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Why does vaccine development take so long?

Why does vaccine development take so long?


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The main principle behind a vaccine is to take a deactivated virus, "show" it to the immune system so it can "learn" how it looks like, so if and when the real virus does attack us, our immune system is already prepared for it. Vaccines have been developed using this idea even in the 1880's.

If that's the case, why does it take so much time and effort to develop a vaccine, for example, against covid-19? (and why are there several variants with different measures of reliability?) Is it only about balancing how strongly we damage the original pathogen, too much damage and our body might not learn the correct identifiers, and to little damage and it might still be active enough to cause the disease?


Roni Saiba's answer does a good job of explaining what goes into current vaccine development and why it takes so much effort, but I want to directly address the question of why we can't just grow some virus, kill it with UV and have a protective vaccine.

The answer is that not all immune responses to viral antigens are helpful in fighting infections of that virus. In some cases it can be harmful; antibodies to dengue virus of one serotype will attach to viral particles of another serotype but aren't able to inactivate them. The attachment of antibodies to active viruses makes their absorption by cells more efficient, and infections where this antibody-dependent enhancement occurs are more severe than first-time dengue infections.

Some viruses have evolved mechanisms to capitalize on this. The reason we need to get a new flu shot every year is that influenza viruses present a "knob" at the end of their glycoprotein that can change its structure and still retain function. This part is much more 'visible' to the immune system than parts of the virus that can't tolerate changes, so the immune response to this variable part outcompetes and prevents an immune response that would provide long-lasting protection. Conserved stalk-targeting vaccines are being intensely investigated for this reason. SARS-CoV-2 may have a immune-faking mechanism as well: the "spike" glycoproteins responsible for binding the ACE2 receptor and entering the cell convert to their post-binding form prematurely part of the time. Antibodies that bind the "post-fusion" form of the protein don't inactivate the virus, and this form sticks out more so may serve to compete for immune attention with the pre-fusion form that would provide protection if bound by antibodies.

In this last example, we can see that a vaccine made of killed SARS-CoV-2 virus particles would be useless if all of the spike proteins had converted to the post-fusion state. The mRNA vaccines therefore don't encode the natural spike protein, but a mutated version which can't convert to the post fusion state as easily:

S-2P is stabilized in its prefusion conformation by two consecutive proline substitutions at amino acid positions 986 and 987

In conclusion, viruses and the immune system are very complicated. Simple vaccines work for some viruses, and don't work for others. When they don't work, the reason is always different, but hopefully I've communicated some general understanding of the background issues.

EDITS: This doesn't relate to the rest of my answer but I want to respond to Ilmari Karonen's and there is not enough room in a comment.

Looking at the timeline for SARS-CoV-2 vaccine development gives a very misleading impression of how long it takes generally. This is because ~90% of the development work was already done before COVID-19 was ever identified, in the 18 years since the SARS-CoV-1 outbreak started in 2002. Vaccines against SARS were developed and tested up to phase I trials, but couldn't proceed further since the virus was eliminated. I discussed this in a previous answer to a similar question, but to expand/reformat, here's some of what we knew and had available on March 17th 2020, when the "covid vaccine timeline" begins:

  1. Identified the receptor as ACE2, and knew that antibodies targeting the receptor binding domain (RBD) of the spike protein neutralize the virus. Protocols to test that these were also true of SARS-CoV-2 were already developed and validated. Without this there would have been a lot more trial-and-error experimentation and false starts with vaccine candidates that looked promising but didn't pan out in testing.
  2. Animal models. There is no naturally-occurring model organism for COVID-19. This is a subtle point because other animals can be infected with the virus, and some develop morbidities because of it. However, these are different enough from what we see in humans that something that protects against the reactions we see in the animal can't be assumed to protect against the reactions that cause problems in humans. For SARS, researchers developed transgenic mice that used the human version of ACE2, and showed that the disease they got from SARS were analogous to the disease humans got. This took several years, and the colony was still available when the virus causing the outbreak in Wuhan was identified as SARS-like and researchers started looking for animal models. As an aside, in an interview on This Week in Virology that I can't find right now, one of the maintainers of that colony said they were months or weeks away from shutting it down and euthanizing all the transgenic mice when the pandemic began, so if funding had been just a bit tighter we probably would not be having this particular conversation now.
  3. How to stabilize the pre-fusion form of coronavirus spike proteins had been determined from work on SARS and MERS vaccines.

In addition to these, a large amount of miscellaneous knowledge about coronavirus functions and the immune reactions to them had been accumulated, and this sped up development, and increased confidence in results, which allows vaccine candidate production and testing to proceed more aggressively.

Historically, vaccine development has taken years or decades of research after the need has been identified. Testing is still longer in many cases, but the current case is very unusual.


While the existing answers are great and cover a lot of the difficulties in vaccine development, I feel that they fail to address (or at least sufficiently emphasize) the fundamental misconception at the core of the question:

If that's the case, why does it take so much time and effort to develop a vaccine, for example, against covid-19?

The answer to that question is simple: developing a vaccine does not take much time. What takes a lot of time is testing the vaccine and making sure that it does not have any unforeseen side effects.

For example, let's take a look at the Pfizer/BioNTech COVID-19 vaccine, since it's been in the news lately. To save time and research effort, I googled for "pfizer covid vaccine timeline" and found this article from Financial Review, whose timeline I will further summarise below:

  • March 17, 2020: Plans to develop the vaccine are announced.
  • April 29, 2020 (six weeks later): First tests on human volunteers begin. At this point the vaccine development is essentially done, and the vaccine has presumably also already passed initial tests using in vitro cell cultures and animal test subjects to ensure that it at least seems to be doing something and doesn't have any obviously bad side effects. (The first human trials are done with four different variants of the vaccine, because the developers obviously want to minimize the risk of having to start over from scratch in case one specific variant turns out to be ineffective or dangerous.)
  • July 1, 2020 (two months later): Preliminary results from the first human tests are announced. One particularly promising candidate vaccine out of the four initial variants is chosen for further testing.
  • December 2, 2020 (five months later): The UK is the first country to approve the vaccine for use through a "rolling review" system, which allows a novel vaccine to be temporarily approved for emergency use in an epidemic even while it still undergoes further testing. Requests for similar emergency use authorizations are currently under review in other countries, including the US and Canada.

So, basically, even under this extremely accelerated emergency testing and approval regime (which squeezed into months what would normally take years), the actual development of the vaccine took less than 20% of the total time from initial planning to approval. All the rest is just testing, testing and more testing.

