below, The Scientist rounds up those vaccine candidates that have advanced to clinical trials.
Editor’s note: The introduction of this story was updated on April 15, 2021.
Table updated June 18, 2021. New material highlighted in red.
|VACCINES THAT HAVE RECEIVED APPROVALS|
BioNTech and Pfizer
Four RNA vaccine candidates are being tested in parallel.
Results from a Phase 3 trial published in December 2020 point to 95 percent fewer symptomatic COVID-19 cases among vaccinated individuals compared with placebo-injected controls. In vitro studies published in February 2021 found that the vaccine was effective against mutations in new variants including B.1.351, first detected in South Africa, and B.1.1.7, first spotted in the UK. Other findings that month from a nationwide vaccination program in Israel indicate that the vaccine was 46 percent effective at preventing disease 14 to 20 days after the first dose and 92 percent effective at 7 days after the second shot. In March 2021, the company announced results from its Phase 3 trial indicating that the vaccine is 100 percent effective in children aged 12–15. In a nationwide study published in May 2021 in The Lancet, Israeli researchers reported that two doses of the vaccine provided more than 95 percent protection against infection, hospitalization, severe illness, and death, even among the elderly. On the same day, a study in the NEJM reported that the vaccine is protective against variants B.1.1.7 and B.1.351. A preprint posted in May 2021 reports that both the Pfizer and AstraZeneca vaccines are highly effective against the variant spreading in India after two doses, although both were only 33 percent effective after one shot. In late May 2021, the group released additional data from the Phase 1/2 trial of its mRNA vaccine BNT162b2, the first to be approved for emergency use during the pandemic. The new study, published in Nature, shows that the vaccine continues to generate a robust antibody response up to 85 days after the first dose and that the vaccine is cross-reactive against newly emergent strains. The report further characterizes T cell responses, including the first identification of epitopes recognized by CD8+ T cells induced by a COVID-19 vaccine.
Late stage trials are ongoing in the US, Germany, Brazil, South Africa, China, and other countries. In March 2021, the company announced that a Phase 1/2/3 trial is underway to test the vaccine in children aged 6 months to 11 years. On February 18, 2021, the company announced that a Phase 2/3 trial in pregnant women has commenced in the US. In December 2020, the World Health Organization granted the vaccine WHO’s first emergency use validation. On February 25, 2021, the company announced that participants from the Phase 1 trial will be offered a booster shot as part of study to determine the effectiveness of a third dose against virus variants. In addition, the company says it is working on developing a modified mRNA vaccine aimed at variants. In April 2021, Pfizer announced that people will “likely” need a booster within one year of receiving their first two doses. As of April 2021, Bahrain, Brazil, New Zealand, Saudi Arabia, Switzerland have approved the vaccine for full use, while 40+ countries and the EU have approved it for emergency use. In May 2021, the US FDA amended the vaccine’s emergency use authorization (EUA) to include children as young as 12. Days before, the company submitted its full approval application for individuals 16 or older in the US. In May 2021, Spain approved Pfizer as a second shot for people under 60 who received AstraZeneca as their first shot. Also in May, the company announced a new trial for fully vaccinated adults over 65 who will receive a third, booster shot combined with Pfizer’s pneumococcal conjugate vaccine (20vPnC) candidate. In June 2021, a study in Nature found that the sera of vaccinated individuals neutralized several variants, including delta and eta, while another, published in JAMA Network Open, found that one dose of the vaccine resulted in a 51 percent reduction in the risk of infection after 13 to 24 days. Also in June, Brazil approved the vaccine for children over 12.
Moderna and the US government
Lipid nanoparticles containing mRNAs for the SARS-CoV-2 spike protein are injected into the arm.
Preliminary results from studies on older adults and those under age 55 suggest that the vaccine is safe and elicits higher levels of SARS-CoV-2 antibodies than does infection with the virus, and data from the Phase 3 trial suggest that it is nearly 95 percent protective, the company announced at the end of November. A third study finds that vaccinated monkeys quickly cleared the virus. Moderna is developing similar vaccines against Zika and other viruses, but to date, no vaccine of this type has been approved for use. In May 2021, Moderna announced interim results regarding its booster trials. A third dose of either the current shot or a new candidate both increased immunity against variants first found in Brazil and South Africa.
Phase 1, Phase 2, and Phase 3 clinical trials are underway across the US, and in December, 2020, the company announced that it would begin to test the vaccine on adolescents 12 years and older. On February 24, 2021, the company announced it has commenced Phase 1 trials to test the effectiveness of three different types of booster shots against new virus variants. In March 2021, the company announced a Phase 2/3 trial is underway in the US and Canada to test the vaccine in children aged 6 months to 12 years. As of June 2021, the vaccine is approved for full use in Switzerland and is approved for emergency use in 20+ countries and the European Union. It has also received EUA from the WHO.
Johnson & Johnson’s Janssen division
Nonreplicating adenovirus 26 (Ad26) vector carrying undisclosed genetic material of SARS-CoV-2 is delivered via intramuscular injection.
In late September 2020, the company posted a preprint with preliminary results from an early-stage trial that showed a single dose of the vaccine to be safe and to elicit neutralizing antibodies in nearly all study participants. In January 2021, the company announced results from its Phase 3 study showing that the vaccine is 66 percent effective overall, including participants in the US, Latin America, and South Africa (where the B.1.351 variant is widely circulating). The company is also developing other Ad26-based vaccine candidates, including its Ebola vaccine that was deployed in Democratic Republic of Congo in November 2019.
