In early March, National Institutes of Allergy and Infectious Diseases Director Anthony Fauci stated that it would take at least a year to a year and a half to get a COVID-19 vaccine approved for use in the US, and that estimate may be optimistic, according to some experts. There are many unknowns this early in the game. How the early candidates will perform, which will be advanced to later stages of clinical development, what safety issues might arise, and how a successful vaccine will be mass produced are among the questions that are now getting attention and funding.
The Coalition for Epidemic Preparedness Innovations (CEPI), a nonprofit dedicated to the development of vaccines against emerging infectious diseases, was an early source of cash for this endeavor and has continued to pour money into vaccine development. Another early bolus of funds came from the Biomedical Advanced Research and Development Authority (BARDA), part of the HHS Office of the Assistant Secretary for Preparedness and Response, which contributed hundreds of millions of dollars to two top vaccine candidates: one made by Johnson & Johnson’s Janssen division and another developed by Moderna in collaboration with the US government. The US government’s Operation Warp Speed has also invested heavily, giving more than $1 billion each to Novavax and to AstraZeneca, which is collaborating on a vaccine developed by the University of Oxford, early on in the pandemic, and investing a total of more than $11 billion (including through BARDA) by the end of September, according to Genetic Engineering & Biotechnology News.
Below, The Scientist rounds up those vaccine candidates that appear to be furthest along. But there are many more in preclinical development. “Nobody knows which vaccines are going to work,” Moderna CEO Stéphane Bancel told Science in March.
Editor’s note: This story was updated on November 3 to reflect new developments in funding. The table is regularly updated. New information in bold, red font.
BioNTech and Pfizer
Four RNA vaccine candidates are being tested in parallel.
Preliminary results from the early stage trials suggest that the vaccine is safe and elicits higher levels of SARS-CoV-2 antibodies than infection with the virus, according to two preprints posted by the companies in July, one of which was later published in Nature. A second study published in Nature at the end of September reported that the vaccine generated T cell responses in addition to antibody responses. Final results from the Phase 3 trial published in The New England Journal of Medicine in December point to 95 percent fewer symptomatic COVID-19 cases among vaccinated individuals compared with placebo-injected controls.
Late stage trials are ongoing in the US, Germany, Brazil, South Africa, China, and other countries; in October, the companies announced that the Phase 3 trial would expand to include adolescents 12 years and older. In December, the UK, Bahrain, Canada, the US, Mexico, and the EU approved the vaccine for emergency use, while Saudi Arabia and Switzerland have given it full approval.
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.
Phase 1, Phase 2, and Phase 3 clinical trials are underway across the US, and in December, the company announced that it would begin to test the vaccine on adolescents 12 years and older. On December 18, the FDA green-lighted the vaccine’s emergency use. Less than a week later, Canada’s regulatory agency did the same. In January, the EU, the UK, Israel, and Switzerland also followed suit.
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 Mexico, Chile, Russia, Pakistan, and Argentina. On June 25, following positive Phase 1 data published in The Lancet on May 22, China’s Central Military Commission approved the vaccine’s use by the country’s military for a year.
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 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. A Phase 1 trial using the same adenovirus vector to target MERS is ongoing in Saudi Arabia.
Clinical trials at various stages are underway around the globe, with expansion to more countries expected. On September 9, all ongoing trials were placed on hold after a serious adverse event arose in a participant enrolled in the Phase 3 study in the UK. Three days later, UK trials resumed, and in mid-October, the FDA authorized the restart of the US trial. Researchers in the UK will also test an inhaled form in an early-stage trial. At the end of December, the UK, Argentina, El Salvador, and the Dominican Republic approved the vaccine’s emergency use. In January, India’s, Mexico’s, Nepal’s, Morocco’s, and Thailand’s regulatory agencies did the same.
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.
China, Brazil, Bangladesh, and Indonesia
Results from the Phase 1/2 trial published in The Lancet Infectious Diseases in November 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, officials in Brazil announced results suggesting that the vaccine is 78 percent effective, though updated results released the following week pointed to an efficacy rate of closer to 50 percent, The New York Times reports. Sinovac had used a similar platform to develop a vaccine against SARS in 2004 that showed promising results in early-stage human trials.
A Phase 1/2 clinical trial is underway in China, and Phase 3 trials are underway in Bangladesh, Indonesia, and Turkey. A trial was also underway in Brazil. China approved the vaccine’s emergency use in July, and in January, Indonesia and Turkey approved the vaccine’s emergency use.