Now, the other answers have already covered pretty well the reasons why all this testing is needed, but let me anyway give a quick summary for completeness:

  • Vaccines intended for humans need to be tested in humans, because that's the only way to be sure that they work and are safe to use for humans. Cell cultures and animal models can never give a fully accurate picture of how the vaccine will interact with the complete immune system in a real human body.

  • Because all human bodies are different, any new vaccine (or other medical treatment) needs to be tested with as many different people as possible, with as many different ages, ethnic backgrounds, pre-existing conditions, etc. as possible, to make sure that there are no harmful side effects that only show up in a small subset of the population.

  • Also, when testing a vaccine, one of the most important things that need to be confirmed is that it actually prevents the disease. But since it would be grossly unethical to deliberately expose test subjects to a dangerous infection, the only way to test that is to vaccinate a lot of volunteer test subjects and wait for some of them to get naturally exposed to the disease (and then compare the vaccinated test subjects with an unvaccinated control group). This waiting takes time, and since (for most diseases) most of the test subjects will never get exposed and infected anyway, it means that a lot more subjects are needed.

  • Because human testing in inherently risky (but necessary), nobody wants to take the unnecessary risk of administering a completely untested vaccine to a large number of people. But a large number of people still need to be tested to confirm that the vaccine is safe for everyone. Because of this, testing is invariably carried out in multiple phases: first with just a small number of volunteers, then (if no severe issues show up in the initial tests) with a slightly larger group, and then with an even larger group, and so on. But since each new phase can only be started after sufficient data has been collected from the previous phase, this multiplies the already long duration of the testing by several times.

FWIW, most of the same issues apply to all new medical treatments, not just to vaccines. New drug development and testing is also notoriously slow and expensive for pretty much the same reasons - and even then there are plenty of cases where major side effects were only discovered when the drug was already on the market.

One issue that does specifically affect vaccines is that they're preventative treatments that must be administered to a large fraction of the healthy population, not just to already infected people. (Even only vaccinating specific groups at high risk isn't generally sufficient to provide herd immunity.) This means that their safety needs to be tested to a significantly higher standard (since many more people will be receiving the vaccine) and that, as noted above, determining their efficacy requires a must larger pool of test subjects (since not all subjects will be exposed to the disease).

Anyway, the upshot of all this is that if it weren't for all this testing and re-testing, we could've had a COVID-19 vaccine in April, or maybe earlier. (Moderna started their vaccine development already in January, and their first human trials in March.) But even in the face of a global pandemic, the testing is still necessary to make sure that the vaccines that eventually do get approved and widely used will in fact do what they're supposed to do, and that any side effects they may have don't turn out to be worse than the infections they prevent.


BTW, this need for extensive human testing to confirm the safety and effectiveness of a vaccine even after it has been developed is not just the reason why even one company will often develop multiple initial vaccine candidates in parallel, but also one of the main reasons (besides simply capitalism) why there are so many different competing vaccines being developed by different companies. Basically, even the companies that were late to start their vaccine development and testing could, for a long time, still hope to be the first ones to market if testing happened to turn up serious issues with their competitors' vaccines.

Of course, other reasons exist too: the second, third, fourth etc. companies to get their vaccine approved can also expect to win a decent share of the market, especially if their vaccine happens to be cheaper, more effective and/or easier to store and transport than the alternatives. Also, many countries may prefer to use a locally developed and produced vaccine if one is available in order to limit their dependence on foreign suppliers.


While it is true that deactivated (e.g. heat killed viruses) are used in some cases, the Pfizer, Moderna vaccines are in fact mRNA vaccines. The figure below from the Oxford website details the processes involved in vaccine their DNA based vaccine development. This Moderna page has a video detailing their approach as well. Pfizer also has a nice video explaining the process of mRNA vaccine development.
As you can see, it is not an easy process. A prerequisite of both their solutions is the knowledge of the SARS-CoV-2 genome sequence (in this case the genome is a single stranded RNA). This requires some time to get done and once the data is available, one has to wait for others to verify it to some extent. Interestingly, the Moderna video says that they had a human ready vaccine in 42 days.

The differences in efficiency can stem from multiple factors:

  1. What vector is used to deliver the vaccine
  2. How the mRNA is tweaked to produce Spike glycoprotein
  3. Physiology of the individuals receiving the vaccine

and many other factors which are beyond the scope of a single answer and can be proprietary knowledge of the manufacturers.

Another significant addition to the 'time' factor is the clinical trials. Pfizer and Moderna require two doses spaced over 3-4 weeks for their phase-I trials. Since these vaccines are being rapidly developed, and you are amidst a global pandemic, you get only 1 chance at a clinical trial (and subsequent profits) and you have to make it count. Various national regulatory authorities also need to keep the health of their citizens in mind. Thus there is immense pressure to get these trials done right and the global consensus in this case seems to be taking a slightly long duration of clinical testing.

Regarding the last question, no, none of the Oxford, Pfizer or Moderna vaccines care about damage done to the original pathogen because there is no pathogen being delivered.


Why a Vaccine Can Provide Better Immunity than an Actual Infection

Vaccines have advantages over natural infections. For one, they can be designed to focus the immune system against specific antigens that elicit better responses.

Two recent studies have confirmed that people previously infected with SARS-CoV-2, the virus that causes COVID-19, can be reinfected with the virus. Interestingly, the two people had different outcomes. The person in Hong Kong showed no symptoms on the second infection, while the case from Reno, Nevada, had more severe disease the second time around. It is therefore unclear if an immune response to SARS-CoV-2 will protect against subsequent reinfection.

Does this mean a vaccine will also fail to protect against the virus? Certainly not. First, it is still unclear how common these reinfections are. More importantly, a fading immune response to natural infection, as seen in the Nevada patient, does not mean we cannot develop a successful, protective vaccine.

Any infection initially activates a non-specific innate immune response, in which white blood cells trigger inflammation. This may be enough to clear the virus. But in more prolonged infections, the adaptive immune system is activated. Here, T and B cells recognise distinct structures (or antigens) derived from the virus. T cells can detect and kill infected cells, while B cells produce antibodies that neutralise the virus.

During a primary infection – that is, the first time a person is infected with a particular virus – this adaptive immune response is delayed. It takes a few days before immune cells that recognise the specific pathogen are activated and expanded to control the infection.

