under study, optimistic experts hope that a viable vaccine may be ready by the end of 2020.
Other experts caution that the timeline may be unrealistic. Only a small number of those vaccine candidates are being tested on people, and chances are many of the other projects won't survive beyond the laboratory stage.
Even so, vaccine experts point out that funding has been plentiful, many different approaches are under study, and collaborations between small firms developing the vaccines and large drug companies with the capacity to mass produce them all give reason for hope.
An official from the Trump administration said in a conference call with reporters June 16 that they could not guarantee a vaccine will be ready by year’s end.
On that same call, the official, who asked not to be named, said the administration has promised to give the vaccine free to “vulnerable” people who cannot afford it, according to media reports. Officials will use a tiered approach to distribute the vaccine: older people, people with pre-existing conditions, and health care workers.
The U.S. said it would fund and conduct the phase III trials -- the final step to determine how well the vaccine works and if it’s safe -- of three candidates: Moderna Inc., AstraZeneca, and Johnson & Johnson. The Moderna and AstraZeneca vaccines are already being tested in people, while J&J announced Wednesday it will begin its testing in the second half of July.
On June 30, the FDA issued final guidance with recommendations for licensure for companies developing COVID-19 vaccines. Among other recommendations, the FDA says it is important to include diverse populations in all phases of vaccine development, and to have clinical trials large enough to demonstrate the safety and effectiveness of a vaccine. The agency says it would expect a vaccine to prevent disease or decrease its severity in at least 50% of people vaccinated.
The FDA also said it could issue an emergency use authorization (EUA) for a COVID-19 vaccine, but that would be decided on a case-by-case basis after considering all the evidence on the vaccine's safety and effectiveness.
Here are some that are furthest along, with details on how the vaccine works.
Novavax. Results from the phase I study of Novavax's phase I/II clinical trial of its NVX-CoV2373 are expected in July. The vaccine developed by the U.S.-based company uses technology that generates antigens (that stimulate the immune system) derived from the coronavirus spike protein. Two different doses of the two-dose regimen, tested with and without an adjuvant designed to boost the immune response, are being tested. In late May, 130 people ages 18 to 59 were enrolled at two sites in Australia.
Sinopharm. An inactivated vaccine from Sinopharm Wuhan Biological Products Research Institute in China, tested in 1,120 people ages 18-59 in phase I/II clinical trials, produced a strong neutralizing antibody response. When two injections of a medium-dose test vaccine were given 28 days apart, the antibody positive response rate was 100%, the company says. Doses given 14 and 21 days apart produced a response rate of 97.6%.
Clover Biopharmaceuticals. Clover Biopharmaceuticals of China has launched phase I trials in Australia with its subsidiary Clover Australia, using a protein-based vaccine designed to resemble the spike protein on the virus, and also evaluating adjuvants to the vaccine. Adjuvants enhance the immune response and reduce the amount of protein required, so more doses can be produced. According to Clover, 150 healthy adults will be enrolled in the study, with preliminary safety and immune data expected by August. The company aims to conduct a global phase IIb/III study by the end of the year.
Moderna. Moderna's vaccine, mRNA-1273, uses messenger RNA, an approach that does not require a virus to make the vaccine. The messenger RNA, or mRNA, carries instructions for making the spike protein, a key protein on the surface of the SARS-CoV-2 virus that allows the virus to enter cells when a person gets infected. When the vaccine with this instruction molecule is injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the coronavirus. Allowing other immune cells to develop ways to protect you gives immunity.
mRNA-1273 is in phase II of its clinical trial, designed to evaluate safety and effectiveness. Moderna, a biotechnology company working with the National Institute of Allergy and Infectious Diseases, intends to enroll 600 healthy volunteers equally divided into two age groups: 18 to 55, and 55 and older. The company announced on June 11 that it will start phase III of its trial in July with 30,000 volunteers. Phase III, the final clinical trial phase, evaluates effectiveness in a much larger group and compares how well the vaccine works compared to a placebo. Moderna will test a 100 microgram dose and said the company is on track to deliver 500 million doses per year. In mid-May, the company announced that all eight initial trial volunteers given two different dose amounts reached or surpassed the level of antibodies capable of neutralizing the virus.
University of Oxford and AstraZeneca. University of Oxford scientists are partnering with AstraZeneca to develop a COVID-19 vaccine made from a weakened version of a common cold virus, the adenovirus, taken from chimpanzees. The adenovirus is genetically altered so it can’t reproduce itself. The vaccine is combined with genes of the spike protein to trigger production of vaccines against it that allows the immune system to destroy the SARS-CoV-2 virus.
A phase I/II clinical trial began in April in the U.K. to assess its safety and how well it works in more than 1,000 healthy volunteers 18 to 55 years old. Now, recruiting has begun for phase II/III trials, which will enroll up to 10,260 adults and children. For both phase II and III, volunteers will receive one or two doses of either the COVID-19 vaccine or a licensed vaccine that will be used as a control for comparison. In early June, Brazil, hard hit with COVID-19 cases, joined the clinical trials, planning to test 2,000 volunteers there.