Early stage clinical trials are underway in the US, Belgium, and Japan, and a Phase 2 trial is ongoing in Spain, Germany, and the Netherlands. Meanwhile, an international Phase 3 trial is underway in the US, Mexico, several South American countries, the Philippines, South Africa, and Ukraine. In mid-November, the company announced a second global Phase 3 trial that would test two doses of the vaccine instead of one. On April 13, the FDA and CDC recommended an immediate pause in the vaccine’s use after six women developed rare blood clots, the same as those considered to be an extremely rare side effect of AstraZeneca’s COVID-19 vaccine. In April 2021, both the EU’s European Medicines Agency and the US FDA said that vaccinations can continue after a pause to examine rare blood clots. On April 26, South Africa resumed efficacy studies of the vaccine. The FDA will be adding a warning about potential blood clot risks to fact sheets issued to providers and patients. The CDC’s federal advisory committee, which previously said it would need more time to study the clots, will release an analysis in early May in its in-house journal, Morbidity and Mortality Weekly Report. On April 27, the Republic of Ireland agreed to make the Johnson & Johnson vaccine available to people under 50 if no other vaccine is available. Both Denmark and Finland announced in May 2021 that they would cease administering the Johnson & Johnson vaccine over concerns about rare blood clots. Also in May, US health officials confirmed a total of 28 cases of blood clots linked to the vaccines, and Belgium temporarily suspended the use of the vaccine in adults under age 41 following a woman’s death. In June 2021, a study in Nature found that the J&J vaccine continues to elicit robust T cell responses against the alpha and beta variants, even if the variants evade neutralizing antibodies generated by the vaccine. The US FDA announced June 11, 2021, that Johnson & Johnson would need to discard roughly 60 million doses manufactured at the same Baltimore factory responsible for prior safety lapses. As of June 2021, the vaccine has been approved for EUA by more than 20 countries, the EU, and the WHO.
CanSino Biologics and the Academy of Military Medical Sciences
China, Canada, Russia, and Saudi Arabia
Nonreplicating adenovirus 5 (Ad5) vector carrying the gene for the SARS-CoV-2 spike protein is injected into the arm.
Preliminary results from the Phase 2 trial published in The Lancet in July suggest that the vaccine is safe and elicits an immune response, either a T cell response or an antibody response. Adenoviruses are well-established vaccine vectors, and CanSino produced an Ebola vaccine (approved in China in 2017) using the same Ad5 platform.
Phase 1 and Phase 2 clinical trials are underway in Wuhan, China. A Phase 1/2 study is underway in Canada, while Phase 3 trials are ongoing in Saudi Arabia as well as in Mexico, Chile, Russia, Pakistan, and Argentina. In June 2020, following positive Phase 1 data published in The Lancet in May, China’s Central Military Commission approved the vaccine’s use by the country’s military for a year. In February 2021, the country approved it for widespread use, as did Mexico and Pakistan. In March 2021, Hungary approved the vaccine for emergency use.
University of Oxford and AstraZeneca
A chimpanzee adenovirus vaccine vector (ChAdOx1) carrying the gene for the SARS-CoV-2 spike protein is injected into the arm.
Preliminary results from the Phase 1/2 trial of people up to 55 years old published in The Lancet in July 2020 suggest that the vaccine is safe and elicits strong antibody and T cell immune responses, and preliminary results from a Phase 2 study published in The Lancet in November finds similar results for older individuals. Preliminary results from the Phase 3 study showed the vaccine to be 70 percent effective on average, according to results published in December in The Lancet, with one and a half doses being more effective than two doses. According to a study published in The Lancet in February 2021 summarizing data on subsets of participants, a single dose is 76 percent effective for up to three months post-vaccination, and a second dose given three months or more after the first dose boosts that efficacy to more than 82 percent. The vaccine appears to be far less effective against the B.1.351 variant circulating in South Africa, according to a yet-to-be-published analysis released on February 7, 2021. A Phase 1 trial using the same adenovirus vector to target MERS is ongoing in Saudi Arabia. A preprint released in May 2021 reported that both the Pfizer and AstraZeneca vaccines are highly effective against the variant spreading in India after two doses, although both were only 33 percent effective after one shot.
Clinical trials at various stages are underway around the globe, with expansion to more countries expected. Researchers in the UK will also test an inhaled form in an early-stage trial. In February 2021, the developers announced that they would begin a Phase 2 trial to test children as young as six years old. In early March 2021, the vaccine was suspended in several European countries due to concerns over blood clots, but resumed again after health authorities ruled the vaccine was safe. Later that month, Germany and Canada suspended the vaccine for use in people under age 60 and 55, respectively. In April 2021, Denmark became the first country to cease administering the AstraZeneca vaccine entirely amid concerns over rare blood clots. The European Union filed a lawsuit against the company in April 2021 for breach of contract after delays in shipping hundreds of millions of doses. On April 27, the Republic of Ireland announced that it will make the AstraZeneca vaccine available to people over 50. Currently, it is only available to those over 60. The vaccine was temporarily suspended in some European countries earlier in 2021, but has since resumed, although Germany and Canada have restricted the vaccine’s use in people under age 60 and 55, respectively.South Africa halted the vaccine’s use after it was shown to less effective against the country’s B.1.351 variant. As of May 2021, the vaccine has been approved for full use in Brazil and for emergency use by more than 70 countries plus the European Union and the World Health Organization. Denmark is the only country to have stopped its use entirely over concerns about blood clots. In May 2021, the Financial Times reported on the results of a yet-unpublished study that found the Oxford-AstraZeneca vaccine is an effective third booster shot that may also be able to protect against new variants.
