nCoV: Rapid Clinical Development of ChAdOx1 nCoV-19

Lead Research Organisation: University of Oxford

Abstract

ChAdOx1 is a safe and effective vaccine vector that can be used to produce vaccines
against many different diseases. Unlike other rapid vaccine technologies, only a single
dose of the vaccine is likely to be needed. DNA, mRNA and recombinant protein vaccines
typically require two or three doses to achieve protective immunity. ChAdOx1 has been
used to make a Middle East Respiratory Syndrome Coronavirus vaccine which is
protective in non-human primates after a single dose, and is safe and highly immunogenic
in humans as demonstrated in a phase I clinical trial. The same vaccine design has been
followed to produce ChAdOx1 nCoV. We now propose to manufacture this vaccine to
cGMP and conduct a clinical trial in healthy volunteers in the UK. We will work closely with
the MHRA to complete all required testing of the vaccine and obtain regulatory approval in
as short a time as possible, with the aim of initiaiting the clinical trial in June.
We will also work with partners to demonstrate protective efficacy of ChAdOx1 nCoV in
two different animal models. This will provide the necessary information to support further
clinical trials of this vaccine to demonstrate efficacy in humans.

Technical Summary

This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project.

ChAdOx1 is a replication-deficient simian adenoviral vector that provides a platform
technology for the production of vaccines against many infectious diseases. For Middle
East Respiratory Syndrome (MERS) coronavirus, a single dose of the ChAdOx1-vectored
MERS vaccine resulted in protection against MERS challenge in non-human primates and
the induction of strong humoral and T cell responses in a Phase I clinical trial. The same
vaccine design has now been followed to produce ChAdOx1 nCoV. Preclinical studies of
the vaccine will be initiated by the end of February. This will include demonstration of
vaccine immunogenicity (antibody and T cell) in mice, followed by vaccine immunogenicity
and efficacy against nCoV-19 challenge in ferrets and non-human primates with
collaborators at PHE Porton Down and NIH. A pre-GMP vaccine seed stock is in
production at Oxford’s GMP manufacturing facility, and will be provided to Advent, Italy,
which will produce the first 1000 doses for clinical studies.
In parallel with preclinical studies and vaccine manufacturing, Oxford will work with the
MHRA on a rapid release testing package. This will employ deep sequencing of the Cell
Harvest and Drug Substance to identify any potential replication competent adenovirus
and adventitious agents rather than following the existing set of in vivo and in vitro assays,
greatly reducing the time to cGMP certification. A phase I/II clinical trial will then be
undertaken to demonstrate vaccine safety and immunogenicity in adults, older adults and
children.

Publications

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publication icon
Van Doremalen N (2020) ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. in bioRxiv : the preprint server for biology