The research and testing that goes into creating a new vaccine normally takes years, a process world leaders are hoping can be safely and effectively shortened to 18 months or less. File Photo by John Keith/Wikimedia Commons
May 29 (UPI) -- As the worldwide death toll from the novel coronavirus continues to rise, scientists across the globe have spent the year racing to find a vaccine.
It often takes years to secure funding, research and develop a vaccine candidate, test it on humans and get regulatory approval. And that's all before pharmaceutical companies can begin the task of actually manufacturing millions of doses for distribution.
A New York Times analysis indicates that under a normal timeline, a COVID-19 vaccine wouldn't be ready for distribution until May 2036.
But with the number of dead growing worldwide, and the global economy struggling under mitigation efforts, world leaders have been eager to speed up the process.
U.S. President Donald Trump in May announced Operation Warp Speed, an effort to shorten the time frame in which a vaccine goes from concept to distribution. He'd called for a vaccine to be available for use within about 18 months, a goal some experts warned was too optimistic.
More than 100 vaccine trials are ongoing, but scientists have hit that 18-month goal early -- one vaccine, from Moderna, was approved in early December by the U.S. Food and Drug Administration and is now being distributed.
Here are a handful of the more notable research efforts underway:
BioNTech and Pfizer
Pfizer partnered with German company BioNTech in early May to administer a vaccine candidate known as BNT162 on human test subjects. Tests were carried out at New York University, the University of Maryland and Cincinnati Children's Hospital as part of a Phase I/II clinical trial.
The initial trial is designed to determine the safety, immunogenicity and optimal dose level of four versions of Pfizer's vaccine candidate, which uses "messenger DNA" to spur the body to produce antibodies that fight the coronavirus.
All 24 participants in an early trial of the vaccine candidate generated antibodies against the coronavirus that causes COVID-19, the companies reported on July 1. The level of antibodies needed to provide immunity will be determined in a larger safety and efficacy trial scheduled to start this month.
They company also said they're preparing a large-scale rollout that will produce millions of vaccine doses this year and hundreds of millions next year.
The companies said on July 20 that one of four vaccine candidates they are testing, BNT162b1, produced "robust" T cell and antibody responses in patients participating in the study.
On Nov. 9, the two companies announced that a stage 3 trial showed their vaccine can block infection with the coronavirus. Just 10% of the 100 participants who tested positive for COVID-19 had received the vaccine rather than a placebo, the trial results showed.
The companies said an interim analysis of the trial data shows the two-dose vaccine provides protection beginning seven days after the second dose and 28 days after the first dose. They will now seek an emergency use authorization from the FDA once "the required safety milestone is achieved" -- which may happen before the end of November.
Pfizer officially requested an emergency use authorization from the FDA on Nov. 20, which the company said could allow it to start shipping its vaccine to high-risk groups by the middle of December.
The British government on Wednesday became the first Western nation to approve a COVID-19 vaccine, with Pfizer receiving the approval and officials expecting it to become available as soon as next week.
Pfizer's vaccine was approved by the U.S. government on Dec. 11 and distributed across the country over the weekend, with the first shots given to front-line health workers on Dec. 14.
Moderna and NIAID
Moderna said on May 18 that a Phase I trial of its mRNa-1273 possible vaccine indicated a "potential to prevent" COVID-19. The vaccine succeeded in producing antibodies to attack the virus in all 45 test subjects in quantities "of the magnitude caused by natural infection."
It announced on June 11 that it plans to enter its third and final clinical stage of testing in July using 30,000 participants.
Moderna is conducting the trial in partnership with the U.S. National Institute of Allergy and Infectious Diseases at the National Institutes of Health. The company said it plans to deliver between 500 million and 1 billion doses per year starting in 2021 in collaboration with drugmaker Lonza.
Moderna's Phase I results announcements caused stocks to soar after a tumultuous two months in the markets.
On July 15, Moderna announced the Phase 1 trial saw a "rapid and strong" immune response against COVID-19, and that the vaccine was "generally safe and well-tolerated" among the 45 study participants.
Moderna announced on July 27 that it started a 30,000 patient Phase 3 trial for it's vaccine candidate, with the first study participants already having been dosed. The primary endpoint for this trial, titled COVE, is prevention of COVID-19.
