The absolute risk reduction (ARR), which is the difference between attack rates with and without a vaccine, considers the whole population.
ARRs tend to be ignored because they give a much less impressive effect size than RRRs:
- 1,3% for the AstraZeneca–Oxford,
- 1,2% for the Moderna–NIH,
- 1,2% for the J&J,
- 0,93% for the Gamaleya, and
- 0,84% for the Pfizer–BioNTech vaccines.
So, basically NO PREVENTION. - The only reported indication of vaccine effectiveness is the Israeli mass vaccination campaign using the Pfizer–BioNTech product.
- Coronavirus Vaccine Tracker.
COVID-19 vaccine efficacy and effectiveness—the elephant (not) in the room
Piero Olliaro, Els Torreele, Michel VaillantPublished:April 20, 2021. DOI: https://doi.org/10.1016/S2666-5247(21)00069-0
Depending on how the effect size is expressed, a quite different picture might emerge (figure; appendix).
Although the RRR considers only participants who could benefit from the vaccine, the absolute risk reduction (ARR), which is the difference between attack rates with and without a vaccine, considers the whole population.
ARRs tend to be ignored because they give a much less impressive effect size than RRRs:
1,3% for the AstraZeneca–Oxford,
1,2% for the Moderna–NIH,
1,2% for the J&J,
0,93% for the Gamaleya, and
0,84% for the Pfizer–BioNTech vaccines.
_
For instance, supposing that a well-designed randomised controlled trial in children with a particular disease found that 20 per cent of the control group developed bad outcomes, compared with only 12 per cent of those receiving treatment.
Absolute riskreduction (ARR) - also called risk difference (RD) - is the most useful way of presenting research results to help your decision-making. In this example, the ARR is 8 per cent (20 per cent - 12 per cent = 8 per cent). This means that, if 100 children were treated, 8 would be prevented from developing bad outcomes.
https://www.ncbi.nlm.nih.gov/books/NBK63647/
_
This is not a trivial question because transmission intensity varies between countries, affected by factors such as public health interventions and virus variants.
The only reported indication of vaccine effectiveness is the Israeli mass vaccination campaign using the Pfizer–BioNTech product.
Although the design and methodology are radically different from the randomised trial, Dagan and colleagues report an RRR of 94%, which is essentially the same as the RRR of the phase 3 trial (95%) but with an ARR of 0·46%, which translates into an NNV of 217 (when the ARR was 0·84% and the NNV was 119 in the phase 3 trial).
This means in a real-life setting, 1·8 times more subjects might need to be vaccinated to prevent one more case of COVID-19 than predicted in the corresponding clinical trial.
https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00069-0/fulltext
Download .pdf (.22 MB)
*Everyone please watch this video*
— Patrick Henningsen (@21WIRE) August 23, 2021
The #vaccine manufacturer claims of "95% effective" etc - are a lie laundered by Govt & Media, constituting mass fraud.
⚕️ 💉VIDEO: Everything You Need to Know About Informed Consent – ‘It’s Your Right’ (watch, share) https://t.co/vXq50VWrXX pic.twitter.com/99E2xDrg7f
This clip shows *according to their own data* how little overall benefit there actually is to the Pfizer vaccine. pic.twitter.com/wvJ9Uq0A9D
— N U A N C E (@net_nuance) August 23, 2021
__
References
- 1.Covid-19 Vaccine Tracker.https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.htmlDate accessed: March 10, 2021
- 2.Safety and efficacy of the BNT162b2 mRNA COVID-19 Vaccine.N Engl J Med. 2020; 383: 2603-2615
- 3.Efficacy and safety of the mRNA-1273 SARS-CoV-2 Vaccine.N Engl J Med. 2021; 384: 403-416
- 4.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.Lancet. 2021; 397: 99-111
- 5.Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia.Lancet. 2021; 397: 671-681
- 6.Vaccines and Related Biological Products Advisory Committee meeting: FDA briefing document.https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-december-10-2020-meeting-announcementDate: Dec 10, 2020Date accessed: March 10, 2021
- 7.Vaccines and Related Biological Products Advisory Committee meeting: FDA briefing document.https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-december-17-2020-meeting-announcementDate: Dec 17, 2020Date accessed: March 10, 2021
- 8.Vaccines and Related Biological Products Advisory Committee meeting: FDA briefing document.https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-february-26-2021-meeting-announcementDate: Feb 26, 2021Date accessed: March 10, 2021
- 9.What does 95% COVID-19 vaccine efficacy really mean?.Lancet Infect Dis. 2021; (published online Feb 17.)
- 10.Outcome reporting bias in COVID-19 mRNA vaccine clinical trials.Medicina (Kaunas). 2021; 57: 199
- 11.BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting.N Engl J Med. 2021; (published online Feb 24.)
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00069-0&id=gr1.jpg){kind=link}
___
Coronavirus Vaccine Tracker
Carl Zimmer, Jonathan Corum and
PHASE 1
PHASE 2
PHASE 3
AUTHORIZED
APPROVED
ABANDONED
51
37
27
7
8
4
Vaccines
testing safety
and dosage
Vaccines
in expanded
safety trials
Vaccines
in large-scale
efficacy tests
Vaccines
in early or
limited use
Vaccines
approved
for full use
Vaccines
abandoned
after trials
Vaccines typically require years of research and testing before reaching the clinic, but in 2020, scientists embarked on a race to produce safe and effective coronavirus vaccines in record time. Researchers are currently testing 92 vaccines in clinical trials on humans, and 27 have reached the final stages of testing. At least 77 preclinical vaccines are under active investigation in animals.
| New additions and recent updates | |
|---|---|
| May 25 | Pennsylvania-based VaxForm enters Phase 1. |
| May 20 | China’s Stemirna Therapeutics enters Phase 1. |
| May 18 | China authorizes Shenzhen Kangtai’s vaccine for emergency use. |
| May 14 | France’s OSE Immunotherapeutics enters Phase 1. |
| May 10 | The F.D.A. authorizes the Pfizer-BioNTech vaccine for children 12 to 15. |
| May 7 | The W.H.O. gives emergency use authorization to the Sinopharm vaccine. |
| May 6 | Russia authorizes a one-dose version of the Gamaleya vaccine, dubbed “Sputnik Light.” |
| May 5 | China’s Lanzhou Institute of Biological Products enters Phase 1/2. |
| May 3 | Denmark announces it will no longer use Johnson & Johnson’s vaccine. |
| May 1 | Baltimore-based Elixirgen Therapeutics enters Phase 1/2. |
| April 30 | Turkey’s Scientific and Technological Research Council of Turkey enters Phase 1. |
| April 28 | A third vaccine from China’s Sinopharm enters Phase 1/2. |
| April 28 | Kazakhstan begins public use of its QazVac vaccine. |
| April 26 | A vaccine from Baylor College of Medicine and Texas Children’s Hospital moves to Phase 3. |
| April 23 | The European Commission is preparing a legal case against AstraZeneca for failing to deliver enough doses. |
| Leading vaccines | ||||
|---|---|---|---|---|
| Developer | How It Works | Phase | Status | |
  | Pfizer-BioNTech | mRNA | 23 | Approved in several countries. Emergency use in U.S., E.U., other countries. |
| Moderna | mRNA | 3 | Approved in Switzerland. Emergency use in U.S., E.U., other countries. |
 | Gamaleya | Ad26, Ad5 | 3 | Emergency use in Russia, other countries. |
  | Oxford-AstraZeneca | ChAdOx1 | 23 | Approved in Brazil. Emergency use in U.K., E.U., other countries. |
 | CanSino | Ad5 | 3 | Approved in China. Emergency use in other countries. |
 | Johnson & Johnson | Ad26 | 3 | Emergency use in U.S., E.U., other countries. |
| Vector Institute | Protein | 3 | Early use in Russia. Approved in Turkmenistan. |
| Novavax | Protein | 3 | |
| Sinopharm | Inactivated | 3 | Approved in China, U.A.E., Bahrain. Emergency use in other countries. |
| Sinovac | Inactivated | 3 | Approved in China. Emergency use in other countries. |
| Sinopharm-Wuhan | Inactivated | 3 | Approved in China. Limited use in U.A.E. |
 | Bharat Biotech | Inactivated | 3 | Emergency use in India, other countries. |
Below is a list of all vaccines that have reached trials in humans, along with a selection of promising vaccines being tested in animals. For an explanation of virus variants and mutations, see our Coronavirus Variant Tracker. For treatments for Covid-19, see our Coronavirus Drug and Treatment Tracker. For an explanation of leading vaccines, see How Nine Covid-19 Vaccines Work.