Some of these T and B cells, called memory cells, persist long after the infection is resolved. It is these memory cells that are crucial for long-term protection. In a subsequent infection by the same virus, the memory cells get activated rapidly and induce a robust and specific response to block the infection.

A vaccine mimics this primary infection, providing antigens that prime the adaptive immune system and generating memory cells that can be activated rapidly in the event of a real infection. However, as the antigens in the vaccine are derived from weakened or noninfectious material from the virus, there is little risk of severe infection.

A better immune response

Vaccines have other advantages over natural infections. For one, they can be designed to focus the immune system against specific antigens that elicit better responses.

For instance, the human papillomavirus (HPV) vaccine elicits a stronger immune response than infection by the virus itself. One reason for this is that the vaccine contains high concentrations of a viral coat protein, more than what would occur in a natural infection. This triggers strongly neutralising antibodies, making the vaccine very effective at preventing infection.

The natural immunity against HPV is especially weak, as the virus uses various tactics to evade the host immune system. Many viruses, including HPV, have proteins that block the immune response or simply lie low to avoid detection. Indeed, a vaccine that provides accessible antigens in the absence of these other proteins may allow us to control the response in a way that a natural infection does not.

The immunogenicity of a vaccine – that is, how effective it is at producing an immune response – can also be fine tuned. Agents called adjuvants typically kick-start the immune response and can enhance vaccine immunogenicity.

Alongside this, the dose and route of administration can be controlled to encourage appropriate immune responses in the right places. Traditionally, vaccines are administered by injection into the muscle, even for respiratory viruses such as measles. In this case, the vaccine generates such a strong response that antibodies and immune cells reach the mucosal surfaces in the nose.

However, the success of the oral polio vaccine in reducing infection and transmission of polio has been attributed to a localised immune response in the gut, where poliovirus replicates. Similarly, delivering the coronavirus vaccine directly to the nose may contribute to a stronger mucosal immunity in the nose and lungs, offering protection at the site of entry.

Understanding natural immunity is key

A good vaccine that improves upon natural immunity requires us to first understand our natural immune response to the virus. So far, neutralising antibodies against SARS-CoV-2 have been detected up to four months after infection.

Previous studies have suggested that antibodies against related coronaviruses typically last for a couple of years. However, declining antibody levels do not always translate to weakening immune responses. And more promisingly, a recent study found that memory T cells triggered responses against the coronavirus that causes Sars almost two decades after the people were infected.

Of the roughly 320 vaccines being developed against COVID-19, one that favours a strong T cell response may be the key to long-lasting immunity.

This article is republished from The Conversation under a Creative Commons license. Read the original article.


MYTH: If I’ve already had COVID-19, I don’t need a vaccine.

FACT: People who have gotten sick with COVID-19 may still benefit from getting vaccinated. Due to the severe health risks associated with COVID-19 and the fact that re-infection with COVID-19 is possible, people may be advised to get a COVID-19 vaccine even if they have been sick with COVID-19 before.

There is not enough information currently available to say if or for how long people are protected from getting COVID-19 after they have had it (natural immunity). Early evidence suggests natural immunity from COVID-19 may not last very long, but more studies are needed to better understand this. Several subjects in the Pfizer trial who were previously infected got vaccinated without ill effects. Some scientists believe the vaccine offers better protection for coronavirus than natural infection.


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SINGAPORE: Over 70 teams worldwide are now in a collaborative race to test different vaccine candidates against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes COVID-19.

Although the pace of research efforts has been extraordinary, scientists still estimate that producing a vaccine, from innovation to access, will take at least 12 to 18 months. This timeline has the caveat “if all goes well”.

To the public, this seems like a long wait. But most vaccinologists who study and develop vaccines view this as very optimistic. It normally takes more than 10 years for a vaccine candidate to become an approved vaccine in a public immunisation programme.

Vaccine development is complex and financially risky. A vaccine candidate can fail at any point in development. Having a few candidates do well in clinical trials is considered a best-case scenario.

It is important to understand that all we have currently are experimental vaccine candidates not ready to be used soon. A vaccine candidate is not a confirmed human vaccine.

It must undergo ethical reviews, be evaluated in animal studies, for safety and efficacy in clinical trials involving human volunteers, before receiving regulatory approval and licensing for marketing and widespread use.

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Vaccine manufacturing plants must be pre-inspected and approved for sterile manufacturing conditions, quality controls, and production ramped up to support potentially billions of vaccine doses.

Public health policies and financing decisions for national public programmes need to be in place. Follow-up studies must be set up to closely monitor the vaccine’s long-term safety and effectiveness with large-scale immunisation.

This is even more important for an accelerated vaccine using new technology against a new virus.

ACCELERATING IN PARALLEL

For the COVID-19 pandemic, scientists, regulators, government and industry leaders have been working closely to accelerate coordination of the different requirements to run at parallel speed with some vaccine candidates which have already entered clinical trials.

An Israeli scientist works at a laboratory at the MIGAL Research Institute in Kiryat Shmona in the upper Galilee in northern Israel where efforts are underway to produce a vaccine against the coronavirus. (JALAA MAREY/AFP)

INTERACTIVE: All the COVID-19 clusters at dorms and construction sites

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In addition to the World Health Organization’s guiding role, the Coalition for Epidemic Preparedness Innovations was established in 2017 by the Wellcome Trust, the Bill & Melinda Gates Foundation and several governments, and has invested in several projects to help speed up the development of COVID-19 vaccines.

Timelines for animal and human trial studies are being compressed, but always carefully weighing potential risks.

For vaccine candidates developed using more well-known and evaluated technologies, some clinical studies in human volunteers have started earlier and overlapped with animal studies usually carried out before human studies. However, some areas cannot be shortened or accelerated, such as collecting ongoing safety data on side effects.

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Regulatory reviews are being sped up. Instead of requiring submission of all information from completed clinical trials, regulatory agencies are now open to receiving data on an ongoing rolling basis.

To save on time needed for analysis and discussion, “chapters” of clinical trial data can be submitted for review in real-time, rather than wait until the end to submit the usual complete “book” of data when all trials are finished.

Each vaccine has its own benefits and risks profile. Regulators must be updated and agile to manage risk tolerance and potential benefits of these urgently needed new technologies.

Manufacturing plans are also being accelerated in some countries. Plans in the US are already underway to scale up manufacturing to produce massive amounts of certain vaccine candidates.

