Vaccine, Where we are, What's next?

Researchers are testing 44 vaccines in clinical trials on humans, and at least 91 preclinical vaccines are under active investigation in animals.

Vaccines typically require years of research and testing before reaching the clinic, but scientists are racing to produce a safe and effective coronavirus vaccine by next year. Work began in January with the deciphering of the SARS-CoV-2 genome. The first vaccine safety trials in humans started in March, but the road ahead remains uncertain. Some trials will fail, and others may end without a clear result. But a few may succeed in stimula-ting the immune system to produce effective anti bodies against the virus. Here is their progress.

HOW ARE VACCINES TESTED?

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. We have confirmed 91 preclinical vaccines in active development.

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 and ability to stimulate the immune system.

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. In addition, Phase 3 trials are large enough to reveal evidence of relatively rare side effects that might be missed in earlier studies.

EARLY OR LIMITED APPROVAL

China and Russia have approved vaccines without waiting for the results of Phase 3 trials. Experts say the rushed process has serious risks.

APPROVAL

Regulators in each country review the trial results and decide whether to approve the vaccine or not. During a pandemic, a vaccine may receive emergency use authorisation before getting formal approval. Once a vaccine is licensed, researchers continue to monitor people who receive it to make sure it’s safe and effective.

COMBINED PHASES

One way to accelerate vaccine development is to combine phases. Some coronavirus vaccines are now in Phase 1/2 trials, for example, in which they are tested for the first time on hundreds of people.

Types of Vaccines
Types of Vaccines

PHASE 1

Inovio •••

The American company Inovio has developed DNA- based vaccines which are delivered into the skin with electric pulses from a hand-held device. They have vaccines in clinical trials for a number of diseases, and in June they announced interim data from a Phase 1 trial on COVID-19. They found no serious adverse effects, and measured an immune response in 34 out of 36 volunteers.

Genexine •••

The Korean company Genexine started testing the safety of a DNA-based vaccine in June. They anticipate moving to Phase 2 trials in the fall.

ARCoV •••

In June, 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 a mRNA-based vaccine, called ARCoV. Earlier studies on monkeys reportedly showed protective effects.

ChulaCov19 •••

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. On Sept. 29, the Chula Vaccine Research Center registered a Phase 1 trial to test it in humans.

GRAd-COV2 •••

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 launched a Phase 1 trial at the end of July.

Vaxart •••

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. Earlier this year, the small San Francisco- based company 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). In September, Vaxart reported that mice given the pill produced antibodies against the coronavirus. On September 24, they registered a Phase 1 clinical trial.

Merck + Themis •••

The American company Merck acquired the Austrian firm Themis Bioscience in June and is working on a vaccine originally developed at Institut Pasteur. The vaccine uses a weakened measles virus that carries a gene for the coronavirus spike protein. Researchers launched a Phase I trial in August.

University of Hong Kong + Xiamen University •••

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. Earlier this year, they engineered the vaccine to produce part of the coronavirus spike protein as well. On September 9, they received approval to start clinical trials in partnership with Beijing Wantai Biological Pharmacy.

German Center for Infection Research •••

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 modified it to create a vaccine for MERS, a disease caused by another coronavirus. This spring, they made an MVA-based vaccine for 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 September 29, the center and a consortium of German universities registered a Phase 1 trial.

Merck + IAVI •••

In addition to its project with Themis, Merck is part- nering with IAVI on a second viral vector vaccine. It is based on vesicular stomatitis viruses, the same approach Merck successfully used to produce the first approved vaccine for Ebola. They have designed their coronavirus vaccine as a pill, which could potentially make 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.

Clover Biopharmaceuticals •••

Clover Biopharmaceuticals has developed a vaccine containing the spike protein from coronaviruses. To further stimulate the immune system, the vaccine is being given in conjunction with so-called adjuvants made by British drugmaker GSK and the American company Dynavax. Investments from CEPI will support the development of manufacturing that could lead to the production of hundreds of millions of doses a year. Clover launched a Phase 1 trial in June. In September the company announced that it was expanding the trial and anticipated starting a Phase 2 trial by the end of 2020.