The Vaccine Testing Process
The development cycle of a vaccine, from lab to clinic.
PRECLINICAL TESTING: Scientists test a new vaccine on cells and then give it to animals such as mice or monkeys to see if it produces an immune response.
PHASE 1 SAFETY TRIALS: Scientists give the vaccine to a small number of people to test safety and dosage, as well as to confirm that it stimulates the immune system.
PHASE 2 EXPANDED TRIALS: Scientists give the vaccine to hundreds of people split into groups, such as children and the elderly, to see if the vaccine acts differently in them. These trials further test the vaccine’s safety.
PHASE 3 EFFICACY TRIALS: Scientists give the vaccine to thousands of people and wait to see how many become infected, compared with volunteers who received a placebo. These trials can determine if the vaccine protects against the coronavirus, measuring what’s known as the efficacy rate. Phase 3 trials are also large enough to reveal evidence of relatively rare side effects.
EARLY OR LIMITED APPROVAL: Many countries have procedures for providing emergency authorizations for vaccines, based on preliminary evidence that they are safe and effective. In addition, some countries such as China and Russia began administering vaccines before detailed Phase 3 trial data was made public. Experts have warned of serious risks from jumping ahead of these results.
APPROVAL: Regulators review the complete trial results and plans for a vaccine’s manufacturing, and decide whether to give it full approval.
COMBINED PHASES: One way to accelerate vaccine development is to combine phases. Some vaccines are now in Phase 1/2 trials, for example, which this tracker would count as both Phase 1 and Phase 2.
PAUSED or ABANDONED: If investigators observe worrying symptoms in volunteers, they can pause the trial. After an investigation, the trial may resume or be abandoned.
Genetic Vaccines
Vaccines that deliver one or more of the coronavirus’s own genes into our cells to provoke an immune response.
RNA vaccine
DNA vaccine
PHASE 2 PHASE 3 COMBINED PHASES
APPROVED IN SEVERAL COUNTRIES EMERGENCY USE IN U.S., ELSEWHERE
VACCINE NAME: Comirnaty (also known as tozinameran or BNT162b2)
EFFICACY: 91.3%
DOSE: 2 doses, 3 weeks apart
TYPE: Muscle injection
STORAGE: Freezer storage only at –13°F to 5°F (–25°C to –15°C)
On Nov. 9, New York-based Pfizer and the German company BioNTech made history by announcing that their coronavirus vaccine had an efficacy rate of over 90 percent, far surpassing expectations. It was the first time anyone had found such evidence. Just over a month later, on Dec. 11, the Food and Drug Administration granted it the first emergency use authorization ever given by the United States to a coronavirus vaccine. On May 10 the F.D.A. expanded the authorization to children as young as 12.
The work on the vaccine began in January 2020, when BioNTech researchers started fashioning a genetic molecule called messenger RNA (mRNA). They created the genetic instructions for building a coronavirus protein, known as spike. When injected into cells, the vaccine causes them to make spike proteins, which then get released into the body and provoke a response from the immune system. In March, BioNTech partnered with Pfizer to scale up the research, launching a clinical trial in May. They gave the vaccine the generic name tozinameran and the brand name Comirnaty
In Phase 1 trials, the researchers found that Comirnaty caused volunteers to produce antibodies against SARS-CoV-2, as well as immune cells called T cells that respond to the virus. On July 27, the companies announced the launch of a Phase 2/3 trial with 30,000 volunteers. On Sept. 12, Pfizer and BioNTech announced that they would seek to expand the trial to 44,000 participants.
Through the summer and into the fall, the world focused more and more of its attention on the Pfizer-BioNTech trial. In September, Dr. Albert Bourla, the chief executive of Pfizer, said that as soon as October the Phase 3 trial would deliver enough results to show if the vaccine worked or not. President Trump touted their progress, hinting that a vaccine would be available before the election. But on Oct. 27, Dr. Bourla announced that the volunteers in the trial had yet to experience enough cases of Covid-19 to determine if the vaccines work. Finally, on Nov. 9, Pfizer and BioNTech released their preliminary analysis of the first 94 cases.
Over the next month, Pfizer and BioNTech released more data on more cases. On Dec. 8 the FDA released their independent analysis of the clinical trials. They determined that Comirnaty has an efficacy rate of 95 percent. While Comirnaty caused no serious side effects, it frequently caused short-lived fatigue, fever, and muscle aches.
On Dec. 2, the United Kingdom gave emergency authorization to Pfizer and BioNTech’s vaccine, followed by many more countries. On Dec. 31, the World Health Organization gave the vaccine an Emergency Use Listing, which will speed up its authorization across the world. In Israel, which took the lead in mass vaccination, researchers found that the vaccine was as effective in the real world as the trials had indicated. A study published by the Centers for Disease Control in March found that the vaccine is 91.3% effective after the second dose. On May 7, Pfizer and BioNTech announced they would seek full F.D.A. approval for their vaccine. The process is expected to take several months.
As the trials progressed, Pfizer and BioNTech also scaled up factories to produce Comirnaty in huge amounts. To secure a supply in advance, the Trump administration awarded Pfizer and BioNTech a $1.9 billion contract in July 2020 for 100 million doses, but The New York Times reported in December that the administration passed up the chance over the summer to secure another 100 million doses. Since then, the Trump and Biden administrations reached agreements for a total of 300 million doses by the summer. In April 2021, the European Union negotiated a deal for 1.8 billion doses, which should close up the massive shortfall they experienced early in their vaccine rollout. In total, BioNTech and Pfizer expect to produce nearly 3 billion doses in 2021.
While Comirnaty has proven highly effective, it was initially a challenging vaccine to distribute because it had to be kept frozen at –94°F (–70°C). On Feb. 19, Pfizer and BioNTech announced that they could keep the vaccine stable at -25°C to -15°C (-13°F to 5°F).
In January, scientists grew concerned about the emergence of fast-spreading variants that might be able to evade antibodies. A study published in May demonstrated that Comirnaty was somewhat less effective against some variants, but still provided strong protection.
Comirnaty is currently being tested in a number of additional trials. In Feb. 2021, the companies announced a study to develop a B.1.351-specific booster. They are also running a trial specifically for pregnant women. The trial will determine whether the vaccine provides as much protection for them as for women who aren’t pregnant, and also gather information on its safety. Comirnaty is also one of several vaccines being tested in an Oxford study to gauge how well alternating doses promote immunity. Preliminary results from a different combination study suggests that a dose of the Astrazeneca vaccine followed by Comirnaty is safe and effective.
Dr. Bourla, the chief executive, said people would “likely” need an additional shot of its vaccine within a year of receiving two doses. He also said that it’s possible that vaccinations could recur each year.
For more details, see How the Pfizer-BioNTech Vaccine Works and How Pfizer Makes Its Covid-19 Vaccine.
APPROVED FOR USE IN: Bahrain, Brazil, New Zealand, Saudi Arabia, Switzerland.
EMERGENCY USE IN: Argentina, Australia, Botswana, Brunei, Canada, Chile, Colombia, Costa Rica, Ecuador, European Union, Greenland, Guatemala, Hong Kong, Iceland, Iraq, Israel, Japan, Jordan, Kuwait, Lebanon, Liechtenstein, Malaysia, Maldives, Mexico, Moldova, Monaco, Mongolia, Norway, North Macedonia, Oman, Panama, Peru, Philippines, Qatar, Serbia, Singapore, Sri Lanka NEW, South Africa, South Korea, Tunisia, Turkey, Ukraine, United Arab Emirates, United Kingdom, United States, Uruguay. Emergency use validation from the World Health Organization. Recommended for emergency use by the Caribbean Regulatory System.
Updated May 18
Pfizer-BioNTech
vaccine
BRITAIN AND
THE E.U.
MONGOLIA
CANADA
JAPAN
TUNISIA
IRAQ
U.S.