China, Brazil, Bangladesh, and Indonesia
Results from the Phase 1/2 trial published in The Lancet Infectious Diseases in November 2020 suggest that the vaccine is safe and elicits an antibody-based immune response, although antibody levels were lower than in patients who have been infected and recovered. In January 2021, officials in Brazil announced results suggesting that the vaccine is 78 percent effective, though updated findings released the following week pointed to an efficacy rate of closer to 50 percent, The New York Times reports. Phase 3 trials indicate that the vaccine is 83.5 percent effective at preventing disease, a revision from an earlier finding of 91.25 percent, Reuters reports. In March 2021, the company announced preliminary results that the vaccine is safe for children as young as three years old, according to the AP. Sinovac had used a similar platform to develop a vaccine against SARS in 2004 that showed promising results in early-stage human trials. A new study undertaken by China’s health ministry found that when administered to 120,000 Indonesian healthcare workers, the Sinovac vaccine was 98 percent effective at preventing death, 96 percent effective at preventing hospitalization, and 94 percent effective at preventing symptomatic cases.
A Phase 1/2 clinical trial is underway in China, and Phase 3 trials are ongoing in Bangladesh, Indonesia, and Turkey. A trial is also underway in Brazil. China approved the vaccine’s emergency use for high-risk individuals in July, and for widespread application in February, following regulatory greenlights in Indonesia and Turkey. As of March, the vaccine has received emergency use authorization in at least a dozen countries and from the WHO.
Wuhan Institute of Biological Products and China National Pharmaceutical Group (Sinopharm)
China and United Arab Emirates (UAE)
In mid-June, Sinopharm announced that nearly all of the more than 1,000 participants who had received two injections of the mid-dose vaccine tested positive for antibodies against SARS-CoV-2. In August, Phase 1/2 trial results published in JAMA indicated that the vaccine is safe and elicited neutralizing antibodies. In December, the UAE’s Ministry of Health and Prevention announced that an interim analysis the ongoing Phase 3 trial suggests that the vaccine is 86 percent effective.
A Phase 1/2 clinical trial is underway in China. A Phase 3 trial is underway in UAE, and another is underway in Peru. In December, the UAE approved the vaccine for emergency use, and China approved the vaccine’s widespread use in February.
Beijing Institute of Biological Products and China National Pharmaceutical Group (Sinopharm)
The two-dose vaccine protects rhesus macaques against SARS-CoV-2, according to a paper published in Cell in early June. In mid-October, Sinopharm published results from the early trials in The Lancet showing that the vaccine was safe and that participants receiving the vaccine had high titers of antibodies. Sinopharm has said that interim data suggest the vaccine is 79 percent effective in preventing the disease, according to Reuters, a finding that has since been supported by the WHO, which reported an efficacy rating of 78 percent.
A Phase 1/2 clinical trial is underway in China, which granted the vaccine full approval at the end of December, as did UAE and Bahrain. Phase 3 trials are proceeding in Peru, Morocco, UAE, Egypt, and other countries, and Egypt and Jordan have so far granted approval for emergency use. In April 2021, Indonesia approved the vaccine for emergency use. Sinopharm is the third company to have a COVID-19 vaccine authorized for use in the country. In May 2021, the World Health Organization granted the vaccine EUA, even as it expressed “very low confidence” in the data provided by the company that detailed possible side effects. Its approval means that the vaccine will be rolled into the Covax initiative that provides free vaccines to poor countries.
Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation, Acellena Contract Drug Research and Development
Russia and United Arab Emirates (UAE)
Adenovirus vector displaying the SARS-CoV-2 spike protein on its surface
Preliminary results from the early stage trial published in September in The Lancet point to the Sputnik V vaccine candidate’s safety and ability to elicit an antibody response. In January, also in The Lancet, Gamaleya published preliminary results from the ongoing Phase 3 trial that suggest the vaccine is more than 90 percent effective—a statistic that attracted criticism after it was first announced in November. In May 2021, Russian authorities announced that the one-dose Sputnik Light vaccine had an efficacy of 79.4 percent, enough to use without a second injection. In May 2021, a study conducted by researchers in Argentina found that the Sputnik V vaccine induced 85 percent of recipients to generate antibodies against the Brazilian variant, P.1, two weeks after one dose. After two doses, that number jumped to more than 99 percent.
Phase 1/2 clinical trials are underway in Russia to test liquid and powder forms of the vaccine, while additional trials are being conducted in Belarus, Venezuela, UAE, and India. In August, Russian President Vladimir Putin said that the country approved the vaccine ahead of a Phase 3 trial. Following Sputnik V’s approval for use in India in April 2021, the Russian Direct Investment Fund stated that six dozen countries have now okayed its use. In January 2021, the company began testing a one-dose version of its Sputnik V vaccine using the same adenovirus found in the Johnson & Johnson vaccine. This new candidate is called Sputnik Light, and has since moved into a Phase 3 trial. In May 2021, Sputnik Light was authorized for use in Russia. Days later, Bahrain granted the shot emergency use authorization, with Venezuela expected to do the same. In June 2021, Russia announced that it is testing a nasal spray version of its Sputnik V vaccine in children between the ages of 8 and 12.
Results from a Phase 1 trial indicated that two intramuscular injections of the vaccine, known as BBV152, was well tolerated and elicited no serious adverse side effects. Interim results from a Phase 2 trial also found that the vaccine was safe and induced good antibody and T cell levels. Additional studies are needed to evaluate immune responses in children and people over 65 years old.
State Research Center of Virology and Biotechnology “Vector”
Peptide-based vaccine based on a platform developed for an Ebola vaccine candidate
Volunteers in the Phase 2 trial are “feeling good,” the Russian consumer safety watchdog Rospotrebnadzor said in a statement, according to Reuters.
Clinical testing was completed by the end of September, according to Reuters. In October, Russian President Vladimir Putin announced its approval ahead of a Phase 3 trial, NPR reports, and on November 30, Reuters reported that the country will begin mass vaccinations.
Chumakov Center at the Russian Academy of Sciences
According to Reuters, no adverse effects of the vaccine, known as CoviVac, were observed in participants of an early-phase trial.
