Summary of the book "Vaxxers" - By Professor Sarah Gilbert, Dr Catherine Green

Key concepts in this book:

1. For years, scientists had been studying viral epidemics and creating vaccinations before COVID-19 was discovered.
2. The Ebola vaccine project opened the door for improved vaccine technologies.
3. The MERS vaccine ChAdOx1 served as a model for the SARS-CoV-2 vaccination.
4. Moving from stage to stage "at-risk" cut the time it took to develop the COVID-19 vaccine in half.
5. Working with companies like AstraZeneca and others supplied the financing and equipment needed to produce hundreds of millions of vaccine doses.
6. Prior to its general introduction, the vaccine underwent extensive testing to guarantee its safety and efficacy.
7. The world has to upgrade its research and manufacturing infrastructure, public health response mechanisms, and global cooperation to prepare for Disease Y.

Who can benefit the most from this book:

• Anyone fascinated by vaccine development.
• Public health enthusiasts.
• Futurists looking to prepare for the next big pandemic.

What am I getting out of it? Learn about the development of the Oxford AstraZeneca vaccine.

In late 2019, word got out about a new coronavirus that was rapidly infecting individuals. The SARS-CoV-2 virus was named after it, and the sickness it caused, COVID-19, became one of the worst worldwide health disasters since the 1918 influenza pandemic.

Researchers at the University of Oxford began researching a safe and effective virus vaccine in early 2020, and the Oxford-AstraZeneca COVID-19 vaccine was released at record speed. Dr Catherine Green and Professor Sarah Gilbert, the research team's leaders, were there every step of the way.

You'll learn how they sped up a procedure that normally takes years, as well as what scientists and governments around the world can learn from this experience in order to resist the next deadly epidemic, in this summary.

• You'll learn how outbreaks like SARS, MERS, and Ebola exposed flaws in the global response system.
• What all coronaviruses have in common.
• And how scientists, governments, and public health organizations are already planning for future breakouts in this summary.

1. For years, scientists had been studying viral epidemics and creating vaccinations before COVID-19 was discovered.

Cath Green and a companion were sleeping at a campsite in northwestern Wales when they struck up a discussion with another camper. Cath expressed doubt about the new 5G towers being placed across the UK when she criticized the lack of cell phone signal, despite the fact that no linked health hazards had been discovered.

At the very least, Cath's friend laughed, this individual wasn't claiming that 5G was the source of COVID-19 or that Bill Gates was using vaccines to implant microchips into everyone.

While there may not be a conspiracy, the camper responded that she had no idea what was in the immunizations and didn't trust the folks who made them. These folks were referred to as they by her.

She had no idea that they were referring to Cath. She knew exactly what was in one of the vaccines that were about to be approved. In fact, she was a member of the Oxford University research lab that created it.

The main takeaway is that scientists had been studying viral outbreaks and developing vaccinations for years before COVID-19 was discovered.

To someone like that Welsh camper, the COVID-19 vaccines may appear to have been developed too swiftly and under odd circumstances. However, scientists had been planning for something like COVID for years before the first instance was reported. The virus's official name is SARS-CoV-2, and it isn't the first coronavirus or the first to cause SARS (severe acute respiratory syndrome) in humans.

In November 2002, a previously unknown coronavirus – later dubbed SARS-CoV – was discovered in a Chinese region. It caused pneumonia, and 774 people died as a result of the outbreak, which ended in June 2003. Through the use of traditional procedures like contact tracing and quarantine, public health officials were able to keep the infection from spreading. There was no vaccination, and there was no demand for one at the time. It was unknown whether or not the coronavirus would reappear.

Coronaviruses are frequently detected in bats and, for the most part, remain in bat populations, never reaching humans. Bats are thought to have spread SARS to other species that are more regularly exposed to humans. In 2012, the outbreak of Middle East respiratory disease, often known as MERS-CoV, occurred in the same way. MERS was discovered in camel communities in the Middle East, where it was conveyed to people by vapour droplets released into the air when the camels breathed, sneezed, or coughed.

Scientists and public health organizations learnt more with each epidemic about which responses were most efficient in containing viruses and which needed to be improved.

2. The Ebola vaccine project opened the door for improved vaccine technologies.

The 2014 Ebola outbreak demonstrated that the measures in place to combat fast-spreading diseases were insufficient.

Despite the fact that Ebola outbreaks date back to 1976, there were still no licensed vaccinations or recognized therapies for the disease in 2014, despite the disease's fatality rate of 40 to 50 per cent.