PHILIPPINES
BAHRAIN
SAUDI
ARABIA
MALAYSIA
MEXICO
BRAZIL
BOTSWANA
SINGAPORE
AUSTRALIA
PERU
NEW
ZEALAND
ARGENTINA
SOUTH
AFRICA
CHILE
Approved
Early, limited or
emergency use
PHASE 3
APPROVED IN SWITZERLAND EMERGENCY USE IN U.S., ELSEWHERE
VACCINE NAME: mRNA-1273
EFFICACY: More than 90%
DOSE: 2 doses, 4 weeks apart
TYPE: Muscle injection
STORAGE: 30 days with refrigeration, 6 months at –4°F (–20°C)
On Dec. 18., the F.D.A. gave emergency use authorization for a vaccine made by the Boston-based company Moderna. The Moderna vaccine is the second one authorized by the F.D.A., coming a week after the vaccine made by Pfizer and BioNTech.
Like Pfizer and BioNTech, Moderna makes its vaccine from mRNA. In recent years, the company has tested mRNA vaccines for a number of diseases, but they have yet to bring one to market. Last January, they began developing a vaccine for the coronavirus.
The United States government bankrolled Moderna’s efforts, providing nearly $1 billion in support. In partnership with National Institutes of Health, they found that the vaccine protects monkeys from the coronavirus. Last March, the scientists were the first to put a Covid-19 vaccine into human trials. After those studies yielded promising results, Phase 3 testing on 30,000 volunteers began on July 27.
On Nov. 16, Moderna announced the first preliminary data from the trial, followed by the complete data on Nov. 30. The researchers estimated that the vaccine had an efficacy rate of 94.1 percent. While it’s not clear how long this efficacy will last, Moderna has found that after three months the trial participants still have a strong immune defense against the coronavirus. On May 25, 2021, Moderna announced that the vaccine safely provided strong protection to children as young as 12. The company is currently testing the vaccine in babies and young children.
Meanwhile, the company entered deals with several countries to supply the vaccine pending its approval. On Aug. 11 last year, the United States government awarded the company an additional $1.5 billion in exchange for 100 million doses if the vaccine proves safe and effective. Additional negotiations have increased the agreement to 300 million doses by July 2021. On Nov. 25, the company reached an agreement with the European Commission to supply up to 160 million doses. Moderna has made similar deals with other countries including Canada, Japan, Qatar and South Korea. Moderna has also pledged 500 million doses to COVAX, a global vaccine initiative, to supply vaccines to low-income countries. On April 29, Moderna announced they would produce 800 million to 1 billion doses in 2021, and planned to manufacture 3 billion doses in 2022.
In March, Moderna began a Phase 1 trial of a vaccine made specifically for the B.1.351 variant. A variant-specific booster shot of the Moderna vaccine has yielded positive results in humans and mice. It is also conducting a Phase 1 trial of a new, refrigerator-stable vaccine. Moderna’s vaccine is one of several being tested in an Oxford study that gauges how well alternating doses can boost immunity.
For more details, see How Moderna’s Vaccine Works.
APPROVED FOR USE IN: Switzerland.
EMERGENCY USE IN: Canada, European Union, Greenland, Guatemala, Honduras, Iceland, Israel, Japan NEW, Kuwait, Moldova, Mongolia, Norway, Philippines, Qatar, Singapore, South Korea NEW, Taiwan, Thailand, United Kingdom, United States, Vietnam. Emergency use validation from the World Health Organization.
Updated May 21
Moderna vaccine
U.K. AND
E.U.
SWITZERLAND
CANADA
MONGOLIA
ISRAEL
U.S.
VIETNAM
QATAR
GUATEMALA
SINGAPORE
Approved
Early, limited or
emergency use
PHASE 3
VACCINE NAME: CVnCoV
EFFICACY: Unknown
DOSE: 2 doses, 4 weeks apart
TYPE: Muscle injection
STORAGE: Stable at least 3 months at 36–46°F (2–8°C)
Last March, the Trump administration unsuccessfully tried to entice CureVac to move its research on their mRNA vaccine from Germany to the United States. The company plowed ahead with its work in Germany, seeing responses to the vaccine in mice and monkeys before launching clinical trials in July. In December, CureVac launched a Phase 3 trial, recruiting up to 36,500 volunteers in Germany. The European Union began a rolling review in February, intended to speed up approval if the Phase 3 trial delivers positive results. CureVac expects the trial to show if the vaccine is safe and effective in May.
In November, CureVac negotiated a deal to provide the European Union with up to 400 million doses of their vaccine. They project manufacturing up to 300 million doses in 2021 and up to a billion doses the following year. CureVac has collaborated with Elon Musk’s company Tesla on creating mRNA “micro-factories,” which could potentially be deployed around the world to make billions of doses of the vaccine. On Nov. 12, the company announced that its vaccine could be kept in a refrigerator at 41 degrees. Other RNA vaccines made by Pfizer and Moderna have to be kept frozen at chillier temperatures.
Starting in January 2021, CureVac forged a series of partnerships with pharmaceutical giants Bayer, Celonic, GSK, and Novartis, to support the production of their vaccine and develop new ones against coronavirus variants.
Updated April 26
PHASE 3
VACCINE NAME: ZyCoV-D
EFFICACY: Unknown
DOSE: 3 doses, 4 weeks apart
TYPE: Skin injection
STORAGE: Stable at room temperature for three months
In July 2020, the Indian vaccine-maker Zydus Cadila began testing a DNA-based vaccine delivered by a skin patch. They launched a Phase 2 trial on ZyCoV-D on Aug. 6 and announced at the end of December that it was complete. On Jan. 3, 2021 the Indian government gave Zydus Cadila permission to advance to a Phase 3 trial with 30,000 volunteers. In an April 29 interview, the managing director of Zydus Cadila said that the trial could deliver efficacy results in May, after which the company will immediately seek emergency authorization from the Indian government.
Updated May 1
PHASE 2 PHASE 3 COMBINED PHASES
VACCINE NAME: AG0302-COVID19
EFFICACY: Unknown
DOSE: 2 doses, 2 weeks apart
TYPE: Skin injection
STORAGE: Over a year at room temperature
On June 30, the Japanese biotechnology company AnGes launched a Phase 1 trial to test a DNA-based vaccine, developed in partnership with Osaka University and Takara Bio. The company moved on to a Phase 2/3 trial in December.
Updated Dec. 8
PHASE 2
VACCINE NAME: INO-4800
EFFICACY: Unknown
DOSE: To be determined
TYPE: Skin injection
STORAGE: Over a year at room temperature
Before the pandemic, the Pennsylvania-based company Inovio developed DNA-based vaccines that are delivered into the skin with electric pulses from a hand-held device. They are running clinical trials for vaccines against a number of diseases, including HIV, Zika, and several forms of cancer. At the start of the pandemic, Inovio developed a DNA vaccine against the spike protein on the coronavirus. A Phase 1 trial, published in December, did not uncover any serious adverse effects, and measured an immune response in all 38 volunteers.
Inovio became embroiled in several lawsuits with stockholders and a company partner. On Sept. 28, the F.D.A. put the vaccine on a partial hold due to questions about the delivery device. On Nov. 16, Inovio said that the F.D.A. had given them permission to move forward.
Inovio went on to run Phase 2 trials in the United States as well as in China and South Korea, and posted results of the studies online on May 7, 2021. They also began testing versions of their vaccine tailored against new variants.
After losing government funding for Phase 3 trials, Inovio announced that it would proceed with testing its vaccine outside of the United States.
Updated May 10
PHASE 2
The California-based company Arcturus Therapeutics and Duke-NUS Medical School in Singapore have developed an mRNA vaccine. It has a “self-replicating” design that leads to a greater production of viral proteins. Tests on animals showed that it protected them against infection. In August, Arcturus launched a Phase 1/2 trial at Singapore General Hospital. On Nov. 9, the company announced that an interim analysis of the trial showed that the vaccine produced an immune response that’s in the range of responses seen in people who recovered from Covid-19. On Jan. 6 Arcturus announced that they had permission to start the Phase 2 portion of the trial in both Singapore and the United States. Singapore reached an agreement with Arcturus to spend up to $175 million to acquire vaccines when they’re ready.
Updated Jan. 12
PHASE 2
In June 2020, Chinese researchers at the Academy of Military Medical Sciences, Suzhou Abogen Biosciences and Walvax Biotechnology announced they would start their country’s first safety trials on an mRNA-based vaccine, called ARCoV. Earlier studies on monkeys reportedly showed protective effects, and in the Phase 1 trial indicated it was safe in people. On Dec. 21, Xinhua reported that China was building a factory to produce 120 million doses per year.