Bill Gates has publicly supported developing manufacturing capacity for some vaccine candidates just starting clinical trials, fully aware not all candidates will cross the finish line.

Such early production, with quality checks done in advance, can shave off weeks to months for manufacturing billions of vaccine doses needed to reduce the ongoing human and economic toll.

READ: Commentary: COVID-19 collapse exceeds any recession in the last 150 years

FILE PHOTO: A man and a child wear protective masks, looking at empty shelves of canned food and instant noodles as people stock up on food supplies, after Singapore raised coronavirus outbreak alert level to orange. (REUTERS/Edgar Su)

Several questions are emerging surrounding financing and equitable distribution of any vaccines that get developed. What will it cost? Will the vaccine be considered a common good for all people? Will the technology be shared? Which countries and which population groups are prioritised to gain access first?

This last question is a concern if countries with ongoing spread are unable to afford a vaccination programme. Strong leadership, global governance and a collective commitment to social justice will be needed.

HOW VACCINES WORK

All vaccines work using the same principles. A healthy person (the vaccinee) is given a piece of the germ or the germ itself in order to give a “heads up” to his or her immune system, so that it can later recognise and tackle the virus appropriately.

If the person gets exposed to the real virus later, his or her immune memory will activate earlier to kill the virus and block its spread. The vaccinee stays healthy, often unaware of being exposed to the threat.

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Choosing the best “picture” (antigens) of the SARS-CoV-2 virus to show to our immune systems, in order to stimulate the right immune memory and appropriate antibodies, is where the challenge really lies for scientists.

A good, safe and effective SARS-CoV-2 vaccine must accurately capture the important features of this virus in order to generate the best immune memory. Ideally, a vaccine would show the immune system the entire process of SARS-CoV-2 infection so that it can develop ways to attack the virus at different fronts.

But it is challenging to genetically weaken SARS-CoV-2 such that it would cause infection but not the disease itself.

Most vaccine researchers have thus turned to technologies that can present different pictures, or pieces, of SARS-CoV-2 to our immune systems.

Dozens of pharmaceuticals and research labs across the world are racing to develop a vaccine. (Photo: AFP/Thibault Savary)

Much research has been focused on the spike proteins forming the “crown” or “corona” of SARS-CoV-2. This appears crucial in how the virus attaches to and infects human cells.

We are beginning to learn that the spike protein is liberally “decorated” with sugars. Displaying the right sugars on vaccines appears important to show the immune system the correct “picture”.

Some vaccine candidates in the running present the genetic code (RNA or DNA) of the spike protein. Our cells then translate the genetic code to make the spike protein in the body.

Another method is to insert SARS CoV-2 genes into a safe, licensed viral vaccine to deliver the piece of SARS CoV-2 using a well-known, harmless virus.

We might not be able to develop a vaccine that provides the perfect picture of the virus to vaccinees. But even a partially effective, safe vaccine could be very valuable. The vaccine may not stop all cases or symptoms but could prevent severe respiratory distress and deaths.

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When many people become immune – either through vaccination or surviving the infection - the virus cannot infect enough susceptible people to propagate. This population “herd immunity” is needed to end an epidemic or prevent one from gaining traction.

THE NEED FOR DIVERSITY AND SOME LUCK

While there are many ways to make vaccine candidates, we do not yet know how to pick winners. Furthermore, scientists still have much to learn about how this new virus behaves.

There remains an element of luck when looking for a good vaccine against a new virus we are only getting to know. But our chances have improved with the unprecedented number of vaccine candidates being developed and with the scientific world so focussed on COVID-19.

The huge human, social and economic fallout from this pandemic means we should leave no stone unturned and invest heavily in a wide range of vaccine candidates to find good, safe and effective vaccines.

The head of a major Russian research centre said scientists at a top-secret lab complex located in Koltsovo outside the Siberian city of Novosibirsk has developed several prototype coronavirus vaccines. (photo: AFP/Alexander NEMENOV)

Many SARS-CoV-2 vaccine candidates are exploring using new technologies. To help shorten clinical trial duration and reduce the number of human volunteers, some research groups are studying the use of molecular technologies to complement clinical trials.

There is also hope that the similar explosion of studies for safe, effective medicines to treat COVID-19, including anti-viral medicines and potential antibody treatments, will yield positive results. These are likely to arrive much sooner than a vaccine.

The unfortunate surge of clinical experience in managing severe respiratory distress with COVID-19 could also lead to other best practices to improve patient outcomes where capacity is available.

MEANWHILE, CARRY ON

A COVID-19 vaccine will unfortunately not be available this year. If all goes well, a vaccine or even a few vaccines will be rolled out in 2021.

For now, other public health measures are essential to save lives, including early case detection, contact tracing, isolation and quarantine.

We must practise frequent hand washing, physical distancing, staying at home, avoiding crowded places, and wearing face masks if we really need to go out.

COVID-19 is testing our collective scientific ingenuity, our individual responsibilities and social compact at a national and global level.

We must stay committed to our individual contributions and believe in our collaborative power in science to help develop and deliver long-term solutions.

BOOKMARK THIS: Our comprehensive coverage of the coronavirus outbreak and its developments

Download our app or subscribe to our Telegram channel for the latest updates on the coronavirus outbreak: https://cna.asia/telegram

Dr Tippi Mak is Academic Visiting Expert at the Centre of Regulatory Excellence, Duke-NUS Medical School, Consultant at the SingHealth Duke-NUS Global Health Institute, and Board Director of the Vaccine and Infectious Disease Organization - International Vaccine Centre at the University of Saskatchewan, Canada.

Professor Ooi Eng Eong is Deputy Director at the Emerging Infectious Diseases Programme, Duke-NUS Medical School and Co-Director at the Viral Research and Experimental Medicine [email protected] Duke-NUS.

Professor John CW Lim is Executive Director at the Centre of Regulatory Excellence, Duke-NUS Medical School, Policy Core Lead at the SingHealth Duke-NUS Global Health Institute, and Chairman of the Singapore Clinical Research Institute & National Health Innovation Centre.


Why will it take so long to develop a COVID-19 vaccine?

This article was published more than 1 year ago. Some information in it may no longer be current.

A participant in a COVID-19 vaccine trial receives an injection in Kansas City, Mo., on April 8, 2020.

Question: I’ve read that it could be one to two years before we have a vaccine that will guard against COVID-19. Why is it going to take so long?

