Researchers worldwide are working around the clock to find a vaccine against SARS-CoV-2, the virus causing the COVID-19 pandemic.
→ Article updated 2-10-2021
Experts estimate that a fast-tracked vaccine development process could speed a successful candidate to market in approximately 12-18 months – if the process goes smoothly from conception to market availability.
Can we trust it?
Confidence in a COVID-19 vaccine is essential and it is likely to be shaken before the finish line is reached.
♦ There is a real concern that the Trump administration will apply pressure on the FDA to cut corners to try and get a vaccine approved before the elections simply to help Mr. Trump at the polls.
Commissioner Stephen Hahn has said this will not happen. However, his agency has been blasted for granting an Emergency Use Authorization (EUA) for the malaria drug hydroxychloroquine, an approval that seems mainly to have been designed to avoid embarrassing the president, who endorsed the drug as a treatment without any evidence. ►That approval was later revoked.
Dr. Peter Marks, director of the FDA Center for Biologics Evaluation and Research, oversees vaccine approval. He has suggested they may issue an EUA in a matter of weeks. That would permit the vaccine to be tried beyond controlled trial recipients.
• Most experts suggest this would be risky especially given that the current leading vaccine candidates are gene-based vaccines. A new type of vaccine that has never before been approved for use in humans.
“The first vaccines that come along may be slightly disadvantaged compared to the ones that come along later,” said Marks.
It sounds like he is trying not to say something. Perhaps we should expect an EUA approved vaccine will not have all the kinks worked out or negative effects understood at first but we will learn more as it is tried in more people.
In the past most people would not agree to be the first to get these EUA vaccines but with the severity of Covid-19 many people are expected to step forward and roll up their sleeves.
Who’s doing what?
There are now 148 vaccine candidates being worked on worldwide, with 17 in human clinical trials. Most are gene-based instead of using traditional approaches, such as those that have been employed in influenza vaccines for more than 70 years.
Gavi – The Vaccine Alliance is an excellent site to visit to keep up on the progress around the world to find a vaccine to fight SARS-CoV-2.
♦ Most gene-based candidates are modified RNA (mRNA) based rather than DNA. Research shows that mRNA vaccines may be better than DNA-plasmids at mobilizing the immune system to create antibodies.
There are drawbacks to mRNA vaccines. They are less stable than DNA-plasmid vaccines. Common enzymes in the body can quickly degrade mRNA vaccines. Heat can ruin them, too. mRNA vaccines must be kept frozen or refrigerated, which creates logistical hurdles, particularly in poorer countries. DNA-plasmid vaccines are stable at higher temperatures.
• For a vaccine to be effective it must be able to infect human cells and delivers the blueprint it is carrying. mRNA vaccines can more easily penetrate cells and deliver their instructions.
♦ Although labs have created several gene-based vaccines for other viruses, not one has been commercialized for a human illness.
If an effective gene-based vaccine can be developed in a year, it will be the fastest vaccine development in history. Compared to the Ebola vaccine, which was fast-tracked and still took five years to reach widespread trials.
Vaccines are difficult to make and historically more vaccine projects fail than succeed. Only about 15% of vaccine candidates will make it out of the lab and into clinical trials.
The vast majority of vaccine candidates will fail, but by having a large portfolio of potential candidates the possibility of two or three successful ones is greatly improved.
♦ The US is spending more than $13 billion on this goal and pursuing an aggressive strategy to achieve it in the shortest time possible.
The money being directed at vaccine makers is also geared to helping firms scale up development and mass manufacturing.
♦ Many of the contracts are shrouded in secrecy. Watchdog groups are already crying foul over the way large sums of taxpayer dollars are being funnels to politically connected companies.
In effect, the government is subsidizing the creation of a product that may not work. The strategy, which is also being employed by governments elsewhere, is necessary to help shave months off the development time for vaccines.
Operation Warp Speed
The push for rapid development of vaccines started in April with Operation Warp Speed (OWS). OWS is a partnership between Health and Human Services, the Department of Defense, an alphabet soup of health-related agencies and the private sector. The goal is to deliver 300 million doses of a vaccine by January.