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 has been approved to begin in Peru. In December, the UAE and China approved the vaccine for emergency use.
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.
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 shows the vaccine candidate to be safe and elicit neutralizing antibody levels greater than those provided by treatment with COVID-19 convalescent serum.
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 November, Gamaleya announced very early results from the ongoing Phase 3 trial that suggest the vaccine is more than 90 percent effective—a statistic that has attracted criticism but that the research institute said in December was confirmed with another analysis based on final data.
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. In August, Russian President Vladimir Putin said that the country approved the vaccine ahead of a Phase 3 trial. Since late December, the Russian Direct Investment Fund has stated that Belarus, Argentina, Bolivia, Palestine, Algeria, Serbia, Venezuela, Paraguay, Turkmenistan, UAE, and Hungary have also approved its emergency use.
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
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.
Phase 1/2 clinical trial underway in China
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.
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.
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.
Undisclosed vaccination delivered intranasally
The company is using the same technology to develop a flu vaccine that is in clinical trials.
A Phase 2 trial has been approved
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
Vaxine developed an experimental swine flu vaccine during the 2009 pandemic.
Phase 1 trial approved to begin in Australia
Engineered DNA plasmid encoding a SARS-CoV-2 antigen
In a preclinical study, the vaccine neutralized SARS-CoV-2 in a virus neutralization assay.
In guinea pigs and mice, the vaccine was safe and elicited an immune response.
Nonreplicating adenovirus 26 (Ad26) vector carrying undisclosed genetic material of SARS-CoV-2 is delivered via intramuscular injection.
Janssen published preclinical data in Nature in July demonstrating that the vaccine protected monkeys against SARS-CoV-2 infection. In late September, 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. 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. On October 12, the company announced that it had temporarily paused further dosing in all of these trials after a participant developed an unexplained illness, but less than two weeks later, it announced that it was preparing to resume these studies. In mid-November, the company announced a second global Phase 3 trial that would test two doses of the vaccine instead of one.
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.
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.
Proprietary replication-defective gorilla adenoviral (GRAd) vector encodes the SARS-CoV-2 spike protein.
The vaccine candidate was safe and induced an immune response in animal models, according to the company.
Phase 1 trial underway in Italy
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.
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.
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.
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
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
Animal studies showed that the vaccine candidate elicited high levels of neutralizing antibodies. Vaccinated animals had less virus in their lungs and suffered less lung damage, according to iChongqing. In late October, the company announced preliminary data from the ongoing early-stage trials that suggest the vaccine candidate is safe and elicits an immune response, according to China’s State Council.
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.
A Phase 2 trial is set to begin in China, Reuters reported in mid-November.
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 relies on the same technology that the company used to develop its approved Japanese encephalitis vaccine.
Phase 1/2 clinical trial underway in the UK
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
Preclinical studies in multiple animal models suggest the vaccine candidate generates neutralizing antibodies and other immune responses.
A Phase 1 trial is underway in Taiwan.
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.
|NOT YET IN CLINICAL TRIALS|
University of Pittsburgh School of Medicine
Microneedle patch delivers pieces of the spike protein through the skin.
Vaccinated mice produced antibodies specific to SARS-CoV-2 at levels that would likely neutralize the virus, according to a study published in EBioMedicine on April 2.
Expected to start clinical testing within a few months of that publication, according to the university
Undisclosed synthetic viral peptides are combined with proprietary Ii-Key immune system activation
The company has had success with the Ii-Key technology for other infectious diseases and for cancer in clinical trials.
Expected to start clinical testing “within 90 days,” the company announced on February 27
Takis Biotech and Applied DNA Sciences
The company is exploring five DNA-based candidates based on the SARS-CoV-2 spike protein.
The vaccine candidates contain PCR-produced pieces of linear DNA, as opposed to the more traditional circular plasmids, which could have several advantages including quick production. No vaccines using this approach have yet been tested in humans.
Expected to start clinical testing in the fall
A vesicular stomatitis virus (VSV) carries undisclosed viral components
The VSV vector is used for Merck’s existing Ebola vaccine.
Expected to start clinical testing later this year
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.
Expected to start clinical testing later this year
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.
Correction (June 11, 2020): An earlier version 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.
Correction (July 27, 2020): 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.
Correction (September 9, 2020): 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.
Correction (January 18, 2021): 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.
The Scientist regrets the errors.