Research Institute for Biological Safety Problems
According to a government website, preliminary results from Phase 1 and 2 trials of the QazVac vaccine indicate it is 96 percent effective.
Shafa Pharmed Pars
Preclinical studies in mice, rabbits, and nonhuman primates showed that the vaccine elicited a high level of SARS-CoV-2–specific neutralizing antibodies. The 30 participants experienced no side effects from the first dose of the vaccine, called COVIran Barekat, in the Phase 1 trial.
|ADDITIONAL VACCINES IN CLINICAL TRIALS|
Liquid oral vaccine
The vaccine, called CoV2-OGEN1, is stable at room temperature and does not require a medical professional to be administered.
A Phase 1 trial will begin in June.
Academy of Military Medical Sciences, Suzhou Abogen Biosciences, and Walvax Biotechnology
The vaccine, called ARCoV, produced positive results in preclinical studies using mice and macaques.
A Phase 1 trial is underway in China.
Lanzhou Institute of Biological Products, Beijing Zhong Sheng Heng Yi Pharmaceutical Technology, Zhengzhou University
Recombinant SARS-CoV-2 being grown in Chinese hamster ovary cells
A Phase 1/2 trial is underway in China.
Recombinant protein vaccine based on the receptor-binding domain of SARS-CoV-2’s spike protein
A Phase 1/2 trial is underway in China.
The candidate, EXG-5003, is a self-replicating RNA vaccine expressing the receptor-binding domain of the SARS-CoV-2 spike protein.
A Phase 1/2 trial launched in Japan in April 2021.
Shenzhen Kangtai Biological Products
China & US
After previously working with AstraZeneca to produce its vaccine, Kangtai announced a Phase 1 clinical trial of its own vaccine candidate in October 2020. The vaccine progressed to a Phase 2 trial in February 2021, and a Phase 3 trial is registered to begin in May 2021. The company announced in May 2021 that the Chinese government has approved the vaccine for emergency use.
A Phase 1 trial is testing the safety of the vaccine at two different doses
A synthetic protein fuses the SARS-CoV-2 receptor-binding domain of the spike protein to the crystallizable fragment (Fc) domain of the antibody immunoglobulin G to generate a chimeric protein.
US-based Akston Biosciences’s vaccine candidate, AKS-452, prompts T cells to target the receptor-binding domain on the SARS-CoV-2 spike protein. In a study, nonhuman primates were protected from infection with SARS-CoV-2 following immunization.
A Phase 1/2 clinical trial began in April 2021.
Finlay Vaccine Institute
Recombinant receptor-binding domain of the SARS-CoV-2 spike protein that also contains bacterial proteins and aluminum hydroxide as adjuvants
The vaccine candidate, Soberana Plus, will be given to patients who have recovered from COVID-19, a first of its kind effort to prevent reinfection by emerging variants. A Phase 1 trial induced a strong immune responses in convalescent patients, according to Cuba’s Regulatory Authority of Medicines, Equipment and Medical Devices
Soberana Plus received approval to launch a Phase 2 clinical trial in April 2021.
Walter Reed Army Institute of Research
Nanoparticles studded with the SARS-CoV-2 spike protein created using ferritin, an iron storage protein that self-assembles into spheres
Walter Reed’s two-dose vaccine candidate, SpFN, induced a potent and broadly neutralizing antibody response against the initial strain of SARS-CoV-2, two emergent variants, and SARS-CoV-1 in monkeys.
A Phase 1 clinical trial was launched in April 2021.
A vaccine designed using SARS-CoV-2 epitopes, small fragments of proteins that are recognized by the immune system’s T cells.
CoVepiT is a “multi-target multi-variant” vaccine that activates T cell defenses by targeting 11 different SARS-CoV-2 proteins. These proteins were chosen based on their low rate of mutation, making them less likely to spawn new variants. Positive preclinical results were reported in August 2020, with the candidate vaccine eliciting T cell responses with long-term protective immunity in the respiratory tract and lung of humanized mice and human cells.
A Phase 1 trial is underway in Belgium.
A Phase 1/2 clinical trial is currently underway.
US and South Korea
A special device administers spike protein–encoding DNA molecules through the skin.
Mice and guinea pigs mounted immune responses against the virus, according to a recent preprint, and the company announced interim results from the Phase 1 trial at the end of June that suggested the vaccine was safe and spurred immune responses in 94 percent of the 36 participants analyzed.
Phase 1 and Phase 2/3 clinical trials are ongoing in the US. A Phase 1/2 study is also underway in South Korea. The Phase 3 trial of this vaccine is on hold while the FDA seeks more information about the device used to administer the injection, Reuters reports.
Shenzhen Geno-Immune Medical Institute
Immune cells (human dendritic cells and T cells, or artificial antigen presenting cells) are engineered to express a synthetic minigene based on SARS-CoV-2 proteins and injected or infused into the patient.
The research institute modifies cells using lentivirus vectors that it has used to develop CAR T cell therapies as well as gene therapies.
The vaccine delivers pieces of the SARS-CoV-2 spike protein.
The company announced in December that the vaccine candidate, in combination with adjuvants, was safe and induced neutralizing antibodies and cell-mediated immunity—results that were also posted as a preprint. The Trimer-Tag platform used is the basis for other viral vaccines in development.