University of Queensland •••

A vaccine from Australia’s University of Queensland delivers viral proteins altered to draw a stronger immune response. Experiments on hamsters showed that the vaccine protected them from the coronavirus. The uni- versity launched Phase 1 trials in July, combining the proteins with an adjuvant made by CSL. If the results are positive, CSL will advance late stage clinical trials by the end of 2020.

Medicago •••

Canada-based Medicago, partly funded by the cigarette maker Philip Morris, uses a species of tobacco to make vaccines. They deliver virus genes into leaves, and the plant cells then create protein shells that mimic viruses. In July, Medicago launched Phase 1 trials on a plant-based COVID-19 vaccine in combination with adjuvants from drug makers GSK and Dynavax. If the trial goes well, they plan to start Phase 2/3 trials in October.

Vaxine •••

The Australian company Vaxine developed a vaccine that combines viral proteins with an adjuvant that stimulates the immune system. Phase 1 trials began over the summer, and Phase 2 trials are expected to commence by the end of the year.

Kentucky BioProcessing •••

A second tobacco-based vaccine is in development at Kentucky Bio Processing, an American subsidiary of British American Tobacco, the maker of Lucky Strike and other cigarettes. Like Medicago, Kentucky Bio Pro- cessing engineers a species of tobacco called Nicotiana benthamianato make viral proteins. The company previously used this technique to make a drug called Zmapp for Ebola. After preclinical testing in the spring, they registered a Phase 1 trial for their coronavirus vaccine in July.

Medigen •••

Taiwan-based vaccine maker Medigen is making a vaccine made of a combination of spike proteins and an adjuvant from Dynavax. They have registered a Phase 1 trial set to start in September.

Adimmune •••

Taiwan-based vaccine manufacturer Adimmune got permission to launch a Phase 1 trial on August 20. The vaccine contains the RBD section of the virus’s spike protein.

West China Hospital of Sichuan University •••

In July, researchers at West China Hospital of Sichuan University published a study in Nature describing a vaccine made from the RBD region of the spike protein that could protect mice and monkeys from the corona- virus. On August 24, they got approval to run a Phase 1 trial. To make the vaccine, researchers encode the RBD region in a gene, which they insert into a virus. They then infect insect cells with the virus, causing them to make the molecule in huge amounts.

COVAXX •••

New York-based COVAXX, a subsidiary of United Biomedical, has created a vaccine containing parts of several viral proteins. On Sept. 11 they registered a Phase 1 trial in Taiwan. They have reached an agreement with authorities in Brazil to run their Phase 2/3 trial there.

University of Tübingen •••

In the spring, researchers at the University of Tübingen in Germany created a vaccine made of eight parts of two viral proteins, along with an immune- stimulating adjuvant. In September they launched a Phase 1 trial.

North Korea’s State Commission •••

On July 18, North Korea’s State Commission of Science and Technology announced on their web site that they had started clinical trials on a vaccine based on part of the coronavirus spike protein. The commission claimed to have tested the vaccine on animals, but provided no data. It stated that effectiveness trials would have to be carried out in another country “since there is no case of Covid-19 in DPR Korea.” Outside experts find this claim highly doubtful.

QazCovid •••

The Central Asian nation of The Republic of Kazakhstan began research on a vaccine made from inactivated coronaviruses over the summer. On August 28, their Research Institute for Biological Safety Problems regis- tered a Phase 1 trial on the vaccine, known as QazCovid.

PHASE 1- PHASE 2 Combined Phase

Imperial College London •••

Imperial College London researchers have developed a “self-amplifying” RNA vaccine, which boosts production of a viral protein to stimulate the immune system. They began Phase 1/2 trials on June 15 and have partnered with Morningside Ventures to manufacture and distribute the vaccine through a new company called VacEquity Global Health.

AnGes + Osaka University •••

On June 30, the Japanese biotechnology company AnGes announced they had started Phase 1 trials on a DNA-based vaccine, developed in partnership with Osaka University and Takara Bio. The company will announce initial results of the trials in November and are planning for a Phase 3 trial by the end of the year.