• Within OWS, the US National Institutes of Health (NIH) has partnered with more than 18 biopharmaceutical companies to accelerate development of drug and vaccine candidates for COVID-19.
The COVID-19 Prevention Trials Network (COVPN) has also been established, which combines clinical trial networks funded by the National Institute of Allergy and Infectious Diseases (NIAID): the HIV Vaccine Trials Network (HVTN), HIV Prevention Trials Network (HPTN), Infectious Diseases Clinical Research Consortium (IDCRC), and the AIDS Clinical Trials Group.
♦ The US government is choosing three vaccine candidates to fund for Phase 3 trials under OWS.
A fourth candidate by Novavax, Inc. of Gaithersburg, Maryland might reach Phase 3 testing by the end of this year.
♦ The US government is also providing funding to Johnson & Johnson, Merck and Sanofi SA and GlaxoSmithKline to help support their efforts.
OWS is also buying medicines known as antibody therapies, and is part of a broader government strategy to accelerate the arrival of drugs and diagnostic tests.
• Although OWS is described as a public-private partnership, the US government is putting up the majority of the cash and taking on a lot of risk.
The scale of the effort is so large that it has also been necessary to step up the national production of syringes and vials.
As part of this effort, the government at the end of June bought up most of the supply of the drug Remdesivir from the manufacture Gilead. This caused an international outrage.
• The purchase of Remdesivir caused alarm in many other rich countries, which fear that a drug that improves recovery time will be hard to obtain for their own patients.
The move to corner the supply of this drug looked particularly bad abroad because the trials necessary to show that the drug worked involved patients in Germany, Greece, Japan, Korea, Spain and Britain.
• American efforts to gain access to German and French vaccines have also sparked controversy in those countries.
► On July 7th, OWS signed a deal worth $450 million with Regeneron. This acquired most of Regeneron’s supply of a promising experimental therapy, REG-COV2, for the next three months. If it turns out to work, most other countries will be unable to get a hold of it.
Regeneron’s drug is expected to finish trials by the end of the summer. If it works, the federal government could be sitting on most of the world’s supply of the drug.
REG-COV2 is not without controversy, as it is derived from human fetal tissue dating back to an aborted fetus in Holland sometime before 1973. A cell line has been grown from the fetus's kidney and used widely in medical research these many years.
♦ October 7th, Regeneron submitted a request to the FDA for an Emergency Use Authorization (EUA). REG-COV2 is a cocktail of two monoclonal antibodies. It was recently given to President Trump.
Moderna and NIH
Moderna has a vaccine candidate what is about to begin Phase 3 testing. Moderna’s vaccine was developed in collaboration with the National Institutes of Health (NIH).
The vaccine is known as mRNA-1273. The trial, which will be conducted at US clinical research sites, is expected to enroll approximately 30,000 adult volunteers who do not have COVID-19.
♦ The Moderna vaccine is a new kind of vaccine based on pieces of modified RNA (mRNA) that are enclosed in a nanocapsule and injected into someone's arm. Currently, there are no mRNA vaccines approved for human use.
The mRNA contains instructions to make a protein found of the outer surface of the coronavirus. This protein is what stimulates the immune system to make antibodies against the virus.
Moderna has been given $536 million by the US government, directed toward scale-up of production.
Oxford and AstraZeneca
AstraZeneca is partnering with Oxford University on a vaccine. Phase 3 testing is being funded by OWS.
• The Oxford vaccine is in Phase 3 clinical trials in more than 10,000 people from across the UK, including children and the elderly. The vaccine is also being tested in Brazil and has just started in South Africa, the first COVID-19 vaccine trial in Africa.
With support from the Coalition for Epidemic Preparedness Innovations (CEPI), AstraZeneca will manufacture 300 million doses of this coronavirus vaccine candidate in anticipation of the vaccine proving to be both safe and effective.
♦ The Oxford vaccine is based on a harmless, weakened version of a common cold virus, or adenovirus that causes infections in chimpanzees. Many people will be frightened to learn “weakened” not “dead." Some experts also worry an adenovirus itself could replicate inside the body and cause disease.