Researchers launched a Phase 2 trial for the vaccine in January 2021, and registered a Phase 3 trial in April. It was scheduled to begin the following month. The Global Times reported that the trial would likely be run in Latin America.
Updated April 20
PHASE 1 PHASE 2 COMBINED PHASES
Gennova Biopharmaceuticals in India and Seattle-based HDT Bio partnered to develop a vaccine based on self-amplifying RNA. The vaccine, known as HGC019, was able to safely provoke animals to make antibodies to the coronavirus, leading India to grant the companies approval in December 2020to start Phase 1/2 trials. On May 4, 2021 HDT announced the trial was underway in India.
Updated May 18
PHASE 1 PHASE 2 COMBINED PHASES
GeneOne Life Science, a South Korean biotech company, developed a DNA-based vaccine that encodes two proteins from the coronavirus. In December they launched a Phase 1/2 trial with 345 participants.
Updated Dec. 17
PHASE 1 PHASE 2 COMBINED PHASES
The South Korean company Genexine started testing the safety of a DNA-based vaccine in June 2020. In December, the Korea Biomedical Review reported that Genexine got disappointing results from their initial formulation and decided to restart their trials with a modified vaccine. On Jan. 20, the company registered a Phase 1/2 trial. The Indonesian pharmaceutical company Kalbe Farma pledged in April to buy 10 million doses of Genexine’s vaccine if it is proven to be safe and effective. Under the agreement, Kalbe Farma will pay for the Phase 2/3 clinical trial in Indonesia.
Updated May 1
PHASE 1 PHASE 2 COMBINED PHASES
Takis Biotech and Rottapharm Biotech, two vaccine companies in Italy, developed a vaccine called COVID-eVax. A special device uses a tiny electric pulse to deliver DNA through the skin. The DNA enters cells, which use the genetic instructions to make spike proteins. In February, Takis and Rottapharm launched a Phase 1/2 trial. COVID-eVax can remain stable at room temperature.
Updated March 15
PHASE 1 PHASE 2 COMBINED PHASES
The French pharmaceutical company Sanofi is developing an mRNA vaccine in partnership with Translate Bio. They have found that it produces a strong antibody response in mice and monkeys, and protects hamsters against coronavirus infections. In March the companies launched a Phase 1/2 trial, which they anticipate delivering results in the third quarter of 2021. The vaccine, known as MRT5500, is Sanofi’s second Covid-19 candidate in clinical trials, following their protein-based vaccine.
Updated April 20
PHASE 1 PHASE 2 COMBINED PHASES
Japan-based researchers at Daiichi Sankyo have developed an mRNA vaccine against the coronavirus in collaboration with the University of Tokyo. They launched a Phase 1/2 trial of the vaccine, named DS-5670, on March 22.
Updated March 23
PHASE 1 PHASE 2 COMBINED PHASES
Researchers at Baltimore-based Elixirgen Therapeutics have created an RNA vaccine, named EXG-5003, that targets a small part of the coronavirus spike protein. In May they launched a Phase 1/2 trial of the vaccine in Japan.
Updated May 25
PHASE 1
Researchers at Thailand’s Chulalongkorn University have been developing several potential vaccines for the coronavirus. The furthest along is an mRNA-based vaccine known as ChulaCov19. In September 2020, the Chula Vaccine Research Center registered a Phase 1 trial to test it in humans. Due to delays in funding and manufacturing, the trial is expected to begin in April or May 2021. In an interview with the Bangkok Post, the leader of the project said that up to 30 million doses might be produced for Thailand and six other Asian countries if the vaccine proved to be safe and effective.
Updated Feb. 23
PHASE 1
The Canadian company Entos Pharmaceuticals has created a DNA vaccine for the coronavirus. Most other genetic vaccines carry the gene for the spike protein on the surface of the virus. Entos instead chose the gene for nucleocapsid, a protein that sits inside the virus’s membrane. They are betting it can offer long-lasting immunity. In October 2020, Entos launched a Phase 1 trial in Canada for their vaccine, called Covigenix VAX-001. They began dosing participants on April 15.
Updated May 5
PHASE 1
On Nov. 2, the Canadian company Symvivo announced they had administered a DNA vaccine to their first volunteer in a Phase 1 trial. The DNA is inserted into harmless bacteria, which volunteers swallow in a frozen liquid (the company is working on putting the bacteria into a pill). When the bacteria reach the intestines, the DNA slips into cells in the gut lining, which then make viral proteins.
Updated Nov. 3
PHASE 1
New Jersey-based OncoSec Immunotherapies has developed experimental cancer treatments that deliver genes into tumors. There, the injected genes produce a natural signalling molecule called IL-12, which attracts the attention of immune cells that attack the cancer. In the spring, OncoSec began adapting their technology to make a vaccine for the coronavirus. The vaccine, called CORVax12, consists of a loop of DNA that encodes both the spike protein and IL-12. Causing the body to make extra IL-12 could potentially enhance the immune system’s ability to make antibodies to the spike protein. On Nov. 13, the company registered a Phase 1 trial to test the safety of the CORVax12.
Updated Nov. 13
PHASE 1
Canada’s Providence Therapeutics specializes in messenger RNA vaccines to treat cancer. In response to the pandemic, they developed an mRNA vaccine against the coronavirus. They launched a Phase 1 study of an RNA vaccine in late January. The company expects to move into Phase 2 trials by May.
Updated Jan. 28
PHASE 1
Using a delivery system from PharmaJet, researchers at BioNet-Asia and Australia-based Technovalia have developed a DNA vaccine called COVIGEN that can be pushed through the skin without a needle. Instead, the dose is loaded into a handheld device and shot directly into cell tissue through a jet spray of fluid. Vaccines for the flu already use the device, which PharmaJet says is a safer alternative to needle injections. The researchers registered a Phase 1 trial in Australia on Feb. 8.
Updated March 4
PHASE 1
Chinese researchers at Stemirna Therapeutics have developed an mRNA vaccine in collaboration with Shanghai East Hospital. They registered a Phase 1 trial on May 1.
Updated May 20
ABANDONED
In early 2020, Imperial College London researchers developed a “self-amplifying” RNA vaccine for Covid-19, which boosted production of a viral protein to stimulate the immune system. They began Phase 1/2 trials on June 15, partnering with Morningside Ventures to manufacture and distribute the vaccine through a new company called VacEquity Global Health. On Dec. 18, the researchers announced a collaboration with Enesi Pharma to formulate a solid version of the vaccine that can be implanted in the skin without a needle.
On Jan. 27, 2021, Robin Shattuck, the leader of the project, announced that “it is not the right time to start a new efficacy trial for a further vaccine in the U.K.” Instead of competing with authorized vaccines, they are turning their efforts to making candidates that will work well against emerging variants of the coronavirus.
Updated March 20
PRECLINICAL
Other genetic vaccines in active preclinical development include vaccines from: Applied DNA Sciences, EvviVax and Takis Biotech; CureVac and GSK; DIOSynVax; ETheRNA; EyeGene; Globe Biotech; Greenlight Biosciences; Infectious Disease Research Institute and Amyris; Mediphage Bioceuticals; National institute of Chemistry of Slovenia and Kemijski Inštitut; National Research Centre, Egypt; the OPENCORONA Consortia; Providence Therapeutics; Scancell; the Spanish National Center for Biotechnology and the Spanish National Research Council; Vaccibody.
Updated March 25
Viral Vector Vaccines
Vaccines that contain viruses engineered to carry coronavirus genes. Some viral vector vaccines enter cells and cause them to make viral proteins. Other viral vectors slowly replicate, carrying coronavirus proteins on their surface.
PHASE 3 EMERGENCY USE IN RUSSIA, ELSEWHERE
VACCINE NAME: Sputnik V (also known as Gam-Covid-Vac)
EFFICACY: 91.6%
DOSE: 2 doses, 3 weeks apart
TYPE: Muscle injection
STORAGE: Freezer storage. Developing an alternative formulation that can be refrigerated.
The Gamaleya Research Institute, part of Russia’s Ministry of Health, has created a vaccine with an efficacy rate of 91.6 percent. The creators of the vaccine published the results of their Phase 3 trial on Feb. 2 in the Lancet.
Gamaleya produced the vaccine, initially called Gam-Covid-Vac, from a combination of two adenoviruses called Ad5 and Ad26. Both kinds have been tested as vaccines over a number of years. By combining them, the Russian researchers hoped to avoid a situation in which the immune system could learn to recognize the vaccine as a foreign object that needed to be destroyed. The researchers launched clinical trials in June.
