The Backstory: Vaccitech and its role in co-inventing the Oxford COVID-19 vaccine

November 23, 2020

Today (23 November) the University of Oxford, in collaboration with AstraZeneca plc, announced Phase III interim trial data that show its candidate vaccine, ChAdOx1 nCoV-2019, is safe and effective at preventing COVID-19 and offers a high level of protection.  

This vaccine is based on decades of in-depth research, easily distributed and administered it will be transformational over the coming months and years, offering global potential to save lives.

We are immensely proud of our portfolio company, Vaccitech, co-inventors of the Oxford COVID-19 vaccine alongside Oxford University’s Jenner Institute, and the brilliant Oxford academics behind the decades of research that has made this possible.

Vaccitech’s founders, Professors Sarah Gilbert and Adrian Hill, are true pioneers of vaccine technology; responsible for the creation of Vaccitech’s ChAdOx platform and the MERS vaccine that enabled Oxford scientists to respond at speed, creating a safe and effective vaccine for a novel infectious disease – COVID-19 – in months rather than years.

The first human cases of COVID-19 were reported by officials in Wuhan City, China in December 2019. Only one month later on 30 January 2020, the World Health Organisation declared the outbreak a Public Health Emergency of International Concern (PHEIC). In just a few short months, a small cluster of cases quickly evolved into a global pandemic and changed life as we know it.

Yet behind the scenes, Oxford academics had been preparing for just this type of scenario for years.

In 2011 the International Health Regulations Review Committee had declared: “The world is ill-prepared to respond to a severe influenza pandemic or to any similar global, sustained and threatening public-health emergency.”

Three major outbreaks – SARS in 2002, MERS in 2012 and Ebola in 2014 – heightened the threat of a global pandemic and again made it blatantly clear there was a need to invest in vaccine research. Unfortunately, until this current pandemic, vaccine research has been notoriously underfunded. Most research takes place in universities and relies solely on public funding, with private capital reluctant to invest.

But at OSI we are focused on solving the world’s toughest problems and ensuring Oxford’s world-leading science moves out of the laboratory and onto the global stage, where it can make a real-world impact.

This investment enabled the development of vaccines for known pathogens (e.g. MERS) and vaccine platform technologies that would allow us to move at pace when faced with an unexpected or novel infectious disease, for example COVID-19.

As such it is no accident that not one, but two, of the 50 vaccine candidates currently undertaking human trials originated from Oxford research and companies from within our own portfolio.

This is the story of Vaccitech, its founders and their role in co-inventing the Oxford COVID-19 vaccine.  

Vaccitech is a clinical stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases and cancer.

OSI has invested in Vaccitech since its inception, founding and creating the business in 2016 alongside Professors Sarah Gilbert and Adrian Hill – as a spin-out company from the University of Oxford’s Jenner Institute, one of the most prestigious vaccine research centres in the world – and helping to fund the development of the underlying platform technology, subsequent research into novel immunotherapies and vaccines, and build a world-class team.

The team now includes leading authorities across the fields of virology, vaccines and manufacturing with decades of experience developing therapeutic and prophylactic medicines from biotech and pharma.

These focussed efforts and investment have resulted in a pipeline of products that are now in clinical trials against a number of infectious diseases and cancer, including: hepatitis B (HBV), human papillomavirus (HPV), prostate cancer and Middle East Respiratory Syndrome (MERS) – another coronavirus.

The ground-breaking Oxford science behind the company

Our immune system has two arms for fighting off infectious diseases: humoral (utilising antibodies) and cell mediated immunity (utilising T cells).

Traditional vaccine research focusses on teaching the immune system to mount an antibody response to a specific infectious agent. However, once viruses enter cells, they can only be eliminated by destruction of the infected cells in which they replicate. Enter T Cells.

T cells are a diverse and important group of lymphocytes, the most well-known are CD4+ T cells, helper T cells, that lead the fight against infections, and CD8+ T cells, cytotoxic T cells, capable of killing cancer and other invaders.

Diseases associated with persistent or chronic viral infection – for example hepatitis B (HBV), human papillomavirus (HPV) – and mutated proteins, such as cancer, require treatments that create powerful and durable T cell-mediated immune responses, and in particular CD8+ T cell responses.