Arcturus + Duke-NUS Singapore •••

The California-based company Arcturus Therapeutics and Duke-NUS Medical School in Singapore have devel- oped 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.

Soberana 1 •••

On August 18, the head of epidemiology at Cuba’s public health ministry announced that the Finlay Vaccine Institute in Havana would start a clinical trial on a vaccine for COVID-19. The vaccine, called Soberana 1, contains a part of the spike protein, called RBD, along with an adjuvant to boost the immune response.

EpiVacCorona •••

On August 26, a Russian biological research centre, The Vector Institute, registered a Phase 1/2 trial for a coronavi- rus vaccine they call EpiVacCorona. The vaccine contains small portions of viral proteins, known as peptides. Ac- cording to newspaper reports, the EpiVacCorona trials had already begun by then, with plans for distribution of the vaccine by the end of the year.

Sanofi •••

In addition to their mRNA vaccine, Sanofi developed a COVID-19 vaccine based on viral proteins. They pro- duced the proteins with engineered viruses that grow inside insect cells. GSK supplemented these proteins with adjuvants that stimulate the immune system. The vaccine is based on the same design Sanofi used to create Flublok, an approved vaccine for influenza. The companies launched a Phase 1/2 clinical trial in September. They plan to start a Phase 3 trial in December and hope to know if the vaccine is safe and effective by the middle of 2021.

SpyBiotech •••

SpyBiotech, a company spun off from the University of Oxford, announced in September that the first volunteers in an Australian Phase 1/2 trial were receiving their COVID-19 vaccine. The researchers created the vaccine from a mixture of proteins. Some of the proteins, from hepatitis B viruses, assemble themselves into hollow shells. The researchers decorated these shells with part of the coronavirus spike protein. The Serum Institute of India, which licensed the technology from SpyBiotech, is running the trials.

PHASE 2

Zydus Cadila •••

In July, the Indian vaccine-maker Zydus Cadila began testing a DNA-based vaccine delivered by a skin patch. They launched a Phase 2 trial on Aug. 6.

CureVac •••

CureVac launched its clinical trials of an mRNA vaccine, gave injections in September to volunteers and Panama and Peru for a Phase 2 study, and planned for a Phase 3 trial by the end of 2020. In an interview, the chief executive of CureVac said that the company would make 100 million doses by the end of 2020 and hoped to gain approval some time in 2021. 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.

Anhui Zhifei Longcom •••

In July, the Chinese company Anhui Zhifei Longcom began Phase 2 trials for a vaccine that is a combination of viral proteins and an adjuvant that stimulates the immune system. The company is part of Chongqing Zhifei Biological Products and has partnered with the Chinese Academy of Medical Sciences.

Chinese Academy of Medical Sciences •••

Researchers at the Institute of Medical Biology at the Chinese Academy of Medical Sciences, which has invented vaccines for polio and hepatitis A, started a Phase 2 trial of an inactivated virus vaccine in June.

ICMR + Bharat Biotech •••

In collaboration with the Indian Council of Medical Research and the National Institute of Virology, the Indian company Bharat Biotech designed a vaccine called Covaxin based on an inactivated form of the coronavirus. Studies on monkeys and hamsters found that it provided protection against infection. When the company launched clinical trials in July, reports circulated that the vaccine would be ready by August 15. But the C.E.O. of Bharat told reporters it would be available no sooner than early 2021.

PHASE 2- PHASE 3 Combined Phase

BioNTech + Pfizer + Fosun Pharma •••

The German company BioNTech entered into col- laborations with Pfizer, based in New York, and the Chinese drug maker Fosun Pharma to develop an mRNA vaccine to be given in two doses. In May they launched a Phase 1/2 trial on two versions of the vaccine. They found that both versions caused volunteers to produce antibodies against SARS-CoV-2, as well as immune cells called T cells that respond to the virus. They found that one version, called BNT162b2, produced significantly fewer side effects, such as fevers and fatigue, and so they chose it to move into Phase 2/3 trials. On July 27, the companies announced the launch of a Phase 2/3 trial with 30,000 volunteers in the United States and other countries including Argentina, Brazil, and Germany.