Australia and South Africa
Nanoparticles carrying antigens derived from the SARS-CoV-2 spike protein (with Matrix-M adjuvant)
In 2012, the company started development on a SARS vaccine that served as the basis for its new SARS-CoV-2 vaccine candidate. Data from the Phase 1/2 trial published in The New England Journal of Medicine in early September 2020 show the vaccine candidate, known as NVX-CoV2373, to be safe and elicit neutralizing antibody levels greater than those provided by treatment with COVID-19 convalescent serum. In March 2021, the company announced results from Phase 3 trials in the UK and South Africa. UK results indicate that the vaccine is more than 96 percent effective at preventing mild and severe disease against earlier strains of the virus, but it is about 86.3 percent effective against preventing disease from the highly transmissible B.1.1.7 variant. The South African trial found that it was only about 46.3 percent effective at preventing disease from the B.1.351 variant. In both countries, it was 100 percent effective at preventing severe disease. A study published in May 2021 in the NEJM confirmed that the company’s vaccine protects against variant B.1.351. In June 2021, the company released results from its Phase 3 trial in the US and Mexico, finding that its vaccine was more than 90 percent effective against “predominantly circulating Variants of Concern and Variants of Interest.”
A Phase 1 clinical trial is underway in Australia, and a Phase 2 trial is underway in South Africa. Phase 3 trials are underway in the UK, the US, and India. In May 2021, the company expanded its Phase 3 trials to include children as young as 12. As of June, Novavax is also enrolled in a number of larger, sometimes collaborative initiatives, including a study testing how well its vaccine increases immunity when alternated with other vaccines, such as those from Pfizer or Oxford-AstraZeneca, how well it functions as a booster, and how it works when combined with a seasonal flu shot.
Belgium and Germany
RNA vaccine; details not disclosed
In November, the company announced preliminary data from the ongoing Phase 1 trial that showed the vaccine candidate elicits levels of neutralizing antibodies comparable to levels seen in people who have recovered from serious COVID-19 illness and also appears to trigger the production of SARS-CoV-2–fighting T cells, Reuters reports. In June 2021, CureVac released preliminary data from its Phase 2/3 trial, showing that the vaccine had an efficacy of just 47 percent, a finding, the company noted, that “did not meet prespecified statistical success criteria.” The trial will continue.
US and Canada
Virus-like particles that resemble SARS-CoV-2 are produced in a close relative of tobacco.
The company has a rotavirus vaccine in clinical trials that is based on virus-like particles, and another for norovirus in preclinical studies. In May 2021, the company published results from its Phase 1 trial in Nature Medicine. Participants who received two doses of the vaccine, called CoVLP, combined with an adjuvant called AS03 produced neutralizing antibodies at levels 10 times higher than those seen in patients recovering from COVID-19.
Phase 1 trials were first launched in the US and Canada, and Phase 2/3 trials are currently underway in the US, Canada, the UK, and Brazil, with planned expansions into Latin America and Europe. In March 2021, a Phase 3 trial began in the US and Canada.
An adenovirus-vector vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein is delivered intranasally.
A preprint published in October suggests the vaccine elicits immune responses against the RBD in mice. The company is using the same technology to develop a flu vaccine that is in clinical trials.
A Phase 1 trial is underway
AnGes, Japan Agency for Medical Research and Development
Engineered circular DNA encoding the SARS-CoV-2 spike protein
The vaccine consists of two intramuscular injections.
A patient’s own dendritic cells are modified to carry SARS-CoV-2 antigens and then reinfused.
Antigen-carrying dendritic cells triggered a response in the same patient’s lymphocytes in vitro.
A Phase 1/2 trial has been approved to begin in California.
DNA encoding the SARS-CoV-2 spike protein
The vaccine was shown to produce neutralizing antibodies in nonhuman primates.
Phase 1/2 trial underway in South Korea
Recombinant SARS-CoV-2 spike protein plus a polysaccharide adjuvant
In April 2021, the company released early results from their preclinical studies and a Phase 1 trial, finding no major adverse effects and confirming the vaccine’s ability to induce humoral and cellular immune responses in mice, ferrets, monkeys, and humans.
Engineered DNA plasmid encoding a SARS-CoV-2 antigen
In a preclinical study, the vaccine neutralized SARS-CoV-2 in a virus neutralization assay.
Self-replicating mRNA encoding coronavirus proteins
The self-replicating mRNA platform is not the basis of any approved medicines, but preclinical results announced in April suggest the vaccine candidate triggers an immune response.
Sanofi and GlaxoSmithKline (GSK)
Antigen based on SARS-CoV-2 spike protein (with adjuvant)
Sanofi uses the same recombinant DNA technology in a flu vaccine and in a SARS vaccine candidate that never entered clinical trials. Meanwhile, GSK’s adjuvant, AS03, was used in vaccines the company made against the H1N1 and H5N1 pandemic flu viruses. Interim results from the Phase 2 trial showed that the candidate triggered strong neutralizing antibody responses in all adult age groups, and that the vaccine induced a high immune response after a single dose in patients with prior infection, showing potential for the vaccine to be used as a booster.
A Phase 1/2 trial is underway in the US, but after interim results from the study suggested that older participants mounted only weak immune responses, the companies announced a delay in the vaccine’s development timeline, aiming for regulatory submission in the second half of 2021. In February, the companies announced they were starting a new Phase 2 trial, including in older adults. The companies also said they would aim to target new virus variants. After promising results in the Phase 2 trial, the group is now registering participants for a Phase 3 trial.
US and South Africa
A human adenovirus (hAd5) vector delivers SARS-CoV-2 antigens, both the spike protein and the nucleocapsid protein found inside the virus.
The company says it is developing forms of the vaccine for subcutaneous, oral, inhaled, and intranasal administration. Preliminary results from a Phase 1 trial testing the subcutaneous version found a low dose to be safe, the company announced in November. A month later, a macaque study posted as a preprint showed that a combination of the subcutaneous and oral formulations to be safe and protective against a SARS-CoV-2 challenge.
Institute of Microbiology at the Chinese Academy of Sciences and Anhui Zhifei Longcom Biologic Pharmacy Co.