Answer: The development of any vaccine can be compared to a long and challenging marathon with an uncertain outcome – and that is especially true when dealing with a new pathogen.

The purpose of a vaccine is to expose the body’s immune system to some portion of the virus so it can prepare in advance for a real attack. For instance, a vaccine might include an antigen, or protein, from the surface of the virus. But finding the antigen that will trigger an effective immune response is easier said than done.

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“Science cannot be rushed,” says Rob Kozak, a clinical microbiologist at Sunnybrook Health Sciences Centre in Toronto. Researchers must follow well-established regulatory protocols that are designed to ensure a therapy is both effective and safe.

Viruses are constantly mutating and evolving. The strain of a virus circulating in Canada might be slightly different from the one in China or Europe. This means the antigen must produce immunity against all strains, or variants, of the virus.

Once an antigen is selected, it has to be tested in animals before human trials can begin. Finding the appropriate animal model also presents challenges. The animal needs to respond to the virus – and the vaccine – in the same way as people.

Fortunately, researchers can look to previous vaccine studies for clues on how to respond to the current pandemic, including selecting appropriate animal models and viral targets.

The COVID-19 illness is caused by a coronavirus, officially known as SARS-CoV-2. In recent years, humanity has been challenged by two other deadly coronaviruses – Severe Acute Respiratory Syndrome (SARS) in 2003 and Middle East Respiratory Syndrome (MERS) in 2012. During both of these outbreaks, researchers started to develop vaccines. In the case of SARS, the work was never completed partly because the virus ceased to pose an immediate threat it seems to have morphed and disappeared. MERS vaccine trials are continuing.

Previous SARS research reinforces the importance of doing thorough testing in animal models before any potential vaccine is given to human volunteers.

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In one study, an experimental SARS vaccine made lab animals worse, says Arinjay Banerjee, an emerging-viruses researcher at McMaster University in Hamilton.

“This study showed that when mice were vaccinated and then challenged with the pathogen, there was an enhancement of the infection,” he says. “The vaccinated mice developed disease more rapidly and died more rapidly than the unvaccinated mice.”

Another study revealed that some investigational SARS vaccines produced negative side effects in some types of animals (such as ferrets) but not in others (such as mice). For that reason, many researchers are convinced that a vaccine should be tested in two different types of animals, Kozak says.

All this preclinical work is time consuming. Laboratory animals require specific time periods to develop a response to the vaccine and then to react to the virus. The clock cannot be made to run faster, Kozak says. And if an experimental vaccine fails, a research team could find itself again at the starting gate.

After a vaccine has successfully passed animal testing, it is then tried in a small group of healthy volunteers. This is known as a phase-one clinical trial. It’s basically a safety check to make sure the vaccine does not cause serious side effects.

If the vaccine clears this critical hurdle, trials are expanded gradually to include more people who are observed for longer periods of time in order to gain a better understanding of its risks and benefits.

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Scientists around the world are already exploring various ways to deliver a COVID-19 vaccine. “Each of them have their advantages and disadvantages,” Kozak says.

“To be honest, I don’t think we are going to have just one vaccine,” he adds. “In fact, I hope we don’t. I hope we have three or four amazing candidates that all work basically as well as each other, and that could be critically important because you don’t want to be dependent on only one company to provide for the world.”

Like other experts, Dr. Kozak estimates it will take between one to two years to develop a vaccine. And once a vaccine does exist, special production facilities will have to gear up operations to meet the global demand. That, too, will take time.

All of which means that a “quick fix” vaccine is not on the immediate horizon.

Paul Taylor is a Patient Navigation Adviser at Sunnybrook Health Sciences Centre. He is a former Health Editor of The Globe and Mail. Find him on Twitter @epaultaylor and online at Sunnybrook’s Your Health Matters.

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The Children's Vaccine Initiative: Achieving the Vision (1993)

For the purposes of this chapter, the process of vaccine research and development (R&D) is described as if the process occurs in an ordered, chronological fashion. In this somewhat simplified view, vaccine research begins only after a careful assessment of public health priorities. Work conducted in the basic research laboratory forms the scientific foundation for all subsequent investigation. Applied R&D then moves to the clinical research setting, and from there to pilot production and full-scale manufacture. The vaccine must then be purchased, distributed, and used. Finally, a surveillance system is established to monitor immunization coverage, efficacy, and any adverse health effects related to vaccine administration. The surveillance system also may detect fluctuations in disease incidence or new disease entities requiring a realignment of public health priorities.

In reality, the stages of vaccine development are not so neatly divided. For instance, although basic research is the starting point, it does not end when applied R&D begins basic research findings continue to inform the process of vaccine development, even during clinical testing. Likewise, findings at the applied and clinical levels feed observations and questions back to the basic research laboratory.

In Chapter 5, the committee examined broad questions of market potential and technical feasibility, both of which influence the decision to invest in the development of new or improved vaccines. After this decision to invest in a vaccine is taken, vaccine manufacturers are then frequently faced with a range of impediments as a product moves through the

successive steps of development.

This chapter describes the various phases of vaccine development and a number of obstacles that can arise in this process. These barriers can discourage initial investment or prevent the vaccine from advancing beyond a certain stage. At every step, commercial manufacturers weigh the likelihood of product success against its market potential.

PRIORITY SETTING

The decision-making process for the development and production of vaccines should be guided by an assessment of critical public health needs. Priorities should be established and the desired vaccine characteristics should be defined. In this way, the vast resources of the U.S. and international public and private sectors can be directed to a set of common and complementary goals.

There have been major efforts over the past decade to establish priorities for vaccine development (Institute of Medicine, 1986a,b National Institute of Allergy and Infectious Diseases, 1992a,b World Health Organization, 1991 World Health Organization/Children's Vaccine Initiative, 1992c). As discussed in Chapter 3, much of the basic vaccine research conducted by the National Institute of Allergy and Infectious Diseases (NIAID) targets the development of priority vaccine candidates identified in 1986 by the Institute of Medicine (Institute of Medicine, 1986a,b National Institute of Allergy and Infectious Diseases, 1992a,b), and much progress has been made (National Institute of Allergy and Infectious Disease, 1992b).