These types of vaccines are referred to as ‘adenoviral vector vaccines.’ They rely on genetically engineered viruses to introduce a weakened Sars-CoV-2 gene into the human body with the objective that it will cause the immune system to produce antibodies and attack the virus.
♦ Adenoviral vector vaccines have been tested in far more humans than mRNA vaccines. So far, no adenoviral vector vaccines have demonstrated they can prevent diseases in humans. One such vaccine is commercially available for use in dogs: a rabies vaccine.
If it is safe and effective, the first doses are expected to be available in late 2020.
Pfizer and BioNTech
Two vaccine candidates for COVID-19 under development by Pfizer and a German partner have received fast-track designation from the Food and Drug Administration.
♦ Pfizer is also working with modified messenger RNA (mRNA) vaccine candidates, much like what Moderna is developing.
Pfizer did not accept funding from the US government for their vaccine development.
They say it was so they would have greater freedom in the development. Analyst also believe this was so their pricing would not be hampered by government red tape.
♦ That strategy may be paying off handsomely. The US government just signed a $1.95 billion contract with Pfizer to produce at least 100 million doses of their experimental COVID-19 vaccine, if it receives approval or emergency use authorization from the Food and Drug Administration.
Both vaccines are currently in Phase 1 or 2 development, and the companies said they may start a Phase 2b or 3 studies as early as the end of July. Phase 3 would enroll up to 30,000 subjects. If all studies prove successfully, they hope to ask for EUA approval in October.
Novavax is a Maryland based biotech firm. Novavax’s vaccine is a bit more uncertain at this time.
Their vaccine may start Phase 2 trials sometime in August. Still, the US government has made a major financial commitment to this company.
♦ Novavax is using a nanoparticle technology platform to generate antigens from the protein found on the spikey outer shell of the coronavirus. They are calling it a prefusion protein nanoparticle vaccine. There seems to be a lot of “proprietary” surrounding this candidate.
Novavax’s vaccine is a “subunit” vaccine - which sends copies of the virus’s spike protein directly into the body to stimulate an immune response.
♦ This is an established vaccine technology currently being used against diseases such as HPV, Hepatitis B and Shingles.
• In July, they were awarded a $1.6 billion contract to support clinical trials and expansion of their manufacturing capacity.
This comes just after a $70 million agreement with the company to manufacture components of the vaccine in the US and supply 10 million doses for trials.
The company has also raised $200 million from selling stock to an investment fund.
• In return for this latest large infusion of Uncle Sam’s dollar, Novavax will supply the US government with 100 million doses of their investigational vaccine. This is likely to be enough to vaccinate 50 million people. This all assumes their vaccine is safe and effective.
Initial data from Phase 1 trials looks very encouraging. Phase 1 trials are expected to be completed by the end of July.
► August 4, 2020 Novavax announces positive Phase 1 data with mostly mild side effects.
Phase 2 trials are expected to begin in August.
• On January 28, 2021, Novavax released data on a small Phase 2b trial of about 4,000 people in South Africa. The data suggested the vaccine went from 89% effective against the original COVID-19 virus to about 50% for the new South African variant.
The Phase 2b trial was very small so it is not yet clear how much can be concluded. The vaccine results are disturbing. But the data from the placebo part of the trial is alarming. That data suggests that individuals who had previously been infected with COVID-19 had no protection against the new South African strain.
♦ They hope to start Phase 3 trials, involving roughly 30,000, in the third quarter of the year. Should all go well, we are looking at the first part of next year before the general public will be offered this vaccine.
► Phase 3 trials began in September in the United Kingdom with another one to start in the United States at the end of December.
• On January 28, 2021, Novavax announced early results from a British trial consisting of about 15,000 people, the vaccine had an efficacy of 89%.
There might be a little snag with Novavax as far as who gets first dibs on a successful vaccine. Novavax received $388 million from the Coalition for Epidemic Preparedness Innovations or CEPI for manufacturing support. As a condition for the funding, the Covax Facility has the right of first refusal of vaccines.
• The Covax Facility is an entity established by CEPI, Gavi, the Vaccine Alliance, and the World Health Organization to secure COVID-19 vaccines for non-producing countries.