Recombinant protein vaccine based on the receptor-binding domain of SARS-CoV-2 spike protein
The ZF2001 vaccine is administered as three doses spaced 30 days apart. According to a non–peer-reviewed results in medRxiv, the Phase 1 and 2 trials indicated that the vaccine is safe and elicited immune responses.
West China Hospital of Sichuan University
A portion of recombinant SARS-CoV-2 spike protein
The vaccine candidate was safe and effective in preventing infection with the novel coronavirus in animals including monkeys. The approach has been used to develop other vaccines, such as those against flu and cervical cancer.
Orally administered Bifidobacterium probiotic engineered to carry DNA encoding the SARS-CoV-2 spike protein
In addition to this vaccine currently in human testing, two other candidates for COVID-19 are being developed by Symvivo.
Phase 1 clinical trial underway in British Columbia and Nova Scotia
Kentucky BioProcessing (a biotech owned by British American Tobacco)
SARS-CoV-2 antigens produced by tobacco plants are injected into patients.
Kentucky BioProcessing claims its vaccine candidate has a production time of just six weeks and can be stored at room temperature. The company is conducting a Phase 1 clinical trial for an influenza vaccine candidate that uses the same plant-based technology.
A Phase 1 trial is approved to begin in the US.
Inactivated SARS-CoV-2 particles with high density of spike protein, in combination with two adjuvants
The vaccine candidate, VLA2001, relies on the same technology that the company used to develop its approved Japanese encephalitis vaccine. Researchers reported preliminary results from their Phase 1/2 trial, which included 153 adults aged 18 to 55. More than 90 percent of the participants generated significant levels of neutralizing antibodies, and the trial identified no serious safety concerns.
Phase 1/2 clinical trial underway in the UK; In April 2021, Valneva announced the launch of a Phase 3 clinical trial in the UK. Unlike previous trials, in which half the participants received a placebo, half of the volunteers will receive the experimental vaccine and half will receive AstraZeneca’s vaccine, Vaxzevria. The trial will compare the immune responses elicited by the two vaccines.
Israel Institute for Biological Research
Vesicular stomatitis viruses engineered to carry the SARS-CoV-2 spike protein
Preclinical studies in various animal models showed the vaccine to be safe and to bind to and neutralize SARS-CoV-2. Vesicular stomatitis viruses also form the basis of a newly approved vaccine for Ebola.
A Phase 1/2 trial is underway in Israel.
Vaccine and Infectious Disease Organization at the University of Saskatchewan
A portion of the SARS-CoV-2 spike protein
Protein subunit technology has been used in commercially available vaccines for hepatitis, whooping cough, and more.
A Phase 1/2 trial is approved to begin in Nova Scotia, Canada.
Taiwan and Vietnam
A combination of SARS-CoV-2 spike proteins and an adjuvant
Preclinical studies suggest the vaccine candidate is safe and elicits an immune response.
United Biomedical and COVAXX
Peptide-based vaccine consisting of a SARS-CoV-2 spike protein subunit genetically fused to a single-chain Fc domain of human IgG1, combined with other proprietary peptides
According to a press release, results from the Phase 1 trial indicate that the UB-612 vaccine is safe and elicits high antibody titers.
Two vaccine technologies combined: first, an adenovirus vector carrying the genes for the SARS-CoV-2 spike protein and other antigens; then, an mRNAs coding for the viral antigens
No preclinical data available, according to STAT.
A Phase 1 trial to will be conducted by the National Institute for of Allergy and Infectious Diseases.
Canada and Mongolia
Heat-inactivated plasma from donors with COVID-19 taken as a pill daily for a month
The initial safety test will give volunteers the pill for 15 days.
Phase 1/2 clinical trial underway in British Columbia and Mongolia
A pill containing different SARS-CoV-2 antigens
After testing five different vaccine candidates in animals, the company chose its lead candidate, which generated immune responses after a single dose, for clinical testing. The company has other oral recombinant vaccine candidates that have shown success in clinical trials.
Phase 1 trial underway in California
Proprietary replication-defective gorilla adenoviral (GRAd) vector encodes the SARS-CoV-2 spike protein.
In November 2020, the company announced that the GRAd-COV2 vaccine was well tolerated and induced immune responses in subjects aged 18–55 years.
Institute of Medical Biology at Chinese Academy of Medical Sciences, West China Second University Hospital, Yunnan Center for Disease Control and Prevention
Data from the Phase 1 trial, posted as a preprint on October 6, suggests that the vaccine is safe and elicits an immune response, although levels of neutralizing antibody started to drop after just two weeks.
University of Hong Kong and Xiamen University
China and Hong Kong
A nasal-spray consisting of a genetically weakened form of the influenza virus that has been engineered to produce part of the SARS-CoV-2 spike protein
Preclinical work in mice and hamsters showed reduced lung damage upon infection with SARS-CoV-2 when animals were vaccinated. The vaccine’s developers hope that it will protect against flu at the same time.
German Center for Infection Research
A harmless vector called modified vaccinia ankara (MVA) carries the gene for the SARS-CoV-2 spike protein.
The center previously used this approach to develop a vaccine against MERS.
City of Hope
A synthetic modified vaccinia ankara (sMVA) encoding the SARS-CoV-2 spike and nucleocapsid proteins
Mice that received the vaccine generated high levels of neutralizing antibodies and strong T cell responses against the coronavirus’ spike and nucleocapsid antigens, according to research published in Nature Communications in November.
Phase 1 clinical trial underway in California
Adenovirus vector encoding the SARS-CoV-2 spike
Monkeys vaccinated had no detectable SARS-CoV-2 in the upper respiratory and lung tissue after being challenged with the virus.