There were numerous Ebola vaccines under development, but only two had been tested on rhesus macaque monkeys, the final step before human trials.

The Ebola virus had already spread across West Africa by April 2015. However, because the number of cases had begun to decline, there were fewer places with high levels of infection suitable for real-world experiments. As a result, scientists were only able to test one vaccination at a time.

This is the most important message: The Ebola vaccine project opened the door for improved vaccine technologies.

Public health groups began testing one Ebola vaccine, known as VSV, in one region in collaboration with labs. Later, the idea was to transition to the second vaccine in development, the ChAd3 EBOZ vaccine. The outbreak was contained by June 2016 thanks to contact tracking, quarantine, and the VSV vaccine. The ChAd3 vaccine was no longer required, and clinical studies were no longer required.

SARS, MERS, and Ebola were among the diseases on the WHO's list of high-priority diseases released in 2016, with the goal of better preparing for the next major outbreak. Sarah, one of the coauthors, and her group at the University of Oxford took advantage of the opportunity to ratchet up work on a comparable vaccine technology called ChAdOx1, which they'd been working on in parallel to the cancelled Ebola research.

ChAdOx1, like the ChAd3 Ebola vaccine, is based on an adenovirus, a virus that produces cold symptoms in people such as runny noses and sore throats. Antibodies against common adenoviruses are already present in the majority of people. That's why chimp adenoviruses, also known as simian adenoviruses, cause humans to have higher immune responses.

The Oxford researchers altered the adenovirus by removing the gene that allows it to replicate and spread throughout a host's body. As a result, it lost its ability to replicate. The gene was then recombined with another gene that instructs infected cells to make the virus's protein. This activates an immune response that produces antibodies to suppress the virus before the receiver is exposed to it; in other words, the body learns to fight the virus without ever being ill. And there it was – the foundation for a replication-deficient recombinant simian adenoviral-vectored vaccine — for Sarah and her team.

They were able to develop a new type of platform technology, which is a predesigned foundation onto which vaccines can be created, by perfecting this process. This would enable them to quickly develop vaccines for additional diseases, including those that do not yet exist.

3. The MERS vaccine ChAdOx1 served as a model for the SARS-CoV-2 vaccination.

Consider the analogy of a baker who delivers birthday cakes with personalized greetings to understand how platform technology works and why it was so valuable in advancing the development of the COVID-19 vaccine.

Let's say you want to order a cake for a birthday party for a friend. You instruct the baker on what to write on the cake and how to adorn it. If the business is slow, the baker now begins the baking and decorating procedure from the beginning. However, if orders begin to pile up, that strategy becomes too time-consuming. Instead, she bakes and ices a large number of cakes every day, then adds personalized messages and finishing touches to each order as they arrive.

The baker may plug in the missing elements and fill orders considerably more quickly by completing the most time-consuming tasks ahead of time.

Professor Gilbert and her team were able to "build the cake" in advance using the ChAdOx1 platform, first creating an influenza vaccine, then a MERS vaccine, and finally moving on to other viruses.

What is the main point here? The MERS vaccine ChAdOx1 served as a model for the SARS-CoV-2 vaccination.

Gilbert and her collaborator, Dr Green of Oxford's Clinical Biomanufacturing Facility, or CBF, were able to improve on their earlier study by employing the same platform for various vaccine development initiatives.

Sarah and Cath were already creating the basis for the vaccination when the WHO added the unknown "Disease X" to their list of priority diseases in 2018. Disease X was the moniker for a possible future virus, the nature of which scientists had no idea. However, SARS-CoV-2 was discovered in humans in late 2019. It became evident as the disease spread that it was Disease X.

They already knew from two successful clinical studies that the MERS vaccine was both safe and effective, even for children, the elderly, and people with preexisting illnesses like diabetes, by the time they developed it. Because MERS is a coronavirus, it also contains a protein known as a spike protein. The genetic sequence of this spike protein was all they needed to begin metaphorically "painting" the new COVID vaccine. On January 10th, 2020, Chinese scientists made this information available online.

Oxford vaccinologists only had to tweak that new genetic coding for the vaccination. The vaccination would then improve the body's response, allowing it to create the identical protein sequence without the virus's harmful effects. They have already designed the exact DNA sequence for the vaccine less than two days after the novel coronavirus's genetic code was made public.

