Inside the multibillion dollar race for a Covid-19 vaccine

Four years. That’s the fastest a vaccine has ever been developed -- and most take 10 to 15.

But scientists are now racing to do it in under one.

Dozens of research teams around the world are working to develop a vaccine for SARS-CoV-2, the virus that causes Covid-19, using a mix of established techniques and new technologies.

Funding for a vaccine has never been greater, with billions of dollars pouring in from around the world to make a product that could help to control the pandemic -- but the US, China and Europe have invested the most.

Before even the most vulnerable groups can get a shot in the arm from their family doctor, however, a lot of work needs to be done -- and a lot of deals need to be made.

As the coronavirus continues to accelerate unabated, here’s what it will take to bring a vaccine to the masses and how each of the three biggest players are faring in their quest to make it happen as quickly as possible.

The path to a Covid-19 vaccine

Scientists are hoping to deliver a vaccine that protects against Covid-19, and its transmission, by early 2021. In order to do that, the development process has been rapidly accelerated.

A vaccine must go through multiple stages before being green lit for use. An initial research and development stage is followed by a series of pre-clinical and clinical trials (consisting of three phases), and typically each step can take two years or more to complete.

Source: World Health Organization

Pre-clinical: Before testing on humans, researchers usually give the vaccine to animals to assess safety and see if it triggers an immune response. But for some coronavirus vaccines, researchers have been able to speed up normal protocol by testing animals and humans in parallel.

Phase 1: In the first stage of clinical trials, the vaccine is given to a small group of people (usually between 10-50) to check it’s safe.

Phase 2: Then it's tested on several hundred people to further gauge safety, any potential side effects, the immune response and dosage. But a number of coronavirus vaccines are in simultaneous Phase 1/2 trials, which means they’re being tested for the first time on hundreds of people.

Phase 3: In the last stage, scientists give the vaccine to thousands of people across different ages and locations and see how many contract the virus, compared to those who received a placebo. This determines how good it is at reducing new infections -- its efficacy.

Implementation: Regulators then review the trial results to decide whether to approve the vaccine for use, licensing and large-scale manufacturing. Many vaccines also undergo Phase 4 studies after they are approved and licensed.

There are currently 29 vaccines being tested in multiple human trials, running simultaneously around the world. Among these, six vaccines are being tested in seven Phase 3 trials.

Most of the candidates in human trials have either American, European or Chinese financial backing, and some experts believe it will be regulators in one of those places that will be the first to approve a safe and effective vaccine.

American biotechnology firm Moderna was the first in the world to kick off human trials on March 16, just two months after the genetic sequences for SARS-CoV-2 were identified.

Now there are six vaccines in the last stage of human trials (Phase 3) before they seek approval: Three from China, two developed by state-owned Sinopharm and one from private Chinese firm Sinovac Biotech; one from the United Kingdom, produced in partnership between the University of Oxford and AstraZeneca; and two from the US, one by pharmaceutical giant Pfizer, in addition to the candidate by Moderna.

To reach this late stage of trials just six months after discovery is remarkably fast -- it would normally take at least six years, according to Professor Adrian Hill, director of the Jenner Institute at Oxford University.

Record speedto human trials

Progress on a vaccine for Covid-19 has been rapid compared to other viruses, with human trials starting just 67 days after the outbreak began.

Covid-19 (2020) - 67 days

H1N1 (2009) - 89 days

Ebola (2014) - 164 days

SARS (2003) - 323 days

Zika (2015) - 454 days

In the case of SARS and Zika, the epidemics ended before development was complete, and the vaccines are not yet approved for use.

Note: This graphic includes outbreaks declared Public Health Emergencies of International Concern (PHEIC) by the World Health Organization. Speed to trials was calculated using the date of each outbreak's first reported case. SARS -- which was identified in 2003, before the WHO established the PHEIC designation -- is included here because it was a major reason for the creation of the designation.

Source: World Health Organization, National Institutes of Health

In a bid to get something out as soon as possible, some countries are pushing forward vaccines before their efficacy has been proven in Phase 3 trials.

China has already done it, approving an experimental vaccine for use by its military in late June.

Now Russia is touting a vaccine, despite concerns that corners have been cut in its development. On August 11, President Vladimir Putin announced the registration of a vaccine named Sputnik V, the first in the world to be approved for public use. Russia hasn’t released scientific data on its testing, however, and the vaccine was approved the day before the start of Phase 3 trials -- the last and most critical step in the process.

“I hope that the Russians have actually, definitively proven that the vaccine is safe and effective. I seriously doubt that they've done that,” Dr. Anthony Fauci, the director of the US National Institute of Allergy and Infectious Diseases, told ABC News’ Deborah Roberts.