In September, the chief executive of Pfizer said they would know if the vaccine works as soon as October 2020. If approved, Pfizer has said they expect to manu- facture over 1.3 billion doses of their vaccine worldwide by the end of 2021.

AstraZeneca + University of Oxford •••

A vaccine in development by the British-Swedish company AstraZeneca and the University of Oxford is based on a chimpanzee adenovirus called ChAdOx1. A study on monkeys found that the vaccine provided them protection. In May, the United States awarded the project $1.2 billion in support. In their Phase 1/2 trial, the vaccine developers did not detect any severe side effects. They found that the vaccine raised antibodies against the coronavirus as well as other immune defenses. The vaccine began Phase 2/3 trials in England and India, as well as Phase 3 trials in Brazil, South Africa, and the United States.

In August the European Union reached an agree- ment for AstraZeneca to deliver 400 million doses if the trials yield positive results. AstraZeneca has indicated they might be able to start delivering emer- gency vaccines as early as October, depending on the outcome of the studies. The company has said their total manufacturing capacity for the vaccine, if approved, stands at two billion doses. India’s Serum Institute has already produced millions of doses to be used in trials.

On Sept. 6, AstraZeneca halted global trials of the vaccine to investigate one volunteer, who developed a form of inflammation called transverse myelitis. Within a week, the trials began resuming. As of now, however, the United States is still keeping its trial on pause as the F.D.A. investigates.

PHASE 3

National Institutes of Health + Moderna •••

Moderna develops vaccines based on messenger RNA (mRNA) to produce viral proteins in the body. They have yet to bring one to the market. In January, they began developing a vaccine for the coronavirus and since then the government has bankrolled Moderna’s efforts, pro- viding nearly $1 billion. In partnership with National Institutes of Health, they found that the vaccine protects monkeys from the coronavirus. In March, the company put the first COVID-19 vaccine into human trials, which yielded promising results. The vaccine has progressed into Phase 3 testing, which began on July 27. The final trial is enrolling 30,000 healthy people at about 89 sites around the United States. On August 11, the government awarded the company an additional $1.5 billion in exchange for 100 million doses if the vaccine proves safe and effective. Canada agreed in September to acquire 20 million doses. In July, Moderna lost a patent dispute over some of their vaccine technology. The following month, the company stated that it could not be certain it was the first to make the inventions claimed in their patents, including its coronavirus vaccine.

On Sept. 17, Moderna shared their protocol for determining if their vaccine was safe and effective. They planned to wait until a significant number of volunteers became sick with COVID-19 and then see how many had been vaccinated. It may take till the end of 2020 or early 2021 to reach the necessary numbers.

Johnson & Johnson •••

A decade ago, researchers at Beth Israel Deaconess Medical Center in Boston developed a method for making vaccines out of a virus called Adenovirus 26, or Ad26 for short. Johnson & Johnson developed vaccines for Ebola and other diseases with Ad26 and have now made one for the coronavirus. In March they received $456 million from the United States government to support their move towards production. The vaccine has provided protection in experiments on monkeys. Johnson & Johnson began Phase 1/2 trials in July and launched a Phase 3 trial with up to 60,000 participants in September.

In August, the federal government agreed to pay $1 billion for 100 million doses if the vaccine is approved. The company is aiming for production of at least a billion doses in 2021.

Novavax •••

Maryland-based Novavax makes vaccines by sticking proteins onto microscopic particles. They’ve taken on a number of different diseases this way; their flu vaccine finished Phase 3 trials in March. The company launched trials for a COVID-19 vaccine in May, and the Coalition for Epidemic Preparedness Innovations has invested $384 million in the vaccine. In July the U.S. government awarded $1.6 billion to support the vaccine’s clinical trials and manufacturing. After getting promising results from preliminary studies in monkeys and humans, Novavax launched a Phase 2 trial in South Africa in August. The blinded, placebo-controlled trial on 2,900 people will measure not just the safety of the vaccine but its efficacy. The following month, Novavax launched a Phase 3 trial enrolling up to 10,000 volunteers in the United Kingdom. It could potentially deliver results by the start of 2021. A larger Phase 3 trial is in development to launch in the United States in October.

