COVID19 and its legacy

Andrew J Pollard
Ashall Professor of Infection and Immunity
University of Oxford
 Weymouth
https://wdlh.co.uk/
© Christopher Furlong/Getty
 The Black Death

Plague Pit Science.org

NYT 11/1/20
 Oxford Vaccine
Chimpanzee adenovirus (ChadOx1)
SARS-CoV2 spike protein
Non-replicating
MERS spread
MERS
BBC News
 What it takes to make a
vaccine

Licensure Policy

Clinical Trials 1-2 years

Manufacturing

10-15 years
R&D
Up to decades
 Oxford COVID19 Vaccine Development
Sequence arrives First dose in vial Phase I/II trial
1077 UK Interim results
11/1/20 2/4/2020 23/4/2020
23/11/2020

Pre-GMP 1 or 2 dose schedule Regulatory submission

Brazil

South
UK
Africa
Animal studies

Manufacturing starts Vaccine released to trial Phase II/III trials MHRA EUA
16/3/2020 22/4/2020 Phase II on 28/5/2020 30/12/2020
Phase III on 01/06/2020

Preclinical – 10 years? Pre GMP and Manufacturing - 3 months Clinical trials - 7 months Regulatory – 1 month
 Capability and teams
Air Traffic control
Typhoid Clinical Trials Unit
Phase Ib-III TB
Meningococcus Ebola Influenza Phase I-III
Phase I
Malaria Phase I-II Phase I-IIb MERS
Phase I-III Phase I CCHF
Preclinical
Plague
Phase I

COVID19
 Neutralising antibody and T cell
responses
Antibody T cells

SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2.

Folegatti PM et al. Lancet. 2020;396:467–478. https://dx.doi.org/10.1016/S0140-6736(20)31604-4 Folegatti et al, Lancet
 Oxford COVID19 Vaccine Development
Sequence arrives First dose in vial Phase I/II trial
1077 UK Interim results
11/1/20 2/4/2020 23/4/2020
23/11/2020

Pre-GMP 1 or 2 dose schedule Regulatory submission

Brazil

South
UK
Africa
Animal studies

Manufacturing starts Vaccine released to trial Phase II/III trials MHRA EUA
16/3/2020 22/4/2020 Phase II on 28/5/2020 30/12/2020
Phase III on 01/06/2020

Preclinical – 10 years? Pre GMP and Manufacturing - 3 months Clinical trials - 7 months Regulatory – 1 month
 Similar “live” virus neutralising antibody
across all age groups after boost (>18 years)

Boost

No boost

Prime Boost SD = standard dose of 5x1010 vp

MNA80 = microneutralization assay 80; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2.
Ramasamy MN et al. Online ahead of print. Lancet. 2020. Ramasamy et al, Lancet 2020
 Oxford COVID19 Vaccine Development
Sequence arrives First dose in vial Phase I/II trial
1077 UK Interim results
11/1/20 2/4/2020 23/4/2020
23/11/2020

Pre-GMP 1 or 2 dose schedule Regulatory submission

Brazil

South
UK
Africa
Animal studies

Manufacturing starts Vaccine released to trial Phase II/III trials MHRA EUA
16/3/2020 22/4/2020 Phase II on 28/5/2020 30/12/2020
Phase III on 01/06/2020

Preclinical – 10 years? Pre GMP and Manufacturing - 3 months Clinical trials - 7 months Regulatory – 1 month
 COVID19 partnership
Russia

UK

USA Japan

India

Brazil

This Photo by Unknown Author is licensed under CC BY-SA

South Africa
 Timeline in 2021
MHRA • 30/12/2020

First dose •4/1/2021

given

EMA • 29/1/2021

WHO SAGE • 8/2/2021

WHO PQ •15/2/2021

First COVAX
shipped •24/2/2021
Variants
 Original Alpha
SARSCoV2
COVID19 deaths

1st/2nd dose
Vaccinations

Delta Omicron
Up to 19·8 million deaths averted in 2021

Watson et al, Lancet Infect Dis 2022

 Deaths averted by vaccine

AstraZeneca and Pfizer/BioNTech saved over 12 million lives in

the first year of vaccination | Airfinity Airfinity 2022, The Economist July 13th 2022
 For mild infection there is a clear
correlation of protection with level of
antibody

Nature Medicine 2021

Hamster
Alpha
challenge model
Beta
 Immune responses to prevent severe
COVID19 of the lung are unknown

– but not an issue today?