Phase 1/2 clinical trial underway in South Korea
SpyBiotech and Serum Institute of India
Proprietary “superglue” technology is used to display the SARS-CoV-2 spike protein on the surface of hepatitis B surface antigen virus-like particles (VLPs)
Hepatitis B VLPs are globally licensed as a vaccine for hepatitis B virus.
Phase 1/2 clinical trial underway in Australia
Biological E. Limited
Protein subunit vaccine using receptor binding domain of the SARS-CoV-2 spike protein with adjuvant; Biological E. Limited licensed the vaccine from Baylor College of Medicine, which designed it after the SARS epidemic in 2002 and recently revived the vaccine in conjunction with Texas Children’s Hospital.
The vaccine candidate is thermostable, which should make it possible to distribute in low-resource settings. Preliminary results from the Phase 1/2 trial, which included 360 patients between ages 18 and 65, found that the candidate was “safe and well tolerated and immunogenic.”
Phase 1/2 clinical trial underway in India; In April 2021, the company announced it was starting a Phase 3 trial. The Biden administration has since said it will fund an expansion of Biological E.’s manufacturing capability to combat the high volume of cases in India.
Recombinant protein vaccine
Preclinical studies yielded positive efficacy and safety results, the company announced, noting that the vaccine is stable in refrigerated conditions.
Phase 1/2 clinical trial underway in Japan
University of Tübingen
Multiple SARS-CoV-2 peptides with adjuvant
Unlike most other COVID-19 vaccine candidates, this one aims to specifically induce a T cell–mediated immune response.
Phase 1 clinical trial underway in Germany
SK Bioscience and the University of Washington School of Medicine and GSK
Recombinant protein vaccine consisting of nanoparticles displaying the receptor binding domain of the SARS-CoV-2 spike protein with an adjuvant of aluminum hydroxide
A preclinical study indicated that the vaccine, known as GBP510, elicited high titers of neutralizing antibodies in mice.
A Phase 1/2 trial is underway in Korea.
Protein subunit vaccine with adjuvant
Preclinical trials showed high safety and efficacy, according to the company’s website. Results from clinical trials are expected in the middle of 2021.
Scientific and Technological Research Council of Turkey
A Phase 1 trial is underway in Turkey.
No serious side effects from Phase 1 trials were reported.
Codagenix and Serum Institute of India (SII)
Single-dose, intranasal, live-attenuated virus
Phase 1 clinical trial underway in the UK
Nanoparticles carrying antigens derived from the receptor binding domain on the SARS-CoV-2 spike protein
A Phase 1/2 trial is currently underway in Australia to test the vaccine’s safety and efficacy as a booster.
SARS-CoV-2 recombinant protein subunit vaccine
According to Korea Biomedical Review, preclinical trials of the vaccine, known as NBP2001, indicated it was safe and elicited strong immune responses in primates.
A Phase 1 trial is underway in Korea
A virus-like particle producing the SARS-CoV-2 spike protein
The company reported that the VBI-2902 vaccine elicited high neutralizing antibody titers in hamsters. Vaccinated animals exposed to the virus also had lower virus replication and reduced lung inflammation.
Icahn School of Medicine at Mount Sinai
A vector using Newcastle disease virus, an avian pathogen that causes little to no symptoms in humans, produces the spike protein of SARS-CoV-2
According to a study published in EBioMedicine, intramuscular injection of the vaccine elicited high levels of antibodies in mice and protected them from infection when exposed to mouse-adapted SARS-CoV-2.
A Phase 1 trial is underway in Thailand.
Takis and Rottapharm Biotech
A DNA plasmid encoding the SARS-CoV-2 spike protein. Delivery of the DNA to cells is enhanced with electroporation, a technique that uses light and electrical stimulation to increase cell membrane permeability
According to the company, preclinical trials showed that the COVID-eVax vaccine is safe and elicits immune responses in animals
A Phase 1/2 trial is underway in Italy.
Razi Vaccine & Serum Research Institute
Recombinant protein subunit vaccine
Researchers are testing the delivery of the Razi Cov Pars vaccine via intramuscular injection and nasal spray.
BioNet-Asia and Technovalia
Asia and Australia
A DNA fragment encoding the SARS-CoV-2 spike protein is delivered to the skin or muscle without a needle.
According to the company, preclinical trials indicate that the vaccine, known as COVIGEN, is safe and elicits immune responses in animals.
A Phase 1 trial is underway in Australia.
A live, attenuated respiratory syncytial virus (RSV) expresses the gene for the spike protein of SARS-CoV-2. The vaccine is administered as drops or a nasal spray.
According to the company, preclinical trials showed that the MV-014 vaccine induced neutralizing antibodies in nonhuman primates and protected the animals from disease after exposure to the virus.
A Phase 1 trial is underway in the US
Iran Ministry of Defense
The vaccine is called FAKHRAVAC.
A Phase 1 trial is underway in Iran.
Center for Genetic Engineering and Biotechnology of Cuba
Recombinant receptor-binding domain of SARS-CoV-2 spike protein with aluminum hydroxide adjuvant
According to a report, Phase 1 trials found that the vaccine, known as Abdala (CIGB 66), is safe and elicits immune responses.
Center for Genetic Engineering and Biotechnology of Cuba
The vaccine uses the SARS-CoV-2 spike protein along with a protein from the Hepatitis B virus (AgnHB).
According to a Cuban news site, Phase 1 trials of the vaccine, known as Mambisa (CIGB 669), which is delivered as a nasal spray, is safe and elicits immune responses.
A Phase 1 trial is underway in Cuba.
Finlay Vaccine Institute
A conjugate vaccine composed of the receptor-binding domain of the SARS-CoV-2 spike protein connected chemically to a modified tetanus protein
The vaccine is known as Soberana-02 or FINLAY-FR-2.
A Phase 3 trial is underway Cuba.