When Americans hear announcements from countries like Russia or China about vaccine development, Fauci said they should remember that the US has very different standards in place.

While that sort of fast-tracking won’t happen in the US or Europe -- where regulators require the full complement of safety and efficacy tests -- several drug companies are pressing ahead and producing stockpiles in case their vaccines get the go-ahead.

AstraZeneca has said it reached agreements with several governments -- including the US and UK -- and other organizations to produce at least 2 billion doses of vaccine, with the first deliveries starting as early as September.

The Biomedical Advanced Research and Development Authority (BARDA), a branch of the US Department of Health and Human Services, is injecting billions of dollars into companies to ramp up vaccine development and manufacturing, including AstraZeneca. It has also inked deals for doses with Novavax, Pfizer-BioNTech, Johnson & Johnson, Moderna and Sanofi and GSK’s joint effort.

This speed is one of the reasons many citizens are wary of getting vaccinated. A recent CNN poll found only 66% of Americans would get a Covid-19 vaccine should one become available.

A protester holds an anti-vaccination sign as Trump supporters in Woodland Hills, California, on May 16, call for the reopening of the state. Credit: David McNew/Getty Images

And, even if everyone does take the vaccine, it almost certainly won’t be 100% effective.

Many vaccines are not even close to 100% effective. For example, the world’s first malaria vaccine — RTS,S or Mosquirix -- was rolled out across Africa last year, despite offering only 39% protection against malaria in children aged 5-17 months. This was considered to be worth it in countries with high rates of the disease when used alongside other interventions.

In comparison, the US Food and Drug Administration has said that a coronavirus vaccine would have to protect at least 50% of vaccinated people to be considered effective. It’s thought that level of efficacy can help stop transmission, especially in combination with other treatments and prevention measures.

Some experts believe that the virus will never really go away and that it may instead become a typical, more manageable infection like influenza.

“This sense that when the vaccine comes, it will be over … it’s a dangerous promise,” said Heidi Tworek, a health communications expert at the University of British Columbia. “The truth is, we've only ever eliminated one disease through vaccines, and that was smallpox and it took hundreds of years.”

Others warn that the coronavirus vaccines that cross the finish line first may not necessarily be the best, and that in the end we are likely to be using multiple vaccines to control the pandemic.

“They’re not all going to come on the market at once,” Robin Robinson, the founding director of BARDA, told CNN. “They're going to be at different times and different amounts.” This was the case for the Ebola epidemic, where a number of investigational vaccines were made available for use after proving to be effective in field trials.

The quest to vaccinate the world is also exposing gaps in the pharmaceutical supply chain. For example, the world has neither enough glass vials for the vaccine, nor the capacity in factories to fill and package them, experts say.

But countries have released extensive funds to fill the void.

The US has already allocated more than $1.5 billion for domestic manufacturing and distribution in order to ensure a vaccine can be produced to scale.

Stages of vaccinemanufacturing

Manufacturing a vaccine is a complex journey that can be broken down into six main steps

 

1

Raw material check:Manufacturers test raw materials that make up the vaccine to ensure quality standards.

2

Vaccine bulk manufacturing:The antigen — the active ingredient of the vaccine, which stimulates an immune response — is grown, harvested and purified at scale.

3

Formulation and quality control:The antigen is mixed with other ingredients to enhance immune response and ensure the vaccine's stability. Each batch is then tested and the antigen verified for sterility.

4

Filling:The batch of vaccine is put into glass vials or prefilled plastic syringes.

5

Packaging:Now in a container, the vaccine is labeled per regulatory requirements and packed for shipping.

6

Release:After testing has been completed for quality assurance, the national regulatory authority gives final authorization to release the vaccine for shipping and distribution.

Note: This is a distilled version of the vaccine manufacturing process.

Source: International Federation of Pharmaceutical Manufacturers and Associations, World Health Organization

The rush to secure supplies is inflaming geopolitical issues too.

The World Health Organization (WHO) has encouraged countries to cooperate in order to ensure fair global access, but some experts believe national interests will get in the way.

Robinson says a precedent was set during the 2009 H1N1 influenza pandemic, also known as swine flu, which the CDC estimates killed as many as 575,000 people worldwide (31 times more than numbers reported by WHO). When a vaccine became available, wealthier countries bought up the supplies, leaving poorer nations at the back of the line, according to WHO and public health experts.

“Many countries closed their borders for exporting vaccines until their own needs were met,” explained Robinson, who was involved in the US response.

Fortunately that strain of H1N1 was much milder than experts had predicted and some older populations showed some immunity to it, meaning the vaccine didn’t play a key role in ending the pandemic.