By the end of the summer, the trial became bogged down in controversy. On Aug. 11, President Vladimir V. Putin announced that a Russian health care regulator had approved the vaccine, renamed Sputnik V. Yet the Phase 3 trials had not even begun. Vaccine experts decried the move as risky, and Russia later walked back the announcement, saying that the approval was a “conditional registration certificate,” which would depend on positive results from Phase 3 trials. In addition to Russia, volunteers for the trial were recruited in Belarus, the United Arab Emirates, and Venezuela. On Oct. 17, a Phase 2/3 trial was launched in India.
On Sept. 4, three weeks after Putin’s announcement, Gamaleya researchers published the results of their Phase 1/2 trial. They found that Sputnik V yielded antibodies to the coronavirus and mild side effects. On Nov. 11, the Russian Direct Investment Fund announced the first preliminary evidence from their Phase 3 trial indicating that the vaccine is effective. Based on 20 cases of Covid-19 among the trial participants, Russian scientists estimated that the vaccine demonstrated 92 percent efficacy.
By December, the trial had reached its final total of 78 cases. The full details of the trial came out in February, demonstrating a high efficacy after two doses. The trial did not uncover serious side effects. No one who got the vaccine experienced a serious case of Covid-19.
The trial did not demonstrate how well Sputnik V can block new variants of the coronavirus. In a study posted online in April, researchers studied antibodies from people who had received the vaccine. They found that the Sputnik V antibodies often failed to neutralize the coronavirus, allowing it to infect cells.
In an unprecedented move in the coronavirus vaccine field, the Gamaleya Institute joined forces in December 2020 with the drugmaker AstraZeneca, which makes a vaccine based on a chimpanzee adenovirus. The two teams combined their vaccines to see if the mixture can increase the efficacy of the AstraZeneca vaccine. The trial began in February.
In November 2020, the Russian government began offering Sputnik V within Russia in a mass vaccination campaign. But worry that the vaccine was rushed to approval led to widespread hesitancy. On Dec. 22, Belarus became the first country outside of Russia to register Sputnik V, and since then a number of other countries have followed suit. In Europe, where the vaccine rollout faltered badly, regulators began a rolling review of Sputnik V on March 4. If the European Medicines Agency approved it, many European countries might take up the vaccine.
On April 26, the board of Brazil’s vaccine regulator rejected Sputnik V, saying that it contained adenoviruses that had not been properly disabled. Replicating adenoviruses could make the vaccine dangerous. Anvisa, Brazil’s regulatory agency, also complained of incomplete data about the vaccine’s efficacy and safety. The Russian developers pushed back against Anvisa’s claims and said they would sue for defamation. Brazil has also refused to conduct national clinical trials for Sputnik V.
In January 2021, Gamaleya researchers started a trial in which they gave people only the first dose of Ad26 adenoviruses, the same adenovirus in Johnson & Johnson’s single-dose vaccine. They dubbed this one-dose version “Sputnik Light.” On Feb. 12, the director of the Gameleya center said in a television interview that it would likely provide only four to five months of protection. Russia announced on May 6 that Sputnik Light provided an efficacy of 79.4 percent but did not publish the details of the study or say how long the efficacy would last. The Russian Ministry of Health said Sputnik Light provides sufficient protection on its own to be used without a second injection. Sputnik Light received authorization for use in Russia on May 6.
For more details, see How Gamaleya’s Vaccine Works.
EMERGENCY USE IN: Albania, Algeria, Angola, Antigua and Barbuda, Argentina, Armenia, Azerbaijan, Bahrain, Bangladesh, Belarus, Bolivia, Bosnian Serb Republic, Cameroon, Congo Republic, Djibouti, Ecuador NEW, Egypt, Honduras, Gabon, Ghana, Guatemala, Guinea, Guyana, Hungary, India, Iran, Iraq, Jordan, Kazakhstan, Kenya, Kyrgyzstan, Laos, Lebanon, Maldives NEW, Mali, Mauritius, Mexico, Moldova, Mongolia, Montenegro, Morocco, Myanmar, Namibia, Nepal, Nicaragua (including Sputnik Light), North Macedonia, Pakistan, Palestinian Authority, Panama, Paraguay, Philippines, Russia (including Sputnik Light), San Marino, Serbia, Seychelles, Slovakia, Sri Lanka, St. Vincent and the Grenadines, Syria, Tunisia, Turkey, Turkmenistan, United Arab Emirates, Uzbekistan, Venezuela (including Sputnik Light) NEW, Vietnam, Zimbabwe.
Updated May 25
Gamaleya’s
Sputnik V
vaccine
HUNGARY
RUSSIA
ALGERIA
MONGOLIA
GUINEA
PAKISTAN
IRAN
BAHRAIN
VIETNAM
GABON
MEXICO
INDIA
U.A.E.
VENEZUELA
ANGOLA
MYANMAR
BOLIVIA
KENYA
PARAGUAY
ARGENTINA
Approved
Early, limited or
emergency use
PHASE 2 PHASE 3 COMBINED PHASES
APPROVED IN BRAZIL EMERGENCY USE IN E.U., ELSEWHERE
VACCINE NAME: Vaxzevria (also known as AZD1222, or Covishield in India)
EFFICACY: 76% in a U.S. study.
DOSE: 2 doses
TYPE: Muscle injection
STORAGE: Stable in refrigerator for at least 6 months
A vaccine designed by the University of Oxford and produced by the British-Swedish company AstraZeneca has emerged as a key element in the effort to meet the global demand for Covid-19 vaccines. With an efficacy of 76 percent, the vaccine — now known as Vaxzevria — is being produced in vast quantities at a low price. Because it only needs to be refrigerated rather than frozen, it can be used far more widely than mRNA vaccines. But Vaxzevria’s journey has been turbulent, jolted by confusing messages from AstraZeneca, high-profile worries about safety, and difficulties with manufacturing.
In early 2020, Oxford researchers developed the vaccine by genetically engineering an adenovirus that normally infects chimpanzees. When they gave the vaccine to monkeys, they found that it protected the animals from the disease.
Teaming up with AstraZeneca, they followed up with a Phase 1/2 trial. The vaccine developers did not detect any severe side effects in the trial, while observing that the vaccine raised antibodies against the coronavirus as well as other immune defenses. AstraZeneca and Oxford then embarked on late-stage trials in the United Kingdom, South Africa, and elsewhere. But the researchers ran the trials independently, making it difficult to combine their results into a single clear picture of how well the vaccine worked. Making matters murkier, they gave different amounts of the vaccine to different people and also waited anywhere from four to twelve weeks to deliver the second dose.
On Dec. 8, AstraZeneca and Oxford published the first scientific paper on a Phase 3 clinical trial of a coronavirus vaccine. The trial demonstrated that the vaccine can protect people from Covid-19, but it left many questions unresolved about the results. Nevertheless, the vaccine’s low cost and ease of storage made it attractive to countries looking for a way out of the pandemic. The United Kingdom and Argentina were the first countries to give the vaccine emergency authorization, on Dec. 30. On Jan. 3, India approved a version called Covishield, made by the Serum Institute of India. On Feb. 16 the World Health Organization recommended the vaccine for emergency use in adults 18 or older. Brazil gave full approval to the vaccine on March 13. In the same month, Covax began delivering millions of doses of the vaccine to low- and middle-income countries. The company expects a total annual manufacturing capacity of two billion doses.
Yet even after millions of people began receiving the vaccine, new concerns arose. In South Africa, a small trial failed to demonstrate that it protected people against the variant B.1.351, which has become predominant in the country. On Feb. 7, South Africa halted plans for a rollout of 1 million doses of the AstraZeneca vaccine.
In March 2021, another concern emerged. European medical regulators became concerned about a small number of cases of blood clots in younger people who received Vaxzevria. The European Medicines Agency concluded that the vaccine had a very rare side effect in which people suffered blood clots in large veins combined with low platelets. The regulators emphasized that the vaccine is effective and the benefits it provided outweighed the small risk of its side effects. In response some countries chose to minimize the risk by restricting the vaccine to older people. In May, Norway permanently removed Vaxzevria from their vaccination program.