CD8+ T cell responses have proven notoriously difficult to induce in patients. However, extensive research by Vaccitech founders, Professors Sarah Gilbert and Adrian Hill at the Jenner Institute, led to the design of Vaccitech’s viral vector platform – unique in its ability to induce not only antibodies, but also to induce and maintain superior levels of disease-specific CD8+ T cells in humans.

The Vaccitech platform, licensed from Oxford University, involves delivering either:

One viral vector to vaccinate against an infectious disease (ChAdOx – prime)

Two different viral vectors, encoding the same antigen a few weeks to months apart, to treat infectious diseases and cancer (ChAdOx + MVA – prime + boost)

Viruses are used as vectors to deliver genetic material because they are capable of infecting cells, this is vital if we want to initiate not only an antibody but also a T cell response.

Vaccitech’s ‘prime’ viral vector, Chimpanzee Adenovirus Oxford (ChAdoX), is a non-replicating chimpanzee adenoviral vector, a harmless, modified adenovirus that usually causes the common cold in chimpanzees.

The coronavirus pandemic – designing a vaccine at speed

Oxford academics had already focussed on pandemic preparedness using the ChAdOx technology, for Disease X, when COVID-19 emerged in early 2020.

The world now urgently needed a safe, low-cost, highly effective vaccine for a novel coronavirus which could be rapidly manufactured to produce millions, potentially billions, of doses and easily distributed to bring an end to the pandemic and re-establish a safe, normal society – saving lives and the economy.

As soon as the genetic sequence for coronavirus was released from China in January 2020, technical expertise and clinical data leveraged from development of Vaccitech’s MERS vaccine was instrumental in enabling the Oxford COVID-19 vaccine team, led by Professors Sarah Gilbert and Adrian Hill, to move quickly.

Vaccitech and Oxford researchers had already proven that the ChAdOx platform could generate a strong immune response and had an effective antigen and dose selection strategy for producing a safe, strong immune response against MERS, another coronavirus, based on clinical data from the MERS trials.

ChAdOx was also chosen as the most suitable vaccine technology for COVID-19 because it is unable to replicate, making it safe for children, the elderly and anyone with a pre-existing condition.

Oxford’s vaccine (now known as AZD1222) uses the established ChAdOx technology, specifically ChAdOX1, encoded with the genetic sequence of the spike protein that appears on the surface of coronavirus – responsible for receptor binding and entry into human cells. The same viral vector platform and equivalent spike protein as Vaccitech’s MERS vaccine.

The coronavirus pandemic – developing and manufacturing a vaccine at speed

The focus next was to develop, manufacture at scale and deliver the vaccine to as many people as possible around the world, as quickly as possible on a fair and equal access basis.

It was unanimously agreed that no party should profit from sales of the vaccine during the pandemic and that a large pharma partner provided the best route to ensuring a much-needed vaccine could be delivered to the world.

In the interest of accelerating global vaccine development, Vaccitech assigned its rights to the vaccine candidate to Oxford University Innovation. This enabled Oxford to enter an exclusive global agreement with AstraZeneca; the positive results announced today are a credit to the immense effort and investment that has gone into the clinical trials.

Phase III data is a huge milestone in the fight against COVID-19, the data shows the vaccine candidate is effective at preventing COVID-19 and offers a high level of protection. But crucially the vaccine can be easily administered in existing healthcare systems, stored at ‘fridge temperature’ (2-8°C) and distributed using existing logistics. Large scale manufacturing is ongoing in over 10 countries to support equitable global access.

This is also a monumental moment for Vaccitech’s ChAdOx technology platform. The same platform used for COVID-19 also underpins a broad pipeline of products designed to treat and prevent infectious disease and cancer.

Clinical proof of concept on the world stage, against COVID-19, provides strong scientific validation for Vaccitech’s ChAdOx technology platform and confidence in its broad pipeline of product candidates.

At OSI, we are proud to have played a part in this story and will continue to invest in vaccine technologies and research, ensuring we are ready to act again at speed when the next infectious disease or outbreak emerges.

Vaccitech continues to work in partnership with Oxford University and the Jenner Institute to develop novel products to treat and prevent infectious diseases and cancer. Backed by leading investment institutions, including GV (formerly Google Ventures), Sequoia Capital China, Liontrust (formerly Neptune), Korea Investment Partners and Oxford Sciences Innovation.

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