But Covid-19 is in a different league and is showing no signs of a natural decline.

In the hopes of avoiding a repeat of what happened in 2009, WHO launched the Access to Covid-19 Tools’ (ACT) Accelerator on April 24 in which countries agree to ensure “all people have access to all the tools to prevent, detect, treat, and defeat Covid-19.” But the US and China didn't sign it.

Just over a month later, President Donald Trump announced America’s withdrawal from WHO.

Speaking from the White House Rose Garden on May 29, President Donald Trump announced the US would terminate its relationship with the World Health Organization. Credit: Yuri Gripas/Abaca/Bloomberg/Getty Images

And in another worrying signal, in late June, the US federal government bought up nearly all the global supply of remdesivir available through September -- the first drug shown to be effective in treating severe cases of Covid-19.

It’s feared that the remdesivir agreement, which prioritizes American patients, will serve as a blueprint for distribution of future treatments and vaccines.

United States

The US government has taken an “America First” approach to finding a vaccine. Its Operation Warp Speed initiative is a sprawling effort that’s been likened to the US mission to get a man on the moon. It was launched on May 15 with the aim of delivering 300 million “safe, effective” doses by January 2021.

The mission has selected eight of the most promising vaccine candidates (with one still yet to be named) and supercharged them, supported by the full might of the US government machine -- from manufacturing in federal facilities to distribution by the US Department of Defense.

More than $12.3 billion has already been dedicated to vaccine efforts -- $10.8 billion for vaccine development and procurement, and $1.5 billion for manufacturing and distribution.

Timeline ofUS investment

Operation Warp Speed remains shrouded in secrecy. Here’s what we know about the contracts inked by the US government to secure vaccine doses and shore up the manufacturing supply chain.

Note: Operation Warp Speed investment as of August 11

Source: US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Department of Defense

As part of these contracts, the US has agreed to invest in the manufacturing of hundreds of millions of doses of vaccine, so that if and when one is approved, it is already scaled up for distribution and guaranteed for the American market.

America has been the hardest hit by the virus -- with more than 166,000 deaths, a little less than one-quarter of the global toll -- giving somewhat more urgency to its efforts to secure a vaccine.

But in the process of securing agreements, the US has stirred up political tensions abroad -- particularly in Europe.

When Sanofi, the French pharmaceutical giant, received $30 million in initial funding from BARDA, its CEO indicated the US would be first in line for a vaccine.

The suggestion was met with a backlash. French President Emmanuel Macron weighed in, saying a Covid-19 vaccine must be “public good for the world, and not subject to the laws of the market.” Sanofi later said that its CEO’s comments had been “misinterpreted.”

So, where does that leave Europe?

Europe

The European Commission began extensive funding programs for vaccine research and development at the beginning of the outbreak in January -- and has pledged €350 million ($412 million) so far.

Under its research and innovation program, known as “Horizon 2020,” and with financial help from the European Investment Bank, loans were also set up to aid vaccine efforts.

As part of that funding, the EU has lent €75 million ($88 million) to German biotech company Curevac and €100 million ($117 million) to BioNTech, another German firm -- both of which have vaccine candidates in human trials.

The EU has also begun exploring options for procurement of a future vaccine, pledging to use a significant part of a €2.7 billion ($3.2 billion) emergency fund to bulk buy doses for all EU members and help subsidize costs for developers in exchange for doses.

Comparison ofEU and US vaccine investment

The EU has earmarked about €3.05 billion ($3.5 billion) for vaccine research, development and procurement, about one-third of the $10.8 billion in funds allocated by the US to the same efforts.

Note: The EU figure is a combination of Horizon 2020 and the Emergency Support Instrument, the bloc's two key vaccine plans. The US figure represents all BARDA funding.

Source: European Commission, US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Department of Defense

In effect, the Commission is taking a gamble and pre-ordering future vaccines, agreeing to pay for the cost of production up front in exchange for the right to buy it at a specific quantity and price when it is approved. It’s not that dissimilar from the US approach, in which BARDA is funding various vaccine efforts, and then agreeing on dosages with select developers.

Sanofi was among the first candidates to participate. In July, the French multinational began discussing a contract with the Commission, which would provide 300 million doses for all EU member states.

So far, the EU has backed, or provisionally agreed to back, the purchase of at least six vaccines.

President Emmanuel Macron visits the French drugmaker Sanofi Pasteur's vaccine unit in Marcy-l'Etoile, France, on June 16. Credit: Gonzalo Fuentes/Pool/AFP/Getty Images

In perhaps the starkest example of what the post-Brexit world looks like, the UK has been notably absent from EU plans.

