Vaccinology in the genome era

The sheer magnitude of what scientific endeavour has achieved in the last 18 months is extraordinary. Less than a year after the world was brought to a standstill by the introduction of a novel strain of coronavirus, highly effective vaccination programmes had already been rolled out globally, marking the world’s fastest ever vaccine development in history.

In the early days of the pandemic, the New York Times estimated that it would take 11 years to develop, test and manufacture a viable vaccine¹. Pfizer researchers predicted that a vaccine may be ready for first approvals in the latter half of 2021². These estimates may seem foreboding in hindsight, but, considering that the typical timeline for vaccine development is between 10 to 15 years³, both forecasts were actually quite optimistic.

To appreciate how far we’ve come, it’s important to understand where we’ve been.

Vaccine development in the old world

Vaccine development traditionally goes through three phases. In the primary exploratory research phase, scientists develop a rationale for a vaccine based on how the infectious organism causes disease. They identify vaccine candidates that can safely trigger an immune response through the creation of antibodies. Researchers look for candidates that have the highest chance of efficacy and the most easily replicable vaccine design.

While there are many different ways to design a vaccine, the most successful techniques have all involved a form of weakened virus. Whether this be created through applying heat, acid or radiation to weaken the pathogen or by using fragments of viral protein, traditional vaccines must be cultivated in non-human tissue over a long period of time. It has typically been the case that the most effective designs have also been the slowest to produce.

After a vetting process, the top vaccine candidates enter the longest and most unpredictable stage of development: clinical testing. The vaccines are evaluated for safety, efficacy and side effects across a wide variety of populations. This second phase is itself split in to three types of trial: the first focus on the strength of the triggered immune response and establishes that the vaccine is safe and effective.

The next trials determine the right dosage and delivery schedules. The final trials determine safety across the vaccine’s primary use population, identifying rare side effects and negative reactions. Finally, the best performing vaccine is selected to be manufactured and distributed for widespread use.

Using this process, it took 28 years to develop a chicken pox vaccine⁴, six years to just isolate and test the very first polio vaccine⁴ and five years for the Ebola vaccine to be approved⁵. The vaccine for mumps became medical textbook legend in 1967 when it was authorised for use in just four years⁶, however, the significant advances in vaccinology that have been achieved in the last year eclipse this milestone.

Vaccine development in the new world

The last decade has been characterised by a wave of technological disruption that continues to transform our lives. With 2020 being the year of accelerated digital adoption, we are now seeing digital transformation at the confluence of genomics and artificial intelligence (AI) shaping modern vaccinology.

Over the last twenty years, the sequencing cost per genome has fallen at an exponential rate even faster than Moore’s Law - a 1960s prediction that the number of transistors per chip doubles every two years, though between 1961 and 2011 the number has doubled every eighteen months⁷.

Sharp criticism from members of the biomedical community greeted the Human Genome Project when it launched 30 years ago⁸. They believed that the hype surrounding the expensive, research-intensive project was undeserved. It would drain the industry of talent and money, steering attention away from smaller, but worthier, biomedical research efforts.

Nonetheless, the ambitious project to decipher all three billion chemical building blocks of humanity’s genetic make-up went ahead and generated the first human genome sequence at a cost of US$3bn⁸. In just 20 years, the cost of DNA sequencing has decreased by a million fold to less than US$300 today⁹, setting in motion a revolution in genomic technology and applications. This falling cost of genomic sequencing has been critical to the race for a COVID-19 vaccine.

Ten days after the Wuhan Municipal Health Commission, in China, reported a cluster of pneumonia cases of unknown origin the cause had been identified as a novel coronavirus. This later became known as COVID-19 and on 11 January 2020 the genetic sequence was uploaded to a publically available online source.

Using only this sequence, pharmaceuticals, biotech firms, researchers and academics all over the world were able to start designing and manufacturing clinical-grade vaccines at record speed. Thanks to advances in genomic sequencing technology, the digital copy of the virus had arrived in labs all over the world before the physical coronavirus had reached western shores. This is a remarkable development.

AI and machine learning

AI has also been critical to the development of the new vaccines. Analysing the genomic sequencing data using machine learning, researchers can monitor how the virus mutates, identifying regions of the virus that are less prone to variation. On the surface of a virus, there are tens of thousands of subcomponents that the immune system can target.

Machine learning systems analysed the sequence of COVID-19, sorting through thousands of components to predict and identify those most likely to trigger a robust immune response. AI has also been used to predict the shape of the virus, giving valuable insight into how best to fight it. It’s also facilitated simultaneous clinical studies worldwide, significantly speeding up the vaccine development process.

Within hours of the genetic sequence of SARS-Cov-2 becoming public, researchers had pinpointed optimised targets. BioNTech’s Ugur Sahin created ten vaccine candidates on his home computer in Germany – before the illness was even seen in the country – simply by plugging the genetic sequence in to the company’s software¹⁵.

Likewise, Moderna had designed the entire chemical structure of their vaccine candidate in just 48 hours¹⁶. This was then injected in to a patient’s arm as part of clinical testing just two months later, and is the exact same vaccine that was later approved by the US Food and Drug Administration (FDA). The fact that neither BioNTech nor Moderna ever needed to see a physical copy of the virus for this to happen represents the momentous power of mRNA technology.

Looking forward to a healthier future

As we emerge from the pandemic, we’ll look back at the tremendous innovation borne out of the crisis. With mRNA technology by our side, producing vaccines in the future is expected to be far easier, the only difference being in the combination of the four letters of life. In the case of coronavirus variants, the genetic codes of the mutations are expected to make it relatively simple to adjust the vaccine. Preliminary research indicates that future novel virus outbreaks could be tackled by simply swapping out genetic material from different viruses into the same vaccine design²⁰.

In fact, mRNA technology is likely to become a cornerstone in medicine and public health that goes far beyond the current pandemic. The mRNA vaccines that have come to market represent a transformative shift in drug development: moving from a world of pipettes and lab benches growing vaccines to a world of efficient machines printing vaccines.

Contrasting with traditional biotech laboratories, the labs that create mRNA are made up of rows of computers, robots and printers; effectively a digital assembly line for designing and manufacturing mRNA molecules based on AI and machine learning inputs developed from genomic sequencing data.

The plug-and-play ability of the gene-based technology can not only be used to respond to other infectious diseases, but could also provide treatments for conditions such as heart disease and cancer. It can also support treatments for rare medical conditions that were previously too costly to invest in. This breakthrough in scientific research paves the way for many more.

While the pandemic will come to an end, it’s legacy will be long-lasting. If we can consolidate the successes, learn from the failures, strengthen the systems of global scientific collaboration and harness the incredible innovations that have come out of the COVID-19 crisis, it is within our reach to keep the next pandemic so contained that future generations won’t even know its name.

Case studies

As medicine, science and technology have come together to fight COVID-19, the role of investors in allocating capital to companies that can provide innovative solutions has been critical. Across our sustainable portfolio, we’ve invested in a breadth of companies that have been essential to finding the vaccines so desperately needed to emerge from the pandemic. The companies below are illustrative examples of organisations that are fundamental to the fight against COVID-19.

Unless otherwise stated, companies referenced in this report were companies held by our Sustainable Total Return Strategy as of 31 December 2020 and may no longer form part of our portfolios. Reference to specific companies in this report is not an opinion as to their present or future value and should not be considered investment advice or a personal recommendation. They’re included in this report to demonstrate the positive impact companies can have.

Life science companies:

Technology companies:

Medical technology and healthcare companies:

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