Novavax recently purchased a production facility in the Czech Republic. The company believes this facility will be able to produce 1 billion doses of vaccine a year, and thereby meet Novavax’s CEPI commitment.
Johnson & Johnson
Johnson & Johnson recently released results of a vaccine candidate, Ad26.COV2.5, which appears to protect a group of monkeys that were vaccinated, and then later deliberately exposed to the virus that causes COVID-19.
♦ The company is aiming to have its single-dose vaccine candidate available for broad use early in 2021. They are also testing two backup vaccine candidates.
J & J has a good track record on vaccines, developing ones for HIV, Ebola and the Zika virus over the last decade.
• OWS provided J & J $456 million in March to support their vaccine candidate’s development.
J & J is working with recombinant DNA. They insert a DNA blueprint into a common cold virus. This is an adenoviral vector approach.
Adenoviruses are good at getting into cells. Past work shows that the human immune system readily recognizes some adenoviruses and attacks them before they can sneak in. J & J believes their version can avoid detection.
Phase 1/2a human clinical trials of vaccine candidate, Ad26.COV2.S, has just started in the US and Belgium.
► January 29th, 2021, Johnson & Johnson announced that in a large-scale trial (44,000 people) their single-dose vaccine showed some mixed results. The vaccine's level of protection against moderate to severe COVID-19 was 72% in the U.S., 66% in Latin America and drops to 57% in South Africa. These numbers may seem underwhelming but by comparison to the annual flu shot, which ranges from 40 - 60% effective, the J & J shot can still play a major role in stopping the spread of COVID-19.
• On February 4th, 2021, Johnson & Johnson applied to the FDA for Emergency Use Authorization (EUA). If approved, the vaccine could be ready for use in the U.S. by the end of March.
Merck recently jumped into the coronavirus vaccine race by acquiring two coronavirus vaccine candidates.
One is a vaccine using similar technology Merck uses for its successful Ebola vaccine. It is being developed in partnership with the International AIDS Vaccine Initiative (IAVI), a nonprofit that was originally set up to push forward HIV vaccines.
For the second vaccine project, Merck is acquiring Themis, an Austrian company that licensed a platform based on the established measles vaccine and developed at the Pasteur Institute.
The vaccine contains a weakened version of the virus that causes measles, which Pasteur scientists showed could serve as a carrier for genes from a wide range of pathogens, including Covid-19.
They add a gene specific to the spike protein from SARS-CoV-2 to this attenuated measles virus. Clinical trials start in July or August.
• The US government awarded Merck $38 million through the Biomedical Advanced Research and Development Authority (BARDA).
Sanofi SA and GlaxoSmithKline
The U.S. government will pay up to $2.1 billion to Sanofi SA and GlaxoSmithKline PLC to fund the development of a coronavirus vaccine and guarantee supply of 100 million doses, if proven safe and effective in clinical trials.
♦ Paris-based Sanofi is leading development of the vaccine. They plan to start initial clinical trials in September and move into late-stage studies by the end of this year.
Sanofi said it could apply for regulatory approval in the first half of next year.
Sanofi’s coronavirus vaccine relies on a protein-based technology that the company already uses to produce an influenza vaccine. It is similar to a technique used by another company, Novavax.
Who will take it?
There is a concern over anti-vaxxers and how they will react to any new COVID-19 vaccine.
A poll in May found that half of Americans would take a vaccine. Even if a COVID-19 vaccine is only 50% effective, and taken by less than half the population, experience with flu shots suggests that it would be life-saving.
A bigger concern, though, is whether a vaccine would get to those most at risk from COVID-19.
Racial disparities already exist in flu-vaccination rates, with lower coverage among Blacks and Hispanics as compared with the vaccination rate of Whites.
Most American’s are expecting the vaccine to be free. Even so, the manufacturer will have to be paid by someone. Uncle Sam?
At some point there will need to be a discussion about profits and how much is morally acceptable.
Almost every company is going to be employing proprietary technology or proprietary adjuvants to enhance immune responses.
Proprietary comes with a price.