COVID-19 Vaccine Frontrunners
Several vaccine candidates have been approved for early testing in people. Many more are close on their heels.
Jef Akst
Apr 7, 2020
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Early last month (March 3), 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.
See “Newer Vaccine Technologies Deployed to Develop COVID-19 Shot”
The Coalition for Epidemic Preparedness Innovations (CEPI), a nonprofit dedicated to the development of vaccines against emerging infectious diseases, has been one source of cash for this endeavor, with a total of nearly $30 million so far invested in several candidates, including the first to be injected into trial participants. The organization plans to advance the top six of these candidates into larger efficacy trials with thousands of participants.
Another bolus of funds comes from the Biomedical Advanced Research and Development Authority (BARDA), part of the HHS Office of the Assistant Secretary for Preparedness and Response, which is contributing 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 that was injected into the first trial participants last month at the Kaiser Permanente Washington Health Research Institute in Seattle. In their announcement this week, J&J and BARDA said that the funds would be put toward both ushering the potential vaccines through clinical development and setting up manufacturing capacity simultaneously.
See “US Selects Two COVID-19 Vaccine Candidates for Huge Investments”
Below, The Scientist rounds up those vaccine candidates that appear to be furthest along. But there are dozens more in preclinical development, and it’s still very early days. “Nobody knows which vaccines are going to work,” Moderna CEO Stéphane Bancel tells Science last week (March 31).
See “Clinical Trial of COVID-19 Vaccine Begins in Seattle”
Editor’s note: This table was updated on May 27, 2020.
DEVELOPER(S) | VACCINE METHOD | EVIDENCE | STATUS |
Moderna and the US government US | Lipid nanoparticles containing mRNAs for the SARS-CoV-2 spike protein are injected into the arm. | Moderna is developing similar vaccines against Zika and other viruses, and other companies have RNA vaccines in clinical trials as well, but to date, no vaccine of this type has been approved for use. The SARS-CoV-2 mRNA-1273 was not tested in animals before the start of the ongoing Phase 1 trial. | Phase 1 clinical trial underway in Seattle; Phase 2 trial approved |
CanSino Biologics and the Academy of Military Medical Sciences China and Canada | Nonreplicating adenovirus 5 (Ad5) vector carrying the gene for the SARS-CoV-2 spike protein is injected into the arm. | Adenoviruses are well-established vaccine vectors, and CanSino produced an Ebola vaccine (approved in China in 2017) using the same Ad5 platform. The company says its Ad5-nCoV vaccine generated “strong immune responses in animal models” and has “a good safety profile.” | Phase 1 and Phase 2 are clinical trials underway in Wuhan, China. Phase 1 data published in The Lancet on May 22 suggest that a single dose is “tolerable” and can induce a good immune response in some subjects. A Phase 1/2 trial has been approved to begin in Canada. |
University of Oxford and AstraZeneca UK | A chimpanzee adenovirus vaccine vector (ChAdOx1) carrying the gene for the SARS-CoV-2 spike protein is injected into the arm. | Six macaques that had received a single dose of the vaccine candidate stayed healthy after being exposed to SARS-CoV-2. A Phase 1 trial using the same adenovirus vector to target MERS is ongoing in Saudi Arabia. | A Phase 1/2 trial is underway in the UK, and enrollment has begun for a follow-up Phase 2/3 trial. AstraZeneca aims to make 30 million doses available in the UK by September. |
Inovio Pharmaceuticals US | 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 tells Nature that it is now testing the vaccine in monkeys. | Phase 1 trial underway with plans to manufacture 1 million doses of its candidate this year |
Sinovac Biotech China | Inactivated SARS-CoV-2 | In animal studies, the vaccine candidate provides protection against virus strains from different countries. Sinovac had used a similar platform to develop a vaccine against SARS in 2004 that showed promising results in early-stage human trials. | Phase 1/2 trial underway |
Wuhan Institute of Biological Products and China National Pharmaceutical Group (Sinopharm) China | Inactivated SARS-CoV-2 | Studies in monkeys, mice, rabbits, and guinea pigs supported the vaccine candidate’s approval for testing in humans. | Early stage trial underway |
Symvivo Canada | 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 |
BioNTech and Pfizer US | RNA vaccine; details not disclosed | BioNTech and Pfizer are also partnering on an RNA vaccine candidate for influenza. | Phase 1/2 trial underway, and the companies plan to supply millions of vaccines by year end |
Shenzhen Geno-Immune Medical Institute China | 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. | A Phase 1/2 clinical trial is underway for the dendritic cell and T cell–based vaccines, and a Phase 1 trial is underway for a vaccine using artificial antigen presenting cells. |
Multiple organizations International | 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. | |
Novavax Australia | 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. | Phase 1 trial underway in Australia |
CureVac | RNA vaccine; details not disclosed | CureVac reported in January that a Phase 1 trial of a comparable vaccine for rabies induced immune responses with just 1 microgram of mRNA, meaning it could be easy to scale up to produce mass quantities. | Expected to start clinical testing in early summer; company says it could manufacture 10 million doses by that time. |
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 in the next few months |
Janssen | Nonreplicating adenovirus 26 (Ad26) vector carrying undisclosed genetic material of SARS-CoV-2 is administered intranasally. | Janssen is also developing other Ad26-based vaccine candidates, including its Ebola vaccine that was deployed in the Democratic Republic of Congo in November 2019. | Expected to start clinical testing in September 2020; with BARDA’s support, the company will scale up to produce up to 300 million doses of vaccine in the US each year |
Generex Biotechnology | 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 |
Clover Biopharmaceuticals | The vaccine delivers pieces of the SARS-CoV-2 spike protein. | The Trimer-Tag platform used is the basis for other viral vaccines in development. | Expected to start clinical testing in Australia with the firm Linear Clinical Research within two months |
Vaxart | 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. | Expected to start clinical testing early in the second half of 2020 |
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. | Expected to start clinical testing in the summer |
Medicago | 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. | Expected to start clinical testing in July or August |
Altimmune | Undisclosed vaccination delivered intranasally | The company is using the same technology to develop a flu vaccine that is in clinical trials. | Expected to begin clinical testing in August |
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 |
Sanofi and 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. | Expected to start clinical testing in the second half of 2020 |
Merck | 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 |
Merck | 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 |