4. Moving from stage to stage "at-risk" cut the time it took to develop the COVID-19 vaccine in half.

Sarah, Cath, and their Oxford teams were already hard at work developing the vaccine – and appealing for funding – by the end of January 2020. Because the labs' capacity was restricted and COVID-19 took precedence, they had to put other vaccine development projects on hold. The process of "decorating the cake" — that is, adding the virus's unique genetic material to the ChAdOx1 platform - consists of multiple steps. Normally, each of these phases would take months or even years to complete, and the financing applications alone would necessitate a significant amount of time in between.

However, with this new quick technique of development, Sarah and Cath's teams at the Clinical Biomanufacturing Facility could move on to the next step before all of the previous step's testing was completed - a method known as progressing at risk.

Here's the main point: Moving from stage to stage "at-risk" cut the time it took to develop the COVID-19 vaccine in half.

When scientists talk about proceeding at risk, they're not referring to the vaccine's safety or efficacy, or the safety of those working on it. Rather, the risk is to the time of the researchers. Time is money for labs that rely on external financing.

Here's the problem with this strategy, and why it's so dangerous: if testing is failed, all of the efforts on the stages that follow will be for nought. Scientists must then go back to the previous stage and correct any errors before continuing on. Nonetheless, in the instance of the rapidly spreading COVID-19 pandemic, the potential reward outweighed the risk; if all tests were successful, millions of more lives may be saved.

They decided to take a chance, and it paid off. The initial stages of development went smoothly, and cells infected with the modified SARS-CoV-2 virus were ready for harvesting and purification. The cells were placed in a centrifuge and spun for two hours at 154,000 Gs to eliminate the sections of the cells that the researchers didn't want. For comparison, the fastest roller coaster produces a G-force of only 6.3.

Finally, on April 2nd, 2020, CBF employees began filling vials with the purified vaccines, labelling them, and testing each vial for sterility. It took only 65 days from the time they devised the vaccine in January to the time they finished labelling and testing the vials. The vaccine manufacturing process has reached a point where it could be scaled up.

5. Working with companies like AstraZeneca and others supplied the financing and equipment needed to produce hundreds of millions of vaccine doses.

The number of lives saved by a vaccine is determined not only by its efficacy in trials, but also by the number of doses available, the number of people who will have access to it, and the number of people who will choose to get vaccinated.

The scientists at the CBF in Oxford needed to create their vaccine on a far greater scale in order for the latter two elements to ever come into play.

They could cultivate ten litres of vaccine culture at a time at the CBF, providing hundreds of doses. The capacity at Advent, their Italian partner facility, was 100 litres of culture, which translates to thousands of doses. This was sufficient for modest trials, but they required the ability to manufacture millions of doses at once.

What is the most important message? Working with companies like AstraZeneca and others supplied the financing and equipment needed to produce hundreds of millions of vaccine doses.

Dr Sandy Douglas, a member of the Oxford team, had thought about the difficulty of scaling up production from the start. He'd devised a method for growing and purifying millions of dosages at once in 1,000-liter bioreactors — basically, huge tanks. Dr Douglas requested financial funding to prove the technique's actual potential after they'd already tested it on a lesser scale.

He successfully tested his large-scale manufacturing approach with 50- and 200-litre tanks at the Pall facility in Portsmouth, UK, with £400,000 in funding. He then received further money from the Vaccine Taskforce of the United Kingdom government. His associates were able to optimize the production procedure as well as test, store, and transport the doses created as a result of this.

Everything was in place by the end of April 2020. The CBF had enough doses for the three phases of human trials, and the systems were in place to create millions more once the vaccine was approved for general use. On April 30th, it was revealed that the institute would form a global production and distribution partnership with AstraZeneca, a significant pharmaceutical company. Orders for billions of doses of the renamed AZD1222 vaccine began coming in from all around the world.

The Oxford-AstraZeneca collaboration resulted in another significant trait that marked their vaccine distinct from the rest of the COVID-19 vaccines: it didn't require ultra-cold storage or transportation. It would be considerably more accessible to sections of the world that didn't have or couldn't afford such facilities since it could be refrigerated routinely - between two and eight degrees Celsius, as the vaccines for polio and measles.

6. Prior to its general introduction, the vaccine underwent extensive testing to guarantee its safety and efficacy.

While it took just over two months to design and manufacture the first COVID-19 vaccinations, it was all in preparation for the penultimate stage before licensing: effectiveness trials. It would take another seven months to complete this step. Fortunately, because the same ChAdOx1 platform had already been used in influenza and MERS vaccines, much of the early dosage testing had already been performed.