It opted out of the EU vaccine program in July, citing concerns over cost delays.

Instead, the UK government has gone on a securing spree of its own, locking down at least 380 million doses from a variety of developers including Oxford-AstraZeneca, BioNTech-Pfizer, Valneva, Imperial and, later, Sanofi-GSK.

UK investment in vaccine research has focused on British efforts. In May, the UK announced £84 million ($109 million) of government funding towards the British vaccine candidates at Oxford University and Imperial College London. The bulk of the funding, £65.5 million ($85.5 million), will go towards the Oxford candidate.

The Oxford vaccine -- among the most closely-watched and highly-anticipated efforts -- has also received investments from the EU and the US. But the British government has secured early access to around 100 million doses of the vaccine beginning in September.

Europe’s Inclusive Vaccines Alliance (IVA) -- spearheaded by France, Germany, Italy and the Netherlands -- has struck a deal for up to 400 million doses, with deliveries starting by the end of 2020 to participating European countries.

The US has made a similar deal with AstraZeneca for 300 million doses, delivering as early as October.

China

If the US and Europe have merely hinted that they’ll prioritize their people first for vaccines, China has made no secret of its plan to do exactly that.

President Xi Jinping told the World Health Assembly, the decision-making body of WHO, in May that Beijing would help provide a vaccine globally, but only after it had been deployed in China.

US health officials say America, the G7, the EU and the ACT Accelerator are collaborating closely on vaccine development -- but not China. “I believe they're just -- they're doing their own thing,” US HHS Secretary Alex Azar has said, referring to China.

China has a shorter history of vaccine expertise compared to the US and Europe, but it has size on its side. It is the world’s largest producer and consumer of vaccines and can supply more than 1 billion doses of a vaccine annually from 40 manufacturers across the country, according to the China Human Vaccine Industry Report, 2018-2022.

Chinese President Xi Jinping assesses the progress on vaccine and antibody research during his visit to the Academy of Military Medical Sciences in Beijing on March 2. Credit: Xinhua/Ju Peng via Getty Images

Of the 29 vaccines currently in human trials globally, nine are from China -- the most from any country by a long shot. And three of the six vaccine candidates in late-stage trials are being developed by Chinese companies Sinovac and Sinopharm.

The chairman of Sinopharm has told Chinese state media that it could have a vaccine ready for public use by the end of the year.

Some Western health experts have expressed concern, however, about China’s safety record due to past vaccine scandals.

But Beijing is determined to shake this image.

A government paper published in June said Chinese scientists and officials were collaborating with international partners, medical institutions and experts to ensure transparency around their vaccine efforts. It also said that although vaccine research and development had been dramatically accelerated, Beijing was adhering to safety principles.

What happens next

But the question remains: Will leaders -- the world over -- be able to respond and buy the vaccine for their own populations if one of the big three efforts succeeds? And will poorer nations once again be left behind?

It is this concern that prompted Dr. Seth Berkley, CEO of Gavi, the Vaccine Alliance, to call for an international accord to ensure poorer countries get access to the vaccine.

The best-case chance of getting a vaccine, according to Berkley, is adopting the collaborative approach that was used in the race for an Ebola vaccine -- a process which began in the Canadian Public Health laboratory, was transferred to an American biotech firm, then an American multinational company, and finally to a German company for manufacturing.

“That’s the way things get done,” Berkley said.

A lab technician looks at a bottle containing a reagent, before performing vaccine tests at Sanofi's laboratory in Val de Reuil, France, on July 10. Credit: Joel Saget/AFP/Getty Images

Restricting the effort to a national lab or set of scientists or certain company won’t deliver the best vaccine -- and it certainly won’t allow it to be distributed to all -- he added.

There are some promising signs of international cooperation. Aside from WHO’s ACT Accelerator initiative, the Coalition for Epidemic Preparedness Innovations (CEPI) -- a nonprofit co-founded by the Bill & Melinda Gates Foundation to fund the development of vaccines against emerging diseases -- has injected capital into multiple vaccine efforts with the explicit goal of meeting “global demand for a vaccine as quickly as possible.”

Those efforts, combined with those from organizations such as Gavi and the International AIDS Vaccine Initiative, aim to deliver safe and effective vaccines to everyone who wants one.

And even if countries who cross the finish line first do start by protecting their own populations, Robinson believes the world is cooperating the best it can in the face of an unprecedented health emergency.

“I think at this point everyone is saying the right things,” he said.

“When we actually have vaccine candidates that are approved by the regulatory authorities to go forward, then that may be a different thing.”

News Courtesy: www.cnn.com