An update on data from the Phase I trial on Aug. 25 showed older adults that received the vaccine displayed higher levels of COVID-19 antibodies than patients who had recovered from it.
Moderna on Nov. 16 published an interim analysis of data in its Phase III trail showing its COVID-19 vaccine candidate is 94.5% effective at preventing infection. No serious side effects have been detected in study participants.
The company's CEO said it will pursue an emergency use authorization from the FDA later this month once it has finished compiling safety data on the vaccine.
On Nov. 30, Moderna said it would be applying to the U.S. Food and Drug Administration for an emergency use authorization after further trial data showed the company's vaccine is 94% effective.
With an expected FDA approval, the vaccine could become available within weeks, officials said.
The FDA on Dec. 15 said in a 45-page report that Moderna's vaccine is safe and effective enough for use. The agency's Vaccines and Related Biological Products Advisory Committee meets this week to consider approval of an emergency use authorization for the vaccine.
Oxford University and AstraZeneca
Oxford Vaccine Group and the Jenner Institute have entered Phase I/II human trials for their potential vaccine AZD1222. Researchers are enrolling volunteers to test the vaccine, which is made from a weakened version of the adenovirus.
In May, Oxford announced it received more than $1 billion from the Biomedical Advanced Research and Development Authority, a branch of the U.S. Department of Health and Human Services. The British government has also supplied $79 million for the AstraZeneca/Oxford collaboration.
AstraZeneca plans at least 400 million doses and has lined up manufacturing capacity for 1 billion doses with first deliveries set for September.
Oxford and AstraZenaca on July 20 announced that their vaccine candidate, also referred to as ChAdOx1 nCoV-19, induced an immune response in 91 percent of study participants within 28 days of receiving a shot.
Australian Prime Minister Scott Morrison on Aug. 19 announced a deal with AstraZeneca to provide enough doses for every person in Australia to receive one, should the vaccine be approved.
AstraZeneca on Sept. 1 announced it was starting a Phase III trial in the United States, with the goal of enrolling up to 30,000 adults in order to assess safety, efficacy and immunogenicity of AZD1222. The company also has separate late-stage trials ongoing in Britain, Brazil and South Africa, with trials planned for Japan and Russia, which will bring the total number of participants to 50,000, officials said.
Global trials of the vaccine candidate were paused on Sept. 9 after an unexplained illness in a participant. The company said an independent review of the illness was being conducted, and Matt Hancock, Britain's health secretary, said the concern should not yet be considered a setback.
The company said on Nov. 5 that late-stage trial results are expected for its vaccine before the end of 2020, raising hopes that the vaccine could be available by the end of the year or early 2021.
AstraZeneca on Nov. 23 announced its vaccine has 70% efficacy, based on an interim analysis of clinical trial data. The company said it has tried a number of dosing regimens, including one that reaches 90% efficacy within one month of vaccination.
The company is currently preparing to submit for regulatory approval and emergency approval from the WHO, with a full analysis of the interim trial data also being submitted to a peer-reviewed journal.
Imperial College and British government
British researchers announced June 16 plans to start Phase II human trials for a potential vaccine. Three-hundred healthy participants will receive two doses of the vaccine candidate.
The candidate uses synthetic strands of genetic code called RNA. This genetic material will self-replicate once injected into the test subject, and will instruct the body's cells to create copies of the virus' spiky protein.
If the Phase II trial is successful, researchers will be move on to Phase III involving 6,000 test subjects.
Imperial College London's research is funded by $50 million from the British government.
Johnson & Johnson
In late July, Johnson & Johnson said its lead candidate, Ad26.COV2-S, produced a "robust immune response" in monkeys during trials. The trials in animals came simultaneously while the company tested the experimental vaccine in humans in both single and double doses.
The experimental vaccine is vector-based and uses an Ad26 virus to take the coronavirus spike protein gene to human cells. The cells then use the spike gene to replicate the coronavirus proteins and protect themselves from the virus.
The company said it plans to begin Phase III trials in September. It has also identified two backup options.
It plans to use funding from the federal Biomedical Advanced Research and Development Authority to scale up manufacturing with the goal of producing more than 1 billion doses.