If the trials succeed, Novavax expects to deliver 100 million doses for use in the United States by the first quarter of 2021. In September Novavax reached an agreement with the Serum Institute of India, a major vaccine manufacturer, that they said would enable them to produce as many as 2 billion doses a year.

BCG Vaccine •••

The Bacillus Calmette-Guerin vaccine was developed in the early 1900s as a protection against tuberculosis. The Murdoch Children’s Research Institute in Australia is conducting a Phase 3 trial called the BRACE to see if the vaccine partly protects against the coronavirus.

PHASE 3 APPROVED FOR LIMITED USE

CanSino Biologics •••

The Chinese company CanSino Biologics developed a vaccine based on an adenovirus called Ad5, in partnership with the Institute of Biology at the country’s Academy of Military Medical Sciences. In May, they published promising results from a Phase 1 safety trial, 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.” CanSino would not say whether vaccination would be mandatory or optional for soldiers. Starting in August, CanSino began running Phase 3 trials in a number of countries, including Saudi Arabia, Pakistan and Russia.

Sputnik V, •••

The Gamaleya Research Institute, part of Russia’s Ministry of Health, launched clinical trials in June of a vaccine they called Gam-Covid-Vac. It is a combination of two adenoviruses, Ad5 and Ad26, both engineered with a coronavirus gene.

On Aug. 11, President Vladimir V. Putin announced that a Russian health care regulator had approved the vaccine, renamed Sputnik V, before Phase 3 trials had 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. Those trials, initially planned for just 2,000 volunteers, were expanded to 40,000. On September 4, three weeks after Putin’s announcement, Gamaleya researchers published the results of their Phase 1/2 trial. In a small study, they found that Sputnik yielded antibodies to the coronavirus and mild side effects. Meanwhile, Russia negotiated agree- ments to supply the vaccine to countries including Brazil, Mexico and India.

Wuhan Institute of Biological •••

The Wuhan Institute of Biological Products developed an inactivated virus vaccine, which the state-owned Chinese company Sinopharm put into clinical tests. The Phase 1/2 trial showed that the vaccine produced antibod- ies in volunteers, some of whom experienced fevers and other side effects. They launched Phase 3 trials in the United Arab Emirates in July, and in Peru and Morocco the following month. Over the summer, the company later said, the government gave it approval to inject hundreds of thousands of people with its two experimental vac- cines. On Sept. 14, the U.A.E. gave emergency approval for Sinopharm’s vaccine to be used on health care workers.

Sinopharm •••

Sinopharm also began testing a second inactivated virus vaccine, this one developed by the Beijing Institute of Biological Products. After running early clinical trials in China, they launched Phase 3 trials in the United Arab Emirates and Argentina. Over the summer, the company later said, the government gave it approval to inject hundreds of thousands of people with its two experimental vaccines. On Sept. 14, the U.A.E. gave emergency approval for Sinopharm’s vaccine to use on health care workers before Sinopharm shared data indicating it was safe and effective.

Sinovac Biotech •••

The private Chinese company Sinovac Biotech is testing an inactivated vaccine called CoronaVac. In June the company announced that Phase 1/2 trials on 743 volunteers found no severe adverse effects and produced an immune response. Sinovac then launched a Phase 3 trial in Brazil in July, followed by others in Indonesia and Turkey. On September 16, they registered a Phase 1/2 trial of the vaccine for children.

Reuters reported that the Chinese government gave the Sinovac vaccine an emergency approval for limited use in July. Meanwhile, Sinovac has been preparing to manufacture the vaccine, reaching an agreement to supply Indonesia with at least 40 million doses by March 2021. In September, Yin Weidong, the CEO of SinoVac, said the company planned on worldwide distribution of the vaccine in early 2021 — including the United States.

Last updated on October 10, 2020.

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