At present, new efforts are under way to develop priorities for vaccine R&D. The Task Force on Priority Setting and Strategic Plans of the World Health Organization's (WHO's) Children's Vaccine Initiative (CVI) recently completed a major cost-effectiveness assessment of vaccine-development priorities, and the WHO/United Nations Development Program's (UNDP) Program for Vaccine Development maintains a list of priority areas for vaccine development. In addition, the World Bank, as part of the World Development Report of 1993, Investing in Health (World Bank, 1993), is using Disability Adjusted Life Years to estimate the burden of disease and priorities for intervention.

Whatever priorities are set by the public sector, the ultimate decision to develop and manufacture a vaccine for general use in the United States rests entirely with the commercial vaccine manufacturers (see Chapters 3, 4 and 5 and Appendix H). Commercial manufacturers vigorously pursue the development of those products with market potential (see Chapter 4). Vaccines used exclusively in the developing world hold little promise of

significant returns on investment, and companies are reluctant to invest in developing such high-risk and commercially unattractive products (see Chapter 5).

The committee believes that priority setting and characterization of desired vaccine products is a critical stage of vaccine development, particularly for vaccines of low commercial interest but acute public health need. In this regard, the committee urges all groups involved in vaccine R&D for international public health applications to focus on a common and complementary set of vaccine priorities.

BASIC AND APPLIED RESEARCH

The fundamental scientific advances that make vaccine development possible arise from basic research. The full implications and ultimate applications of discoveries made in the basic research laboratory may be unanticipated, even by the investigators involved. Basic research relevant to vaccine development includes such things as the identification and isolation of the protective antigens of a specific pathogen, methods for DNA cloning, the creation of new vector systems, and the development and immunologic evaluation of new adjuvant systems.

Basic research is conducted primarily by federally funded academic and government scientists. Once a basic scientific finding is thought to have significant and practical applications, the research moves on to applied R&D (the exploratory development phase). Much applied research and almost all product-development activity are conducted by private industry. Both biotechnology firms and vaccine manufacturers invest in developing new technologies to deliver and enhance the quality and efficacy of vaccines. Unfortunately, some CVI-specific vaccine technologies (e.g., heat stabilization of viral vaccines) are unlikely to be pursued by U.S. firms, because such technologies would have little comparative advantage in the domestic market. The committee believes that additional incentives can be provided to university-based researchers, commercial vaccine manufacturers, and biotechnology companies to stimulate the development of such technologies and their subsequent handoff from basic research to the product-development stages. Possible incentives are discussed in Chapter 7.

CLINICAL EVALUATION

Good vaccines must meet basic criteria of safety, purity, potency, and efficacy. When a product has completed preclinical studies (usually

involving animal models) and the sponsor is considering clinical trials in humans, an Investigational New Drug (IND) application is submitted to the U.S. Food and Drug Administration (FDA). The IND application contains information on the vaccine's safety, purity, potency, and efficacy (see Appendix C). These parameters are then evaluated in clinical trials, which are usually carried out in four phases (Table 6-1). Phase I trials are short-term studies involving a small number of subjects and are designed primarily to evaluate the safety of the candidate vaccine, its ability to induce an immune response (immunogenicity), the optimal dose range, and the preferred route of administration to achieve the most effective immune response. Studies are usually conducted in individuals at low risk of acquiring natural infection in order to avoid confusing results.

Following the successful completion of phase I trials, phase II trials are conducted these may involve up to hundreds of subjects. Phase II trials are usually double-blind studies with a placebo-control group phase II trials expand the evaluation of the safety and immunogenicity of the vaccine and may include the responses of individuals at risk of acquiring the infection. For a treatable pathogen, trials can be conducted in susceptible adults under controlled conditions to assess the ability of the vaccine to confer protection against experimental challenge. The results of these pilot studies can provide the information necessary to proceed with phase III studies.

Phase III trials are usually conducted in a double- or single-blind, placebo-controlled, randomized manner and in hundreds to thousands of individuals at risk for acquiring the infection or disease. Because of the lengthy observation period that may be required, the longer-term safety of the vaccine can also be assessed in a large number of subjects. Such trials are expensive, require a well-developed health infrastructure and large study groups (sometimes in non-U.S. populations), and, as with all stages of clinical investigation, demand experienced personnel and laboratory capacity for surveillance. Additional expenses are incurred if testing of live attenuated or live recombinant vaccines requires isolation facilities for phase I and II trials. Study design, data collection, and analysis are all of critical importance for ensuring the quality of trial results for licensing a candidate vaccine.

Phase IV trials may be conducted after a product is licensed, as part of postmarketing surveillance. They provide information about the safety and effectiveness of the vaccine in the general population, usually under normal (nonstudy) conditions.

Clinical trials are time-consuming (sometimes taking years), complex, and costly. Clinical trials for CVI vaccines, which are targeted for infants and young children, will be more challenging and time-consuming than those for vaccines designed for adults and older children. The safety and immunogenicity of many CVI vaccines will need to be demonstrated in trials


A key consideration is funding – public and private cash has been poured into the race for a Covid vaccine, pushing aside the usual financial concerns facing pharmaceutical companies. What’s more, demand and urgency are high.

“The fact that governments pre-bought the vaccines meant that people could take greater risks with what they did at an earlier stage without having to take one step at a time,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine.

Traditionally, vaccines are developed by weakening it or killing a virus, or by producing part of the virus in the lab. However this is time consuming.

Instead, both the Oxford University/AstraZeneca and Pfizer/BioNTech vaccines were developed using different “platform technologies” that involve slotting genetic material from the virus into a tried and tested delivery package. Once introduced into the human body this genetic material is used by the protein-making machinery in our cells to churn out the coronavirus “spike protein”, triggering an immune response.

This approach was aided by the speed at which scientists in China identified and shared the genetic sequence of the new coronavirus, and work that was already under way on other coronaviruses.

But while such platform technologies are a non-traditional approach, that does not mean they are untested.

“The mRNA vaccine platform technology [which the Pfizer/BioNTech vaccine uses] has been in development for over two decades,” said Dr Zoltán Kis, of Imperial College London.

The use of platform technologies not only means a vaccine can be rapidly developed, and that more is known about its safety profile from the start, but production is faster and cheaper as existing production processes can be used.

Another consideration is that while in traditional vaccine development the phases of clinical trials are carried out in sequence, in the case of the Covid vaccines they have overlapped, making the process faster.

“Vaccine manufacturing has also been carried out in parallel with the clinical trials, hoping that trials will succeed,” said Kis.

Evans added that the large trial sizes and duration was reassuring. “I have seen no corners that have been cut,” he said.