Finlay Vaccine Institute
Recombinant receptor-binding domain of SARS-CoV-2 spike protein
The vaccine is called Soberana-01.
Phase 1/2 trials are underway in Cuba.
Sanofi and Translate Bio
mRNA vaccine carrying the genetic sequence for the SARS-CoV-2 spike protein
Results from preclinical trials showed that the vaccine, known as MRT5500, was safe and elicited high antibody levels in mice and monkeys.
Daiichi Sankyo and University of Tokyo
According to an announcement from the company, preclinical studies found that the vaccine, known as DS-5670, was safe and effective.
In March 2021, the company announced that a Phase 1/2 trial is underway in Japan.
Zhongyianke Biotech, Liaoning Maokangyuan Biotech, and the Academy of Military Medical Sciences
Recombinant SARS-CoV-2 vaccine made within Chinese hamster ovary cells
|VACCINES THAT HAVE BEEN ABANDONED|
A vesicular stomatitis virus (VSV) carries undisclosed viral components
The VSV vector is used for Merck’s existing Ebola vaccine.
A weakened measles virus vector carries undisclosed viral components
Merck is purchasing Vienna-based Themis, which has an existing measles vaccine, to develop the COVID-19 vaccine.
University of Queensland and CSL
Molecular clamp technology presents viral proteins to the immune system.
Preclinical work in cell culture showed that the vaccine candidate elicited an immune response that was capable of neutralizing SARS-CoV-2 infection.
Results of a Phase 1 trial in Australia suggested the vaccine was safe and effective, but because it uses fragments from an HIV protein, some trial participants got false positives on HIV test, so CSL announced in December that it was canceling the project.
Imperial College London
Self-amplifying RNA molecules are injected into the muscle.
The vaccine platform, which is designed to allow researchers to respond quickly to emerging pathogens, received $8.4 million from CEPI last December. “We cannot predict where or when Disease X will strike, but by developing these kinds of innovative vaccine technologies we can be ready for it,” CEPI CEO Richard Hatchett said at the time.
A Phase 1 trial is underway in the UK, but instead of advancing this vaccine candidate to efficacy trials in the UK, the university announced in January that it would focus its efforts on developing booster shots and vaccines that target emerging variants of the virus.
In addition to vaccine candidates specific to SARS-CoV-2, several trials are underway testing vaccines against different pathogens as well as nonspecific formulations designed to stimulate an innate immune response.
The Bacille Calmette-Guerin (BCG) vaccine for tuberculosis consists of live attenuated Mycobacterium bovis.
Lower rates of COVID-19–related deaths in countries with mandatory BCG vaccination prompted the launch of several clinical trials to test whether the immune response triggered by the vaccine may protect against SARS-CoV-2.
Several Phase 3 and 4 trials are underway.
The measles-mumps-rubella (MMR) vaccine consists of live-attenuated strains of the three viruses.
Epidemiological data have revealed that places where the MMR vaccine is given as standard medical care have lower COVID-19 death rates than areas where MMR vaccination is not standard. Additionally, sailors aboard the U
A Phase 3 trial is underway in Egypt, led by researchers at Kasr El Aini Hospital. Separately, researchers at the Washington University School of Medicine are running an international Phase 3 trial of healthcare workers in the US, Canada, Europe, and Africa.
Immunovative Therapies, Mirror Biologics
An off-the-shelf living immune cell
The affiliated companies are currently testing the formulation as a therapeutic vaccine for chemotherapy-refractory metastatic cancers.
A Phase 1/2 trial for healthy older adults has been approved to begin in New York.
Canadian Cancer Trials Group, others
Heat-killed Mycobacterium obuense
The vaccine is intended to stimulate nonspecific innate immunity. The company is also testing the vaccine in clinical trials for cancer.
Bandim Health Project
Oral polio vaccine, an attenuated strain of the poliovirus
Researchers argue that the vaccine is safer and available in greater quantities than the BCG vaccine against tuberculosis, which is also being tested as a possible COVID-19 preventive.
A Phase 4 trial has been approved to begin in Guinea-Bissau in West Africa.
A mixture of inactivated bacteria
The vaccine is intended to stimulate nonspecific innate immunity.
A Phase 3 trial for healthcare workers has been approved to begin in Mexico.
An inhaled combination of two synthetic Toll-like receptor agonists
The vaccine was originally developed as a potential therapeutic for cancer and has undergone early stage clinical testing. In mice, it provided protection against a range of respiratory pathogens, including MERS and SARS.
A Phase 2 trial for people with known SARS-CoV-2 exposure is underway in several US states.
Corrections: An earlier versions of this table stated that Janssen’s adenovirus-based COVID-19 vaccine candidate is administered intranasally. In fact, the vaccine is administered via intramuscular injection. / An earlier version of this table stated that the Phase 1 and Phase 2 Moderna trials were taking place in Seattle. In fact, there have been multiple locations since the Phase 1. / A previous update to this table implied that the adverse event that caused the Phase 3 AstraZeneca trial to be put on hold occurred in the Phase 1/2 trial in the UK. In fact, the event occurred in a participant enrolled in the Phase 3 UK study. / A previous update to this table listed Switzerland as having given emergency use approval for the Pfizer/BioNTech COVID-19 vaccine. In fact, the country granted its full approval. / A previous version of this table indicated that UAE and Bahrain had given emergency approval for the Beijing Institute of Biological Products’s COVID-19 vaccine; in fact, these countries have granted full approval. / A previous version of this table stated that Altimmune’s vaccine was approved for a Phase 2 trial; in fact, it is approved for Phase 1. / A previous version of this table stated that China had approved the Sinopharm vaccine developed by Wuhan Institute of Biological Products in December 2020; in fact, that approval happened in February 2021. The Scientist regrets the errors.