By Ana Rivas, Peter Loftus and Alberto Cervantes
Some 200 Covid-19 vaccines are in development around the world, according to the World Health Organization, each one promising to protect people from the deadly coronavirus and allow them to go back to work and school.
Now, nearly a dozen are starting or nearing the final stage of testing. Depending on the results, some companies say their vaccines could be greenlighted for use as soon as this year.
A vaccine candidate by Moderna Inc. and one developed jointly by Pfizer and partner BioNTech SE, have shown very positive preliminary trial results and are on track for potential U.S. regulatory clearance by the end of 2020. Both use a novel gene-based technology to provoke an immune response. The University of Oxford and AstraZeneca PLC also have an experimental shot in final-stage testing.
Regulations for vaccine development and rollout vary world-wide. Chinese institutions have four vaccine candidates in the final stages of testing. Russia in August became the first country in the world to approve a state-developed vaccine -- which it did before any advanced clinical testing -- and has since approved a second one with plans for a third under way. Russia, China and the United Arab Emirates are allowing some of their citizens to get vaccinated before clinical trials wrap up.
Many vaccines that show promise in early testing fail during the final round. Trials involving two of the top-runners, developed by AstraZeneca and Johnson & Johnson, were paused or halted because of illness in study subjects -- developments that aren't unusual in large clinical trials -- but the studies have resumed. While final-stage testing may stretch for months or even years to continue to track safety and the durability of protection, positive interim results from Phase 3 may be enough for a vaccine to start getting regulatory approval for mass production and distribution in the meantime. Some of the leading vaccine candidates have started to release interim results, and more are expected in the coming weeks or months.
The Oxford/AstraZeneca vaccine is designed to provide protection by delivering into a person's cells the genetic code for the spikes protruding from the new coronavirus. Then the cells can produce the spike proteins, generating an immune response that would be able to fight off the coronavirus.
Delivering those genetic instructions is a weakened, harmless version of a virus that causes the common cold in chimpanzees. In early testing, the vaccine successfully produced immune responses in humans with only minor side effects.
In early September, AstraZeneca suspended trials globally for its vaccine candidate after a woman in the U.K. experienced illness. The company resumed its U.K. study after investigating the incident, and in October restarted a U.S. study aiming to enroll 30,000 subjects. Other late-stage trials including those in Brazil and South Africa have resumed.
-- Production capacity estimate: AstraZeneca aims to make two billion doses
available world-wide, and has said that one billion may be available this
The Moderna vaccine also uses a gene-based technology to provoke an immune response, though the code it delivers takes the form of messenger RNA. Those molecules, commonly referred to as mRNA, are the body's molecular couriers ferrying DNA instructions for making proteins. The vaccine delivers to cells mRNA for making the coronavirus's spike protein.
Moderna and the U.S. National Institute of Allergy and Infectious Diseases are testing a two-dose shot. The shot has shown to be highly effective at protecting people from Covid-19 symptoms, according to a preliminary analysis of results from final-stage testing announced in mid-November. The 30,000 person trial continues in the U.S.
It was the first candidate to enter human testing in the U.S. The vaccine produced an immune response in early-stage testing and was generally well-tolerated, with minor side effects observed in test subjects. An mRNA vaccine has never been approved for any disease.
-- Production capacity estimate: 20 million doses by the end of 2020; 500
million to one billion doses a year starting in 2021.
The vaccine developed by Pfizer and German partner BioNTech SE also uses mRNA. Phase 3 testing began in the U.S. in July, and expanded overseas to include about 120 sites. The study enrolled 44,000 people. The vaccine reached a development milestone in early November, proving to be more effective than expected at protecting people from Covid-19. Pfizer filed for U.S. regulatory clearance on Nov. 20, and a decision could come by the end of the year.
The timeline suggests the vaccine could go into distribution in December, after U.S. health regulators conduct a review, though it will take months for the companies to make enough doses for the general population.