However, because this was a brand-new virus with limited information about its behaviour, scientists from the CBF and the University of Oxford's Centre for Clinical Vaccinology and Tropical Medicine, or CCVTM, decided to take extra precautions. If recipients later come into contact with the real virus, certain vaccines have the potential to produce a severe infection.

Here's the main point: Prior to its general introduction, the vaccine underwent extensive testing to guarantee its safety and efficacy.

To be cautious, researchers completed animal experiments before administering a single dosage of the vaccine to humans. Scientists achieved this by vaccinating animals and then exposing them to high levels of the coronavirus. It worked: the vaccine-elicited the desired immunological response. The vaccinated animals also fared substantially better than the unvaccinated animals in the control group. With this news, the Oxford group were given permission to begin planning human trials.

The Phase I trials, which began with only 1000 volunteers, were the first wave of testing. The only purpose was to evaluate if the vaccine elicited a safe immunological response in healthy persons under 55. The vaccination was given to half of the volunteers, while the other half received a placebo. In this double-blind trial, neither the participants nor the nurses who administered the immunizations knew whether they were getting the real thing or a placebo. Every participant kept an online health diary, detailing any health difficulties that emerged. A set of ten volunteers was given a second booster shot four weeks later to evaluate if it boosted their immune response.

The age range of volunteers for the Phase II studies was broadened to include persons aged 56 and up who did not have any preexisting conditions. Finally, persons of any age or health condition were eligible to participate in Phase III.

In the trials, receiving two doses twelve weeks apart resulted in the highest levels of efficacy, reducing infection, transmission, and symptoms in situations of exposure. After thereafter, the trials were expanded to include Brazil and South Africa. The UK's Medicines and Healthcare Products Regulatory Agency, or MHRA, approved the AZD1222 vaccine on December 30th, 2020. On January 4th, 2021, the first dose was given, with hundreds of millions more to follow.

7. The world has to upgrade its research and manufacturing infrastructure, public health response mechanisms, and global cooperation to prepare for Disease Y.

The task of containing the virus — and preparing for the next one – had only just begun with the first immunizations being injected into arms around the world.

Along with the logistical challenges of production and distribution, there was also a more human barrier: global vaccination programs have been received with mistrust in some areas, jeopardizing the vaccine's overall effectiveness.

There's also the matter of variants to consider. A virus's mutation rate increases as it spreads. Some varieties have been proved to be resistant to the vaccine, but others will require updated vaccines.

While certain preparations hastened vaccine development and the global effort to save lives, there is still a long way to go in terms of optimizing processes in the event of the next viral outbreak.

The essential lesson here is that the world needs to upgrade its research and industrial infrastructure, public health response systems, and global cooperation in order to prepare for Disease Y.

Epidemiologists have already gotten a glimpse of what this future hypothetical virus, dubbed Disease Y for the time being, would look like. Industrial farming practices, which frequently keep animals in unclean environments, provide one clue. Viruses spread from one species to another in such circumstances, mutating and eventually reaching humans.

Another coronavirus, such as SARS or MERS, or a new, highly contagious type of influenza virus might be Disease Y. It could also be a virus that no one has ever heard of. Only 267 of the estimated 1.67 million viruses have been investigated by scientists.

Whatever Disease Y turns out to be, it will put the world's response systems to the test once more. During the COVID-19 pandemic, funding and manufacturing infrastructure were major roadblocks. The CBF requested funding for a few million pounds early on. It was regarded as completely unreasonable at the time. But, in retrospect, it's nothing compared to the sums of money spent by governments and corporations to combat the virus. Organizations must also increase the number of programs that stockpile critical equipment, such as personal protective equipment (PPE) for labs and healthcare professionals.

Finally, investing in pandemic preparedness entails improving on the CBF's and others' vaccine development methods. The total pandemic reaction will be that much more effective the next time around if they can speed up the development process even more, and if other vaccines like Pfizer-BioNTech and Moderna can be adjusted to be stored at normal temperatures.

1. The essential takeaway from this summary is that much of the world was caught off guard by the COVID-19 pandemic's issues. Scientists at the University of Oxford, on the other hand, were among those who were planning for an outbreak long before it happened. They created the research foundation essential to generate the ChAdOx1 framework, which manufactures vaccines much more quickly than typical, by producing vaccines against other coronaviruses such as SARS and MERS, as well as Ebola. It's critical to consider the next pandemic after designing, producing, testing and distributing the COVID-19 vaccine. The world will be better prepared to deal with future outbreaks if the infrastructure for vaccine development and worldwide cooperation is improved.