The United States has not yet authorized Vaxzevria, despite the lavish support it provided for its development. In 2020, the government gave AstraZeneca $1 billion to pay for research, clinical trials, and manufacturing. That summer, the company promised it would distribute Vaxzevria in the United States as soon as that October. But a concern about the health of a volunteer in the U.S. clinical trial stalled the study for seven weeks. AstraZeneca did not deliver the results of the trial until March 2021--only to be rebuked by its expert advisors for cherry-picking data. Two days later, the company announced that a fuller look at the trial showed that the vaccine had an efficacy of 76 percent against Covid-19, and 100 percent efficacy against severe disease and hospitalization. AstraZeneca is preparing its application to the F.D.A. for full authorization.
Even while it was running clinical trials, AstraZeneca reached agreements with a number of manufacturers in order to produce billions of doses of Vaxzevria. But in January 2021, it admitted that it would fall short of its promised delivery of vaccines to the European Union. Its shortfall grew only worse in March when India, facing an explosion of new cases, blocked export of the vaccine from its factories. On April 26, the European Commission announced it had filed a lawsuit against the company for breach of contract.
Yet India still struggled to vaccinate its own citizens while cases and deaths skyrocketed. The United States came under intense criticism for holding back raw materials India needed to make its own supply of Covishield. On April 25, the Biden administration announced it would partially lift its ban. But critics also point to a stockpile of millions of doses of AstraZeneca’s vaccine that the United States started building up last year. Now that the United States has enough vaccines from other companies to protect all its own citizens, there are calls to ship AstraZeneca’s vaccines to India and other countries in dire need. On April 25, Dr. Anthony Fauci said the United States government was considering sending the vaccines.
Meanwhile, AstraZeneca and Oxford are continuing research on the vaccine. On Feb. 14, they announced they would start trials on children as young as six. In an unprecedented move in the coronavirus vaccine field, they announced on Dec. 11 that they would collaborate with the Russian creators of the Sputnik V vaccine, which is also made from adenoviruses, to see if a combination with Sputnik V might increase the efficacy of the Oxford-AstraZeneca vaccine. The trial started in February 2021. Another combination trial is currently underway between the Oxford-AstraZeneca, Pfizer, Moderna and Novavax vaccines. Preliminary results from a different combination study suggests that a dose of Vaxzevria followed by the Pfizer and BioNTech vaccine is safe and effective. Oxford researchers have found that Vaxzevria works well as a third booster shot. AstraZeneca and Oxford are also working on a new version of the vaccine tailored to the B.1.351 variant and are testing a version that can be delivered as a nasal spray.
For more details, see How the Oxford-AstraZeneca Vaccine Works.
APPROVED FOR USE IN: Brazil.
STOPPED USE IN: Denmark, Norway.
EMERGENCY USE IN: Algeria, Angola NEW, Antigua, Argentina, Australia, Bahamas, Bahrain, Bangladesh, Barbados, Bhutan, Botswana, Brazil, Brunei, Cambodia, Canada, Chile, Colombia, Costa Rica, Cyprus NEW, Dominican Republic, Ecuador, Egypt, El Salvador, Ethiopia, European Union, Fiji, Georgia, Ghana, Greenland, Guatemala, Haiti NEW, Honduras, Hungary, Iceland, India, Indonesia, Iran, Iraq, Jamaica, Japan NEW, Kenya, Kuwait, Liechtenstein, Malaysia, Maldives, Mexico, Moldova, Mongolia, Morocco, Namibia, Nepal, Nigeria, North Macedonia, Norway, Pakistan, Papua New Guinea, Peru, Philippines, Rwanda NEW, Saudi Arabia, Seychelles, Sierra Leone, Sri Lanka, Solomon Islands, South Africa, South Korea, Sudan, Taiwan, Thailand, Uganda NEW, Ukraine, United Kingdom, Vietnam, Zambia. Emergency use validation from the World Health Organization. Endorsed by the Africa Regulatory Taskforce. Recommended for emergency use by the Caribbean Regulatory System.
Updated May 21
Oxford-
AstraZeneca
vaccine
NORWAY
BRITAIN AND
THE E.U.
CANADA
MOROCCO
MONGOLIA
SOUTH KOREA
ALGERIA
IRAN
BAHAMAS
PHILIPPINES
EGYPT
PAKISTAN
NIGERIA
MEXICO
INDIA
BRAZIL
KENYA
COSTA RICA
AUSTRALIA
NAMIBIA
MALDIVES
SEYCHELLES
CHILE
ARGENTINA
SOUTH
AFRICA
Approved
Stopped use
in favor of other
vaccines
Early, limited or
emergency use
PHASE 3
APPROVED IN CHINA EMERGENCY USE IN OTHER COUNTRIES
VACCINE NAME: Convidecia (also known as Ad5-nCoV)
EFFICACY: 65.28%
DOSE: Single dose
TYPE: Muscle injection
STORAGE: Refrigerated
The Chinese company CanSino Biologics developed Convidecia in partnership with the Institute of Biology at the country’s Academy of Military Medical Sciences. The one-shot vaccine is based on an adenovirus called Ad5. Last May, researchers published promising results from a Phase 1 safety trial on Convidecia, and in July they reported that their Phase 2 trials demonstrated the vaccine produced a strong immune response. In an unprecedented move, the Chinese military approved the vaccine on June 25 for a year as a “specially needed drug.” On Nov. 28, the Chief Executive of CanSino Biologics said in an interview that about 40,000 to 50,000 people had received Convidecia.
Starting in August 2020, CanSino began running Phase 3 trials in a number of countries, including Pakistan, Russia, Mexico and Chile. On Feb. 25, China announced the approval of the CanSino vaccine for general use. The company announced that its one-shot vaccine had an efficacy rate of 65.28 percent at preventing all symptomatic Covid-19 cases. The details of the trial have yet to be published. But on April 1, CanSino’s chief scientific officer said that the efficacy of its vaccine could drop over time. He also floated the idea of using a booster shot six months after the first dose, though more clinical trial data is needed.
On March 23, CanSino announced that it had won approval for a clinical trial of an inhaled version of the vaccine. Researchers have also begun to test whether giving alternating doses of vaccines from CanSino and Anhui Zhifei Longcom can boost their effectiveness.
APPROVED FOR USE IN: China.
EMERGENCY USE IN: Chile, Hungary, Mexico, Moldova NEW, Pakistan.
Updated May 18
CanSino vaccine
HUNGARY
CHINA
PAKISTAN
MEXICO
CHILE
Approved
Early, limited or
emergency use
PHASE 3 EMERGENCY USE IN U.S., ELSEWHERE
VACCINE NAME: Ad26.COV2.S
EFFICACY: 72% in United States, 68% in Brazil and 64% in South Africa
DOSE: 1 dose
TYPE: Muscle injection
STORAGE: Up to two years frozen at –4° F (–20° C), and up to three months refrigerated at 36–46° F (2–8° C).
On Feb. 27, the F.D.A. issued an emergency use authorization for Johnson & Johnson’s vaccine, making it the third coronavirus vaccine available in the United States. It was also the first to be shown to be safe and effective with just one dose rather than two.
The work that led to the vaccine started a decade ago at Beth Israel Deaconess Medical Center in Boston, where researchers developed a method for making vaccines out of a virus called Adenovirus 26, or Ad26 for short. Johnson & Johnson used Ad26 to develop vaccines for Ebola and other diseases with Ad26. Last January, the company and Beth Israel researchers collaborated on creating a coronavirus vaccine. In March they received $456 million from the United States government to support their move towards production. After the vaccine provided protection in experiments on monkeys, Johnson & Johnson began Phase 1/2 trials in July.
Based on promising results in these studies, Johnson & Johnson launched a Phase 3 trial in September using just one dose rather than two. Although Johnson & Johnson initially set out to recruit 60,000 volunteers, it capped the trial at 45,000 in December as cases rose.
On Jan. 29, Johnson & Johnson announced that the trial had proven that the vaccine was safe and effective, and the F.D.A. released a similar analysis on Feb. 24. Johnson & Johnson published a paper on the trial in the New England Journal of Medicine on April 21, 2021.
Bahrain became the first country to authorize the vaccine for emergency use on Feb. 25. Two days later, the United States followed suit. South Africa dropped plans to use AstraZeneca’s vaccine for their health care workers after a small trial failed to show it was effective against the B.1.351 variant that had grown dominant across the country. They began using Johnson & Johnson’s instead.
