nCoV: Rapid Clinical Development of ChAdOx1 nCoV-19
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
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.
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.
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.
People |
ORCID iD |
Sarah Gilbert (Principal Investigator) |
Publications
Kaplonek P
(2023)
ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.
in Nature immunology
Voysey M
(2023)
Persistence of the immune response after two doses of ChAdOx1 nCov-19 (AZD1222): 1 year of follow-up of two randomized controlled trials
in Clinical and Experimental Immunology
Marchevsky NG
(2022)
An exploratory analysis of the response to ChAdOx1 nCoV-19 (AZD1222) vaccine in males and females.
in EBioMedicine
Hodgson SH
(2022)
Incidental findings in UK healthy volunteers screened for a COVID-19 vaccine trial.
in Clinical and translational science
Sharpe HR
(2022)
CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination.
in JCI insight
Ogbe A
(2022)
Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV.
in JCI insight
Flaxman A
(2021)
Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002).
in Lancet (London, England)
Feng S
(2021)
Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection.
in Nature medicine
Madhi SA
(2021)
Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant.
in The New England journal of medicine
Liu C
(2021)
Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum.
in Cell
Barrett JR
(2021)
Author Correction: Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.
in Nature medicine
Van Doremalen N
(2021)
Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques.
in bioRxiv : the preprint server for biology
Vanderslott S
(2021)
Vaccine nationalism and internationalism: perspectives of COVID-19 vaccine trial participants in the United Kingdom
in BMJ Global Health
Spencer AJ
(2021)
Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice.
in Nature communications
Barrett JR
(2021)
Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.
in Nature medicine
Zhou D
(2021)
Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera.
in Cell
Clemens SAC
(2021)
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil.
in Nature communications
Dejnirattisai W
(2021)
Antibody evasion by the P.1 strain of SARS-CoV-2.
in Cell
Ewer KJ
(2021)
T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial.
in Nature medicine
Bewley KR
(2021)
Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques.
in Science advances
Supasa P
(2021)
Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.
in Cell
Hodgson S
(2021)
What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2
in The Lancet Infectious Diseases
Emary KRW
(2021)
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.
in Lancet (London, England)
Lambe T
(2021)
ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models.
in Communications biology
Wouters OJ
(2021)
Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment.
in Lancet (London, England)
Silva-Cayetano A
(2021)
A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice.
in Med (New York, N.Y.)
Voysey M
(2021)
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
in Lancet (London, England)
Van Doremalen N
(2020)
ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.
in Nature
Folegatti PM
(2020)
Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.
in Lancet (London, England)
Van Doremalen N
(2020)
ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques
Description | COV19 OxfordVacc-01 |
Amount | £31,179,621 (GBP) |
Funding ID | COV19 OxfordVacc-01 |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 04/2020 |
End | 03/2022 |
Description | nCoV: Rapid Clinical Development of ChAdOx1 nCoV-19 |
Amount | £2,174,847 (GBP) |
Funding ID | MC_PC_19055 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2020 |
End | 09/2021 |
Description | PHE |
Organisation | Public Health England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Sharing protocols. |
Collaborator Contribution | Same. |
Impact | Ongoing. |
Start Year | 2019 |
Title | ChAdOx1 nCoV-19/AZD1222 |
Description | ChAdOx1 nCoV-19, initially supported by VaxHUb, has been in clinical trials in UK, SA, Brazil, Kenya, US, licensed in 60 countries for emergency use |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Wide-scale adoption |
Year Development Stage Completed | 2020 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | Demonstrated unprecedented speed of platform response. |
URL | https://www.isrctn.com/ISRCTN15281137?q=ChAdOx1%20nCoV-19&filters=&sort=&offset=5&totalResults=5&pag... |
Description | ATOM Festival Abingdon |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Interactive science festival stand focused on how vaccines are made |
Year(s) Of Engagement Activity | 2022 |
Description | All-Party Parliamentary Group on Medical Research |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Aims of the event a) To bring Parliamentarians together with scientists and other life sciences sector representatives to recognise the exceptional efforts that have been made. b) To inform Parliamentarians of how decades of funding and support enabled the UK's broad and diverse medical research base to quickly pivot to tackle the pandemic. c) To highlight to Parliamentarians the importance of stable and sustainable long-term funding in a diversity of research fields, infrastructures, and research workforces to tackle current and future health challenges across the UK and internationally. |
Year(s) Of Engagement Activity | 2022 |
Description | Andrew Marr via BBC 7Feb2021 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Impact unknown but reached a large audience. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.bbc.co.uk/programmes/p09699wz |
Description | BBC Panorama Oxford COVID vaccine documentary |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | The inside story of the development of the Oxford vaccine against Covid-19. Fergus Walsh scrutinises the data that has come out of the trials, and examines the vaccination's efficacy and safety. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.bbc.co.uk/iplayer/episode/m000qdzd/panorama-the-race-for-a-vaccine |
Description | Cheltenham Science Festival Maker Shack |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | The Maker Shack at Cheltenham Science festival encourages interactive science engagement with a 'making theme'. Our 'Vaccine Maker' activity showcased how different vaccines including the Oxford Covid Vaccine were made. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=GLGDG6tbUR4 |
Description | Cheney School Vaccine Hesitancy Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | A 2 hour interactive workshop testing new strategies for discussing vaccine hesitancy with secondary school pupils at the local Cheney School. |
Year(s) Of Engagement Activity | 2022 |
Description | Franco-British Young Leaders Seminar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | The Oxford Covid Vaccine team hosted the Franco-British Young Leaders for a seminar and tour of the Oxford labs. |
Year(s) Of Engagement Activity | 2022 |
URL | https://francobritish.org/en/young-leaders/ |
Description | History of Science Museum - Vaccines study days |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | A series of now bi-yearly events in collaboration with the History of Science Museum including talks on the the development of the Oxford Covid Vaccine, Vaccine Hesitancy workshops and meet the researcher opportunities for local GCSE and A Level students. |
Year(s) Of Engagement Activity | 2022 |
Description | Wychwood School Medical Chemistry Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Support for the local school conference with recorded Keynote introduction from Prof Sarah Gilbert. Promoting the idea that vaccine development and manufacture is a multidisciplinary subject. |
Year(s) Of Engagement Activity | 2022 |
Description | Wycliffe College: Primary School STEM Day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | STEM focused interactive activity day for primary school aged children. The event was hosted by a high school with students taking the role as science facilitators, supported by scientists. Theme was vaccine research. |
Year(s) Of Engagement Activity | 2022 |