T cells?
Antibody functions that are non-neutralising
 Real world data
• Limitations in observational studies – bias

• Control group problems – the counterfactual

• Severe disease is not the same

• Useful to monitor effectiveness in the population

Case definitions
Case Definitions matter

Incidental infection

Cofactor in admission
 Original Alpha
SARSCoV2
COVID19 deaths

1st/2nd dose
Vaccinations

Delta Omicron
Viewhub, Johns Hopkins
Omicron - Coronavac
 A changed world

1348 2020

Pandemics
1348-2020

• Plague
• Cholera
• Influenza ++
• Smallpox
50% mortality • HIV <1% mortality
BBC.co.uk
 349 COVID19 vaccines in
development

Scientific challenge

Operational challenges

Funding

Manufacturing
Outbreak news
 Pandemic Threats
1. Disease X 13. Andes Virus Infection (Hantavirus)
2. Pandemic Influenza; 14. Middle East Respiratory Syndrome (MERS) *
3. Novel coronavirus; 15. Monkeypox (MPX);
4. Novel enterovirus 16. Nipah Virus Infection; *
5. Argentine Haemorrhagic Fever (Junin virus); 17. Pneumonic plague (Yersinia pestis);
6. Bolivian Haemorrhagic Fever (Machupo virus); 18. Severe Acute Respiratory Syndrome (SARS); *
7. Crimean Congo Haemorrhagic Fever (CCHF); * 19. Shiga Toxin producing Escherichia coli (STEC).
8. Ebola Virus Disease (EVD); * 20. Rift Valley Fever *
9. Lassa Fever; * 21. Chikungunya *
10. Lujo Virus Disease; 22. Zika *
11. Marburg Virus Disease (MVD); * 23. ………100
12. Severe Fever with Thrombocytopaenia Syndrome
(SFTS); *
UK Vaccine Network
Priority pathogen list: viruses
Priority families : Exemplar pathogens

•Arenaviridae: Lassa fever virus

•Coronaviridae: Middle East respiratory syndrome (MERS)
•Filoviridae: Marburg virus, Sudan ebolavirus
•Flaviridae: Zika virus
•Hantaviridae: Hantaan virus
•Nairoviridae: Crimean Congo Hemorrhagic Fever (CCHF) virus
•Paramyxoviridae: Nipah virus
•Phenuiviridae: Rift Valley Fever (RVF) virus; Dabie bandavirus
(formerly severe fever with thombocytopenia syndrome virus)
•Picornaviridae: Enterovirus 68
•Togaviridae: Chikungunya virus

Priority pathogen list: bacteria

Priority families: Exemplar pathogens

•Coxiellaceae: Q fever (Coxiella burnetii)

•Yersiniaceae: Plague (Yersinia pestis)
 The platform technologies
Moderna,
RNA vaccine Eg COVID19
mRNA
access Protein vaccine
DNA vaccine
Eg Hepatitis B, HPV, Influenza, pertussis,
diphtheria, tetanus

Live virus vaccine

Protein-Polysaccharide Eg MMR, Yellow Fever, varicella
Conjugate vaccine
Eg, Hib, Pneumococcus
ACYW Meningococcus

DNA RNA Protein

ChadOx 1 and Inactivated viral E.g. Polio, COVID19

ChadOx2 vaccine
Viral vector Eg Ebola, COVID19
 Plan trials and funding in
advance
Control Vaccine

Control Vaccine
 Preparedness
• Global surveillance to detect the next pandemic early

• Plan for different types of disease and diseases affecting different populations

• Do our homework on how to make vaccines for different families of bacteria and viruses

• Develop strategies to make and test vaccines faster when a pandemic comes

• Invest in the training of people who will do the stuff that we will need to fight the next pandemic
 Oxford Vaccine Group Investigators

Professor Teresa Lambe OBE Professor Daniela Ferreira Prof Sue Ann Clemens CBE Professor Sir Andrew Pollard
• Respiratory Syncytial • Clostridium difficile
Virus • Congo-Crimean
• Influenza Haemorrhagic Fever
• COVID19 • Marburg
• Pneumococcus • Ebola
• Meningococcus • Lassa Prof. Dr Rinn Song Dr Dominic Kelly Prof. Merryn Voysey
• Pertussis • Nipah Maheshi Ramasamy
• Typhoid Paratyphoid • Malaria
• Non-typhoidal • Middle East Respiratory
salmonella syndrome
• Measles • TB
• Q Fever
• Plague
Prof Daniel O’Connor Prof Samantha Vanderslott
Dr Kat Pollock
 Conclusion

• COVID19 vaccines have had substantial impact

• We know how to prepare for future pandemics

• R&D across families of bacteria and viruses
• Manufacturing capacity
• Planning clinical development
• Regulation
• Continue to improve safety systems for rare events

• Maintain capability through “peacetime” activities across vaccine

development for endemic disease and outbreaks
 Preparedness

Building People Training Programmes