In August 2020, the federal government agreed to pay Johnson & Johnson $1 billion for 100 million doses if the vaccine was authorized. Most of the U.S. supply was supposed to be made by Baltimore-based Emergent Solutions. But the company struggled to get the vaccine’s complex manufacturing up and running. In April 2021, the F.D.A. issued a scathing report about the company’s lax standards. At least 15 million doses of Johnson & Johnson’s vaccine were contaminated at the factory. As a result, the company only delivered 4 million doses to the United States after authorization, shipping them from its factory in the Netherlands.
On April 13 the U.S. government recommended a pause in using the vaccine while it investigated reports of rare blood clots. Ten days later, C.D.C. researchers reported 15 cases of the unusual clots in nearly 8 million people who received the vaccine. The government decided to lift the pause and add a warning to the vaccine that younger women may run a slight risk of the severe side effect. At a May 12 meeting, C.D.C. researchers reported a total of 28 cases of blood clots in over 9 million vaccinations. Among women between the ages of 30-39, the rate is 12.4 cases per million doses. In women between 40 and 49, the rate is 9.4 cases per million doses. Among older women and men of all ages, there were fewer than 3 cases per million doses.
Johnson & Johnson’s contract calls for it to deliver 100 million doses by June 2021. As it works towards getting the Baltimore facility certified, it is also getting help from Merck, which announced on March 2 it would assist Johnson & Johnson with manufacturing the vaccine.
The European Union reached a similar deal on Oct. 8, 2020 for 200 million doses. But after concerns about rare blood clots emerged, reports surfaced that the E.U. might not renew its contract with the company. On March 29, a coalition of African countries announced that it has secured up to 400 million doses of the Johnson & Johnson vaccine through 2022. Shipments could begin as soon as the third quarter of 2021. COVAX, an international collaboration to deliver the vaccine equitably across the world, secured 500 million doses. The company is aiming for production of a billion doses in 2021.
On Nov. 16, 2020, Johnson & Johnson announced that they were also launching a second Phase 3 trial to observe the effects of two doses of their vaccine, instead of just one. The results are expected in the third quarter of 2021. In February, the company also launched a trial for pregnant women and in March it announced it would soon start trials on children. Johnson & Johnson’s chief executive said in a March 4 interview that the vaccine could become available for children by September.
For more details, see How the Johnson & Johnson Vaccine Works.
STOPPED USE IN: Denmark, Finland NEW.
EMERGENCY USE IN: Bahrain, Brazil, Canada, Colombia, European Union, Greenland, Iceland, Liechtenstein, Moldova NEW, Norway, Philippines, South Africa, South Korea, Switzerland, Thailand, United States, Zambia. Emergency use validation from the World Health Organization. Endorsed by the Africa Regulatory Taskforce.
Updated May 18
Johnson & Johnson
vaccine
EUROPEAN
UNION
FINLAND
CANADA
SOUTH
KOREA
U.S.
BAHRAIN
NIGERIA
THAILAND
BRAZIL
COLOMBIA
ZAMBIA
SOUTH
AFRICA
Approved
Stopped use
in favor of other
vaccines
Early, limited or
emergency use
PHASE 2 PHASE 3 COMBINED PHASES
The Italian biotechnology company ReiThera has developed a Covid-19 vaccine, called GRAd-COV2, that is based on an adenovirus that infects gorillas. Working in collaboration with the Lazzaro Spallanzani National Institute for Infectious Diseases in Rome, they found that it produced strong levels of antibodies in mice and monkeys. In July 2020, they launched a Phase 1 clinical trial. In November, they announced that the vaccine was well tolerated and produced antibodies, and released a report on the trial.
In March 2021, researchers launched a Phase 2 trial of the vaccine. But in May, Reuters reported, a court in Italy struck down the government’s plan to fund the Phase 3 trial, throwing the vaccine’s development into doubt. The government later said it was ready to fund the vaccine.
Updated May 25
PHASE 2
In the spring of 2020, the Israel Institute for Biological Research started work on a coronavirus vaccine based on vesicular stomatitis viruses. They engineered the viruses to carry the gene for the coronavirus spike protein. On Oct. 25, the Israeli government announced that the vaccine, called Brilife, would be going into a Phase 1 trial. The Phase 2 trial, which is recruiting up to 1,000 volunteers, started on Jan. 5. It’s not clear how the trial will fare now that Israel is aggressively vaccinating its citizens with authorized vaccines by Pfizer. The Jerusalem Post reported that because of trial delays, Brilife may not be ready for distribution until early 2023.
On March 15, the Jerusalem Post reported that Haddasah University Medical Center had signed an agreement to extend the trial to Brazil.
Updated May 6
PHASE 1
While many vaccines are given as injections, some vaccines can be taken as a pill. Oral vaccines have been approved for diseases including polio, cholera, and typhoid fever. The small San Francisco company Vaxart specializes in developing oral vaccines. They have created and tested pills for influenza and other diseases. Last spring Vaxart began work on an oral vaccine for Covid-19. It contains an adenovirus called Ad5 (the same viral vector in CanSinoBio’s vaccine and in Russia’s Sputnik V).
When Vaxart gave the pill to mice, they produced antibodies against the coronavirus. Mice don’t suffer symptoms of Covid-19, however, so the researchers then switched to hamsters, which do. In an unpublished study, they found that the vaccine pill not only dramatically reduced the amount of coronavirus in sick hamsters, but also protected them from two important symptoms of the disease: weight loss and swollen lungs.
The company’s stock price increased 3,600 percent in the first half of 2020. In June, The New York Times reported, a hedge fund that partly controlled the company sold off most of its shares, netting over $200 million in profits. In the wake of that reporting, the Department of Justice began investigating the company, while a number of shareholder lawsuits were brought against Vaxart, its executives and its board.
In October, the company began giving the pill to volunteers in a Phase 1 clinical trial. On Feb. 3, Vaxart announced that the trial revealed no serious safety concerns. While the pill produced a response from T cells, it didn’t produce encouraging neutralizing antibodies. Its stock price plunged 60 percent on the news. On Feb. 25, the company announced it would advance to a Phase 2 trial in the second quarter of 2021.
Updated March 20
PHASE 1
In 2019, researchers at the University of Hong Kong and Xiamen University created a nasal-spray vaccine for the flu based on a genetically weakened form of the influenza virus. In early 2020, they engineered the vaccine to produce part of the coronavirus spike protein as well. On Sept. 9, they received approval to start clinical trials in partnership with Beijing Wantai Biological Pharmacy. They registered a Phase 1 trial on March 22, 2021. The researchers are receiving $5.4 million in support from CEPI, the Coalition for Epidemic Preparedness Innovations.
Updated March 22
PHASE 1
Three decades ago, the German Center for Infection Research developed a smallpox vaccine from a harmless virus called Modified Vaccinia Ankara, or MVA for short. In recent years, they adapted it to create a vaccine for MERS, a disease caused by another coronavirus.
This spring, they made an MVA-based vaccine for SARS-CoV-2, the coronavirus that is causing the Covid-19 pandemic. It carries the gene for the spike protein, which is produced inside cells that it invades. On Sept. 29, the center and a consortium of German universities registered a Phase 1 trial. In January the center announced that their initial formulation provided disappointing results and are postponing the trial until they update it.
Updated Jan. 13
PHASE 1
The California-based company ImmunityBio created a vaccine using the Ad5 adenovirus, the same one used by CanSinoBio and the Gamaleya Institute in Russia. ImmunityBio engineered the Ad5 virus to carry genes for two genes from the coronavirus. In addition to the spike protein, it also carries the gene for a protein called nucleocapsid. The company hopes that this combination will provoke a strong immune response.
The company found that the vaccine protects monkeys from the coronavirus. ImmunityBio launched a Phase 1 trial of a Covid-19 vaccine in October in the United States and another in South Africa in January. In February the company registered a Phase 1 trial of an oral version of the vaccine.
On May 25, the company announced that it would study how well their candidate works as a booster shot for those who already received other vaccines. They are also testing a nasal spray version.
The chairman and C.E.O. of ImmunityBio is billionaire Patrick Soon-Shiong, the owner of the Los Angeles Times.
Updated May 25
PHASE 1
Researchers at City of Hope, a California biomedical research institute, created a vaccine based on a weakened form of a virus called Modified Vaccinia Ankara, or MVA for short. They added two coronavirus genes to the virus — one for the spike protein, and one for another protein called nucleocapsid. They hope the combination will enable the vaccine to produce immunity that’s both fast and long-lasting. On Nov. 24 they announced the start of a Phase 1 trial, with hopes for a Phase 2 trial to start in the second quarter of 2021. But the researchers have faced delays in recruiting enough participants for their Phase 1 study. As of March 12, they had reached less than half of their goal of 129 participants.