Johnson & Johnson plans to collaborate with Emergent BioSolution to manufacture the vaccine.
The company said on August 5 that it has come to an agreement with the U.S. government to provide 100 million doses of its vaccine after it is approved on a "not-for-profit basis."
CanSino Biologics and China's Institute of Biotechnology
This Ad5-nCoV vaccine candidate produced in China was the first to be tested in humans -- a study of which found that it appears to be safe and able to generate an immune response against COVID-19.
It uses a weakened common cold virus, adenovirus, which infects human cells but is incapable of causing disease, to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. They then produce the spike protein and allow the immune system to create antibodies to fight the coronavirus.
A study, released May 22, found that low, medium and high doses of the vaccine produced some level of both COVID-19 antibodies and T-cell response.
The vaccine will need to pass through Phase II and Phase III clinical trials in humans with similar positive results before widespread use.
Chinese officials on June 29 approved the vaccine candidate for immediate use by military personnel, though it was unclear how many of the 2.2 million members of China's military would receive it.
On July 20, results from a Phase II trial showed 95% of patients receiving a higher dose and 91% given a lower dose had immune responses to the vaccine candidate within 28 days of receiving the shot. About 70% of participants in the study reported mild side effects, researchers reported.
Sinopharm and China National Pharmaceutical Group
Sinopharm on Aug. 18 announced it has started international Phase III trials for it's coronavirus vaccine candidate, and plans to enter the screening and approval phase at an accelerated rate.
Phase I and II trials of the potential vaccine showed it is safe and generated an immune response, according to a paper published earlier in August.
Sinopharm said it expects the vaccine to be approved and publicly available by the end of December.
Chinese biopharmaceutical company Sinovac Biotech began Phase II clinical trials of its CoronaVac vaccine candidate in May. The study is evaluating the immunogenicity and safety of the potential vaccine in a larger population.
In preclinical studies in macaque monkeys, the inactivated vaccine proved to be safe and provide immunity.
The company is constructing its own production plant to manufacture up to 100 million doses of the vaccine each year.
Sinovac received $15 million on May 22 to accelerate the development of CoronaVac.
Sanofi and GlaxoSmithKline
French pharmaceutical giant Sanofi and GlaxoSmithKline partnered together in April to create an adjuvanted vaccine, a type of vaccine that requires a smaller amount of vaccine protein per dose, allowing more doses to be produced more quickly.
Sanofi paired its S-protein COVID-19 antigen -- based on recombinant DNA technology -- with GSK's adjuvant technology to create the vaccine candidate.
This vaccine is in the pre-clinical phase, but GSK announced May 28 that it plans to make 1 billion doses of a vaccine adjuvant system through 2021.
Merck and IAVI
This vaccine candidate, now in pre-clinical studies, is being designed and engineered by International AIDS Vaccine Initiative scientists. Merck will manage its regulatory approval process. It uses the same recombinant viral vectoring, or rVSV, technology as Merck's successful Ebola Zaire virus vaccine, Ervebo.
Merck is also working on two other vaccines -- one with biotechnology company Themis and another with Ridgeback Biotherapeutics.
Biotechnology company Novavax announced Aug. 4 that a Phase I clinical trial of a potential vaccine called NVX‑CoV2373 generated favorable immune response results. Researchers began a combined Phase I/II preliminary immunogenicity and safety trial.
The vaccine candidate produced neutralizing antibodies in the subjects at a higher rate than observed in people who have recovered from COVID-19. Novavax said immune response for those who received an adjuvant was also stronger.
On Aug. 17, the company announced it was starting a Phase II trial for it's vaccine candidate in South Africa, where they will enroll 2,600 participants. The company also said it plans to start a 1,500-participant Phase II trial in the United States and Australia "in the near future."
Novavax on Sept. 3 published results from the Phase I trial of its vaccine candidate showing it is safe and well-tolerated by patients. The vaccine produced immune responses greater than that found in convalescent plasma and induced T cell responses in patients during the randomized, placebo-controlled trial, the company reported.
Visitors wear face masks as they tour the Whitney Museum of American Art as it reopens on September 3. Photo by John Angelillo/UPI | License Photo