Finally, advances in tech have streamlined data-recording, while the advent of social media has made it easier to recruit trial participants – something aided by a strong public desire to help.

“It normally takes weeks or months to recruit to a study. This one, it kind of happened overnight,” said Prof Adam Finn, a vaccine expert at the University of Bristol and an investigator on the Oxford/AstraZeneca trials.


Vaccine Q&A: How Long Does It Take to Make Vaccines?

In this post, we focus on how long it takes to develop and manufacture vaccines – particularly those designed to protect against COVID-19.

To address those questions, we spoke with Jennifer Pancorbo, director of industry programs and research at NC State’s Biomanufacturing Training and Education Center. Pancorbo is an expert in vaccine manufacturing, with particular expertise in viral vector vaccine development and production processes.

This post is part of a series of Q&As in which NC State experts address questions about the vaccines on issues ranging from safety to manufacturing to how the vaccines will be distributed.

The Abstract: How long does it take to make vaccines?

Jennifer Pancorbo: There are two ways to interpret this question. Do you mean actually manufacturing a vaccine that is already created? Or do you mean designing a new vaccine?

Developing a new vaccine from scratch takes considerable time. It depends a lot on how much information is available about the disease itself, how the disease infects people and spreads, and so on. But it traditionally has taken 5-10 years to get a new vaccine. That makes it truly amazing that we already have one authorized vaccine for COVID-19, and are evaluating stage 3 clinical trial data on others. It speaks volumes about the efforts put into pandemic preparedness and response.

As for actual manufacturing time, that can be affected by the type of vaccine being made – though this isn’t really relevant for COVID-19, since all of the vaccines being considered for COVID-19 take about the same amount of time to manufacture.

If we are talking about a vaccine that has already been tested and approved, we could generalize and say that one batch of vaccine, consisting of a couple thousand doses, may take 2-6 weeks to go from starting with raw materials to being a completed vaccine in a vial or syringe.

TA: What types of vaccines are the most promising COVID-19 vaccine candidates?

Pancorbo: mRNA and adenovirus vaccines seem to be the most promising candidates at this time. Those two production systems lend themselves well to rapid design and that is probably why those candidates are coming out first.

We may or may not see a candidate vaccine made with a more traditional technology in the future. It is hard to tell, and may depend a lot on how the initial vaccines work and how much room is left in the market for a different candidate.

TA: How long does it take to make conventional vaccines? And why does it take so long?

Pancorbo: Again there are two angles here.

First, from the stand point of design, it takes a while to understand the disease, its path of infection and spread, in order to find a way to stop it. Also, once an idea to alert the immune system of the invader is conceived, then you need to test the candidate to make sure the conceptual idea works. Once that is acceptable, then you need to establish a manufacturing process that lends itself to large scale production… all those steps take time.

Second, from the stand point of manufacturing, most vaccines are biologicals – meaning they are produced with help from a microorganism. And that means you need time for the microorganisms to grow and get the job done. Here’s a general overview of the process:

Scanning electron microscopy image of SARS-CoV-2. Image credit: National Institute of Allergy and Infectious Diseases-Rocky Mountain Laboratories, NIH

To produce a vaccine using a biological system, you first select a suitable host. This is typically a well-known organism like bacteria or yeast. Then the genetic material of the host is engineered to provide instructions for the expression of the desired vaccine. In other words, you engineer the organism to make the vaccine for you. The newly engineered organism is then grown in sufficient quantities to be used for production purposes. Once expression is completed by the organism, our vaccine is separated from everything else the organisms produce using operations like filtration. The last step is to mix the purified vaccine with the excipients –or those other components that add stability to the vaccine and allow us to safely transport and store it. The formulated vaccine is then filled into multi-dose vials or single-use syringes for administration.

And there is one more thing, once all the above is completed, then each batch produced must be tested for identity, purity and potency to make sure everyone receives a quality product. As you can imagine, all that takes weeks per batch.

TA: And how long does it take to make mRNA vaccines?

Pancorbo: I am not sure anyone knows this accurately at this point, since no mRNA vaccine has been manufactured before at any scale close to what will be required for COVID-19. I am going to dare say that it will take at least a couple of weeks per batch.

[Editor’s note: Pancorbo followed up with us after this post was first published to offer some additional insight into the manufacturing process for mRNA vaccines, including the Pfizer and Moderna vaccines. We’ve inserted that information as the following paragraph.]

These vaccines, both Pfizer and Moderna’s, start with making a template. (The template itself is made with help from an organism and needs to be purified prior to use.) The template is then used to create the naked mRNA that constitutes the main vaccine ingredient. The naked mRNA is purified and packed into small spheres made of very specific types of fat. These spheres are called liposomes, and they are then formulated, filled into multi-dose vials and made ready for distribution.

TA: What about adenovirus vaccines?

Pancorbo: Again, we don’t have an adenovirus vaccine in the market, so my response is the same as what I said about mRNA vaccines.

TA: How long will it take manufacturers to scale up production once a vaccine has been approved by the FDA?

Pancorbo: Most of the companies you hear about on TV have already started doing this “at risk,” so they can manage demand.

Once you find a device that works you cannot really go to your local grocery store to get one.

At-risk manufacturing means you don’t have approval, or you don’t know if the vaccine is going to work, but to reduce or eliminate waiting time to get to the market, you move forward with scale up, construction, manufacturing, etc. The risk is that the investment will not be returned if the vaccine is ineffective or if it is not approved.

It may take several years to scale up a production process like this to the levels required for COVID-19. It involves testing production in a larger vessel. Testing the purification equipment in a larger footprint – and this may get tricky as making soup for four people is not the same as making soup for 100 people. Another bottleneck is equipment and raw material availability. Once you find a device that works you cannot really go to your local grocery store to get one. The same is true for the basic raw materials and supplies – both need time to react to the larger demand.

TA: How much vaccine manufacturing takes place in the U.S.? Do we rely on importing vaccines, or do we have the capacity to make our own?

Pancorbo: Not much vaccine manufacturing takes place in the U.S., really. Traditionally, vaccines were manufactured in other places around the world. After the 2009 flu pandemic our government put a considerable investment into increasing vaccine manufacturing in the U.S., but the larger manufacturers – like Sanofi – are headquartered outside our borders.

TA: How long do you think it will take manufacturers to make enough vaccine to reach everyone who can be vaccinated?

Pancorbo: I would think it will take until late 2021 or mid-2022 to see a significant amount of the population vaccinated.