After reaching a license agreement with Oxford University and others, AstraZeneca agreed to supply more than 2 billion doses globally, anticipating delivery of 400 million doses before the end of 2020.
The first clinical trial in South Africa and on the continent for a vaccine was announced June 23 at a virtual press conference hosted by the University of the Witwatersrand in Johannesburg. The trial is part of Oxford's larger effort and the first participants will be vaccinated this week.
Pfizer and BioNTech. The companies are testing four vaccines, each using messenger RNA, with a different combination of mRNA to targeted antigens (to produce antibodies). Called BNT162, volunteers in Germany and the U.S. have received the vaccine in a phase I/II clinical trial. This trial will evaluate the safety, ability to give immunity, and the optimal dose of the four candidates in a single and continuous study. Initially they are testing the vaccine on people 18 to 55. On July 1, interim results of one of the four candidates were released. It was tested on 24 people given either a lower dose or a higher dose of the vaccine and on 9 patients given placebo. At day 28, 7 days after the second of two doses were given, all who received both the lower and the higher dose had developed neutralizing antibodies that can halt the virus. The antibodies were produced at or above levels found in the blood of those recovering from COVID-19. Adverse reactions, such as low-grade fever, were more common after the second dose than the first, but were generally short-lived and mild to moderate.
Once a given dose level is proven safe and effective, older adults will be immunized. Pfizer is predicting the production of millions of vaccine doses in 2020, increasing to hundreds of millions in 2021. Manufacturing sites have been identified both in the U.S. and elsewhere.
Inovio. Inovio's vaccine, INO-4800, is a DNA vaccine in phase I clinical trials, with 40 volunteers. The technology uses DNA designed to produce a specific immune response. A handheld smart device uses a brief electrical pulse to open small pores in the skin to deliver the vaccine. Once the DNA is inside a cell, it instructs it to make many copies of the artificial DNA, and this stimulates the body's natural immune response.
Results from the U.S. phase I trial are expected in June, and a phase II/III trial is expected then to begin. Human trials are also expected to begin this summer in China and South Korea. Multiple partners and collaborators are involved, including the Bill & Melinda Gates Foundation, the National Institutes of Health, and others.
CanSino. CanSino Biologics in Tianjin, China, is working with the Beijing Institute of Biotechnology on a coronavirus vaccine using a type of genetically altered adenovirus known as Ad-5. The platform has been used successfully to develop the Ebola virus vaccine.
In late May, researchers reported on results of the phase I safety study, in which 108 people got three doses (low, middle, high) of the vaccine. Most volunteers developed immune responses, but fewer had the neutralizing antibodies experts say are crucial to fight off the virus.
The company launched phase II in mid-April, with over 500 enrolled.
Sinovac Biotech. Sinovac Biotech's vaccine, CoronaVac, uses an inactivated version of the virus. Early results of a Phase II clinical trial released in June show that the vaccine induced antibodies to neutralize the virus after 14 days in 90% of people who received it. The vaccine requires two injections, given two weeks apart, according to the company. No serious side effects have been reported in either phase I or II trials, which included 743 healthy volunteers.
Sinovac will partner with Instituto Butantan in Brazil to launch a phase III trial. The company said it will develop the vaccine for global use.
Imperial College London— Scientists at Imperial College London have developed a vaccine using a concept called ''self-amplifying RNA." The vaccine uses synthetic strands of genetic code, or RNA, based on the genetic material known about the coronavirus. Once injected, that RNA makes copies of itself, then instructs the body's cells to make copies of the spike protein found on the outside of the virus. This is meant to train the immune system to respond to and fight off the coronavirus.
Investigators will launch a combined phase I/II study the week of June 15, initially giving the vaccine to 300 healthy volunteers. They will receive two doses over two visits, separated by a four-week interval. If the vaccine is shown to be safe and to produce an immune response, Phase III trials would be launched later this year with about 6,000 volunteers. Investigators hope the vaccine could be available by spring 2021.
Johnson & Johnson. The company said it expected to start testing its vaccine in people in the second half of July. The vaccine combines genes from the coronavirus with a modified adenovirus. The first trial will include more than 1,000 healthy adults aged 18 to 55 and others 65 and older, and will take place in the U.S. and Belgium.
CureVac. CureVac received regulatory approval from Belgian and German authorities to launch its phase I trial of its vaccine in mid-June; it will test the vaccine in 168 healthy subjects. The vaccine uses messenger RNA technology. According to the company, the messenger substance is programmed with information about one protein of the coronavirus and is injected into the body. The body recognizes the protein as something unknown and triggers immune cells to produce antibodies against it. Depending on the data collected during phase I, the company expects to start the next, larger study in the fall of 2020. CureVac has financial support from the Coalition for Epidemic Preparedness Innovations (CEPI).
Other efforts. The Trump administration chose five companies for Operation Warp Speed, the national program to accelerate the development, making, and distribution of COVID-19 vaccines, treatments, and diagnostics. They are: Moderna, Johnson & Johnson, Merck, Pfizer and BioNTech, and AstraZeneca/Oxford University.
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