Updated March 31
PHASE 1
In April, the South Korean biotech company Cellid began to develop a vaccine for Covid-19. The vaccine is based on a combination of two strains of adenoviruses, called Ad5 and Ad35. After testing the vaccine on monkeys, Cellid entered into a partnership with the South Korean chemical manufacturer LG Chem to manufacture the vaccine. In December, they registered a Phase 1 trial.
Updated Dec. 14
PHASE 1
VACCINE NAME: AdCOVID
EFFICACY: Unknown
DOSE: 1 dose
TYPE: Nasal spray
STORAGE: Refrigerated
Maryland-based Altimmune is a biopharmaceutical company that focuses on developing vaccines delivered by nasal spray. Recently, they’ve tackled influenza and anthrax using this technology. They have now used it to make a nasal spray vaccine for Covid-19, delivering the Ad5 adenovirus to the airway. The company says its nasal spray may be more effective for blocking the transmission of the virus than vaccines given by injection. In a study on mice, AltImmune researchers found that a single dose of the vaccine gave complete protection from a lethal infection of coronaviruses. On Dec. 22, the company registered a Phase 1 clinical trial of a single dose of the vaccine, which is expected to deliver results in June 2021.
Updated May 25
PHASE 1
On Feb. 11, Indian regulators gave Bharat Biotech approval to launch a Phase 1 trial of a vaccine delivered as a nasal spray. The spray, called BBV154, contains a chimpanzee adenovirus developed by researchers at Washington University. They found that it could produce coronavirus antibodies in mice with just a single dose. BBV154 is Bharat Biotech’s second foray into coronavirus vaccine clinical trials. Their vaccine Covaxin, made of inactivated coronaviruses, is already in emergency use in India.
Updated Feb. 16
PHASE 1
In 2020, researchers at the Icahn School of Medicine at Mount Sinai in New York developed a Covid-19 vaccine based on a virus called Newcastle Disease Virus, or NDV for short. NDV is a bird pathogen and does not cause symptoms in humans. The researchers engineered NDV to carry the gene for a modified version of the coronavirus spike protein called HexaPro, developed at the University of Texas. They then grew the modified virus in chicken eggs. The researchers inactivated the NDVs with chemicals and combined them with immune-boosting chemicals called adjuvants. The researchers found that the vaccine produced high levels of coronavirus antibodies in mice and hamsters. They published the results of their experiments in November.
On Feb. 22, Mahidol University in Thailand registered a Phase 1 trial of the vaccine, called NDV-HXP-S. They are running the trial in collaboration with the Government Pharmaceutical Organization, a Thai state-run drug manufacturer. Avi-Mex in Mexico also licensed NDV-HXP-S and launched its own Phase 1 trial. The Institute of Vaccines and Medical Biologicals in Vietnam has done the same. In Brazil, the Butantan Institute has applied for permission to start a trial as well, which is expected to start soon.
The vaccine could potentially help low- to middle-income countries secure their own supplies of Covid-19 vaccines. The virus can be safely grown in large quantities in chicken eggs, the same way influenza vaccines have been produced since the 1950s. As a result, NDV-HXP-S could be very cheap to make.
Updated May 6
PHASE 1
Gritstone Oncology has developed experimental vaccines in recent years that teach the immune system to attack tumors. Last year they constructed a vaccine for Covid-19 that presents a number of targets in the coronavirus for attack.
The researchers constructed a piece of DNA that encodes the entire spike protein of the coronavirus. In addition, it encodes instructions for building small pieces of other viral proteins called nucleocapsid and ORF3a. They then inserted this cassette into the genes of a chimpanzee adenovirus. The spike protein provokes the body to make antibodies, while the pieces of other proteins train the immune system to recognize infected cells and kill them.
In addition, the researchers created an RNA molecule with the same genetic instructions, which they put in a shell. Once the shell slips into a cell, the RNA molecule can make copies of itself, and the cell then makes proteins from those copies.
In a Phase 1 trial launched in March, the National Institute of Allergy and Infectious Diseases is testing how well these two vaccines work together, with the chimpanzee adenovirus serving as the first dose and the self-amplifying RNA as the second. The researchers hope that this combination will produce a better immune response than two doses of either vaccine.
Updated March 4
PHASE 1
Meissa Vaccines has developed a vaccine that can be delivered as a spray or drops into the nose. To make the vaccine, researchers started off with another virus, called respiratory syncytial virus (RSV for short). The researchers introduced mutations into the RSV virus’s genes so that it replicated too slowly to cause disease. Then they added a gene for the coronavirus spike protein, so that the weakened RSV viruses could present it to the immune system. On March 15, Meissa registered a Phase 1 trial for the vaccine.
Updated March 20
ABANDONED
The American company Merck acquired the Austrian firm Themis Bioscience in June to develop their vaccine, which had been originally developed at Institut Pasteur. The vaccine used a weakened measles virus that carries a gene for the coronavirus spike protein. Researchers launched a Phase 1 trial in August. On Jan. 25, Merck announced it was abandoning the effort, because the vaccine provoked a response that was weaker than a natural infection. In March they entered into a partnership with Johnson & Johnson to help produce their vaccine instead.
Updated March 4
ABANDONED
In addition to its project with Themis, Merck partnered with IAVI on a second viral vector vaccine. It was based on vesicular stomatitis viruses, the same approach Merck successfully used to produce the first approved vaccine for Ebola. They designed their coronavirus vaccine as a pill, which could have made it easier to distribute than syringes for injections. Merck and IAVI received $38 million from the United States government to support their research, and on September 30 they registered a Phase 1 trial. But on Jan. 25, they announced they were abandoning the effort because the vaccine failed to trigger an immune system comparable to what happens in a natural infection of Covid-19.
Updated Jan. 25
PRECLINICAL
Other viral vector vaccines in active preclinical development include vaccines from: Ankara University; ID Pharma; Institut Pasteur Lille; KU Leuven; Ohio State University and Kazakh National Agrarian University; the Spanish National Center for Biotechnology and the Spanish National Research Council; TheraVectys and Institut Pasteur; Thomas Jefferson University and Bharat Biotech; Tonix Pharmaceuticals; University of Georgia; University of Helsinki, University of Eastern Finland, and Rokote Laboratories Finland; University of Pittsburgh; University of Western Ontario; Valo Therapeutics and University of Helsinki; Vivaldi Biosciences; Walvax Biotechnology, Tsinghua University, and Tianjin Medical University; Zydus Cadila.
Updated Feb. 18
Protein-Based Vaccines
Vaccines that contain coronavirus proteins but no genetic material. Some vaccines contain whole proteins, and some contain fragments of them. Some pack many of these molecules on nanoparticles.
PHASE 3
APPROVED IN TURKMENISTAN EARLY USE IN RUSSIA
VACCINE NAME: EpiVacCorona
EFFICACY: Unknown
DOSE: 2 doses, 3 weeks apart
TYPE: Muscle injection
STORAGE: Stable in refrigerator for up to two years
On Aug. 26, the Vector Institute, a Russian biological research center, registered a Phase 1/2 trial for a coronavirus vaccine they call EpiVacCorona. The vaccine contains small portions of viral proteins, known as peptides. Less than two months later, on Oct. 14, Vladimir Putin announced that Russia has granted regulatory approval to the vaccine, making it the second one to receive that designation after the Gamaleya Institute’s Sputnik V vaccine.
A Phase 3 trial began in November, and as of Dec. 15, the Interfax News Agency reported that 1,438 volunteers had received the vaccine.
In January, Russia launched a mass vaccination campaign that included EpiVacCorona.. In February, Tass reported that the immune response from EpiVacCorona lasted “for approximately a year.” On March 3, the Vector Institute registered their trial on an international registry, indicating that they expected to deliver preliminary results in August 2021. Tass reported in early May that more than 90% of people who received the vaccine developed antibodies.
Results from EpiVacCorona’s Phase 1/2 trial were published in an obscure Russian journal in late March, but the data has concerned outside experts, who have pointed out serious flaws in the study.
APPROVED FOR USE IN: Turkmenistan.
EARLY USE IN: Russia.
Updated May 6
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