The U.S. government has agreed to pay Pfizer and BioNTech nearly $2 billion for 100 million doses.
-- Production capacity estimate: up to 50 million doses world-wide by the
end of 2020, and about 1.3 billion by the end of 2021.
China's state-owned Sinopharm is developing two vaccines with the government agencies Wuhan Institute of Biological Products and Beijing Institute of Biological Products. Both are based on an older vaccine-making technique.
The group has entered agreements to conduct testing in several countries, including Pakistan and the United Arab Emirates. The Wuhan Institute has drawn concern over its safety record, including over some of its vaccines for children.
The government says it started what it calls "emergency use" of some of its Covid-19 vaccines on medical workers and border inspection officials in late July. In mid-September, the U.A.E. government said it authorized a Sinopharm shot to be used on its front-line medical workers, becoming the first country outside China to approve emergency use of a Chinese Covid-19 vaccine candidate. Chinese officials have said they aim to make a vaccine available to the public before the end of the year.
-- Production capacity estimate: about 220 million doses a year.
Sinovac, a private Chinese company, began its final-stage trial in July in São Paulo, Brazil, where it is testing its vaccine to take advantage of a higher infection rate. Sinovac has also struck a deal with Indonesian state-owned pharmaceutical holding company PT Bio Farma to make up to 250 million vaccine doses each year for the Indonesian public, according to China's state news agency.
-- Production capacity estimate: about 300 million doses a year at a Beijing
CanSino's vaccine is aimed initially at the Chinese military. Chinese company CanSino developed the shot with the military based on a weakened virus behind the common cold. A Phase 1 study was conducted in March in Wuhan, the early epicenter of Covid-19. The shot got government clearance in June for military use for one year.
-- Production capacity estimate: 100 million to 200 million doses a year
starting in 2021.
Johnson & Johnson is developing a vaccine that uses a weakened form of a common-cold virus, known as an adenovirus. A single dose of this vaccine provoked a strong immune response in early animal testing. The company in September started a 60,000-person global study, which could be the largest late-stage clinical trial of a Covid-19 vaccine. On Oct. 12, Johnson & Johnson said it paused all of its clinical trials because of unexplained illness in a study volunteer, while an independent data-safety monitoring board reviews what happened. The company resumed the large international trial later in October after concluding there was no evidence the vaccine caused the illness.
The study is being conducted at nearly 215 locations in the U.S. and eight other countries where transmission rates are high, including Brazil, Chile and South Africa.
-- Production capacity estimate: one billion world-wide by the end of 2021,
including 100 million doses for the U.S., with an option for an
additional 200 million, and 30 million doses for the U.K., with an option
for an additional purchase of up to 22 million.
The Russian state-owned Gamaleya Research Institute is developing a vaccine based on a combination of two adenoviruses, which it has already tested on volunteers. Russia effectively approved use of the vaccine in early August, though trials are ongoing. In mid-November, the Russian government said early results from a large-scale trial of 40,000 volunteers showed high efficacy against Covid-19 -- 92% -- and no unexpected adverse side effects. The data aren't peer-reviewed.
-- Production capacity estimate: 500 million doses a year, with mass
production starting September 2020.
Novavax's vaccine consists of two shots given 21 days apart that deliver proteins resembling the spike jutting out from the new coronavirus. Researchers hope the proteins will trigger the production of antibodies and immune cells that can fight off the coronavirus.
The shots also contain a component, called an adjuvant, to boost the immune response. In early-stage testing, the vaccine was generally well-tolerated and produced promising numbers of antibodies. The company in late September started a Phase 3 study in the U.K that has been expanded to include 15,000 people. A separate Phase 3 study in the U.S. and Mexico is expected to begin in November.
-- Production capacity estimate: Novavax has said it could produce 100
million doses for use in the U.S., with delivery beginning by the end of
this year, and a global manufacturing capacity of over 2 billion doses
annually when at full capacity in 2021. Novavax said in October it has
experienced some delays from its original timing estimates.
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