TA: Will you get the vaccine once it’s available?

Pancorbo: Yes. The approval process followed by FDA is very thorough and trustworthy. And, particularly for COVID-19, a lot of information about the vaccine candidates has been made public from early on, which gives me an additional confidence in the process.


How will vaccine recipients be informed about the benefits and risks of any vaccine that receives an EUA?

FDA must ensure that recipients of the vaccine under an EUA are informed, to the extent practicable given the applicable circumstances, that FDA has authorized the emergency use of the vaccine, of the known and potential benefits and risks, the extent to which such benefits and risks are unknown, that they have the option to accept or refuse the vaccine, and of any available alternatives to the product. Typically, this information is communicated in a patient “fact sheet.” The FDA posts these fact sheets on our website.


How long does it take to make vaccines?

Scanning electron microscopy image of SARS-CoV-2. Credit: National Institute of Allergy and Infectious Diseases-Rocky Mountain Laboratories, NIH

In this post, we focus on how long it takes to develop and manufacture vaccines—particularly those designed to protect against COVID-19.

To address those questions, we spoke with Jennifer Pancorbo, director of industry programs and research at NC State's Biomanufacturing Training and Education Center. Pancorbo is an expert in vaccine manufacturing, with particular expertise in viral vector vaccine development and production processes.

This post is part of a series of Q&As in which NC State experts address questions about the vaccines on issues ranging from safety to manufacturing to how the vaccines will be distributed.

The Abstract: How long does it take to make vaccines?

Jennifer Pancorbo: There are two ways to interpret this question. Do you mean actually manufacturing a vaccine that is already created? Or do you mean designing a new vaccine?

Developing a new vaccine from scratch takes considerable time. It depends a lot on how much information is available about the disease itself, how the disease infects people and spreads, and so on. But it traditionally has taken 5-10 years to get a new vaccine. That makes it truly amazing that we already have one authorized vaccine for COVID-19, and are evaluating stage 3 clinical trial data on others. It speaks volumes about the efforts put into pandemic preparedness and response.

As for actual manufacturing time, that can be affected by the type of vaccine being made—though this isn't really relevant for COVID-19, since all of the vaccines being considered for COVID-19 take about the same amount of time to manufacture.

If we are talking about a vaccine that has already been tested and approved, we could generalize and say that one batch of vaccine, consisting of a couple thousand doses, may take 2-6 weeks to go from starting with raw materials to being a completed vaccine in a vial or syringe.

TA: What types of vaccines are the most promising COVID-19 vaccine candidates?

Pancorbo: mRNA and adenovirus vaccines seem to be the most promising candidates at this time. Those two production systems lend themselves well to rapid design and that is probably why those candidates are coming out first.

We may or may not see a candidate vaccine made with a more traditional technology in the future. It is hard to tell, and may depend a lot on how the initial vaccines work and how much room is left in the market for a different candidate.

TA: How long does it take to make conventional vaccines? And why does it take so long?

Pancorbo: Again there are two angles here.

First, from the stand point of design, it takes a while to understand the disease, its path of infection and spread, in order to find a way to stop it. Also, once an idea to alert the immune system of the invader is conceived, then you need to test the candidate to make sure the conceptual idea works. Once that is acceptable, then you need to establish a manufacturing process that lends itself to large scale production… all those steps take time.

Second, from the stand point of manufacturing, most vaccines are biologicals—meaning they are produced with help from a microorganism. And that means you need time for the microorganisms to grow and get the job done. Here's a general overview of the process:

To produce a vaccine using a biological system, you first select a suitable host. This is typically a well-known organism like bacteria or yeast. Then the genetic material of the host is engineered to provide instructions for the expression of the desired vaccine. In other words, you engineer the organism to make the vaccine for you. The newly engineered organism is then grown in sufficient quantities to be used for production purposes. Once expression is completed by the organism, our vaccine is separated from everything else the organisms produce using operations like filtration. The last step is to mix the purified vaccine with the excipients –or those other components that add stability to the vaccine and allow us to safely transport and store it. The formulated vaccine is then filled into multi-dose vials or single-use syringes for administration.

And there is one more thing, once all the above is completed, then each batch produced must be tested for identity, purity and potency to make sure everyone receives a quality product. As you can imagine, all that takes weeks per batch.

TA: And how long does it take to make mRNA vaccines?

Pancorbo: I am not sure anyone knows this accurately at this point, since no mRNA vaccine has been manufactured before at any scale close to what will be required for COVID-19. I am going to dare say that it will take at least a couple of weeks per batch.

TA: What about adenovirus vaccines?

Pancorbo: Again, we don't have an adenovirus vaccine in the market, so my response is the same as what I said about mRNA vaccines.

TA: How long will it take manufacturers to scale up production once a vaccine has been approved by the FDA?

Pancorbo: Most of the companies you hear about on TV have already started doing this "at risk," so they can manage demand.

At-risk manufacturing means you don't have approval, or you don't know if the vaccine is going to work, but to reduce or eliminate waiting time to get to the market, you move forward with scale up, construction, manufacturing, etc. The risk is that the investment will not be returned if the vaccine is ineffective or if it is not approved.

It may take several years to scale up a production process like this to the levels required for COVID-19. It involves testing production in a larger vessel. Testing the purification equipment in a larger footprint—and this may get tricky as making soup for four people is not the same as making soup for 100 people. Another bottleneck is equipment and raw material availability. Once you find a device that works you cannot really go to your local grocery store to get one. The same is true for the basic raw materials and supplies—both need time to react to the larger demand.

TA: How much vaccine manufacturing takes place in the U.S.? Do we rely on importing vaccines, or do we have the capacity to make our own?

Pancorbo: Not much vaccine manufacturing takes place in the U.S., really. Traditionally, vaccines were manufactured in other places around the world. After the 2009 flu pandemic our government put a considerable investment into increasing vaccine manufacturing in the U.S., but the larger manufacturers—like Sanofi—are headquartered outside our borders.

TA: How long do you think it will take manufacturers to make enough vaccine to reach everyone who can be vaccinated?

Pancorbo: I would think it will take until late 2021 or mid-2022 to see a significant amount of the population vaccinated.

TA: Will you get the vaccine once it's available?

Pancorbo: Yes. The approval process followed by FDA is very thorough and trustworthy. And, particularly for COVID-19, a lot of information about the vaccine candidates has been made public from early on, which gives me an additional confidence in the process.