In this presentation, we discuss the clinical trial process for the new Covid-19 vaccines. We discuss the different vaccine types. We also discuss the Covid-19 vaccines that the UK is currently using in the NHS, as well as vaccines likely to be used in the next year.

1. COVID-19 Vaccines
Dr Tatiana Christmas & Professor Azeem Majeed
Department of Primary Care and Public Health
NIHR Applied Research Collaboration NW London
Imperial College London
19 JANUARY 2021

2. Contents
 Background on the clinical trial process
 Background on vaccine types
 COVID-19 Vaccines
o Pfizer-BioNTech vaccine
o Oxford-AstraZeneca vaccine
o Moderna vaccine
o Janssen vaccine
o Novovax vaccine
o GSK/Sanofi vaccine
o Valneva vaccine

3. The Clinical Trial Process
All clinical trials of new medicines go through a series of phases to test their safety and efficacy. If a vaccine is shown not
to be safe or effective at any point, it will not progress to the next phases.
Pre-clinical Stage: before testing on humans the vaccine is tested using computer simulations, cell-based tests and
animal tests.
Phase 1: (20-100 people). Assesses the safety of the vaccine, but immune response and various aspects of
pharmacokinetics (e.g. absorption) are also examined.
Phase 2: (100-500 people). Assesses the effectiveness of the vaccine, but information on safety, side effects and risks are
also examined
Phase 3: (1000-5000 people). Phase 3 trials are typically RCT where participants receive the vaccine or a placebo. Phase
3 is used to confirm vaccine safety and effectiveness.
Licensing Approval: If a vaccine passes phase 3 the study team can then ask the Medicines and Healthcare Products
Regulatory Agency (MHRA) to give it approval for use.
Phase 4: After approval and vaccine roll-out, the safety, side effects and effectiveness of the vaccine continue to be
studied while it's being used in practice.

4. mRNA Vaccines
Mechanism:
◦ The mRNA corresponds to the virus’s genetic code.
◦ As a vaccine it exploits the host cells to make the
virus’s antigen.
◦ The antigen then triggers an immune response,
producing antibodies, which prepares the immune
system to respond to any future exposure to COVID-19.
Key advantage:
◦ Easy and quick to design.
Key disadvantage:
◦ Not been used before (but has been extensively
researched)
COVID-19 Vaccines using this approach:
◦ Moderna, Pfizer/BioNTech

5. Viral Vector/Adenoviral Vaccine
Mechanism:
◦ Weakened adenovirus acts as a carrier to deliver the
COVID-19 antigen.
◦ The genes encoding the COVID-19 virus have been
inserted into the adenovirus’s genetic code, the vaccine
uses the host’s cells to manufacture the antigen.
Key advantages:
o Good for large scale manufacturing
Key disadvantages:
◦ Important to pick a vector that’s truly safe. An immune
response to the viral vector could make the vaccine less
effective.
COVID-19 Vaccines using this approach:
o Oxford/AstraZeneca
o Janssen
Existing vaccines:
o Ebola

6. Live attenuated vaccines
Mechanism:
◦ Contains functioning copies of the virus which have
been weakened (attenuated)
◦ As a vaccine it replicates within the body and induces
an immune response, without causing disease
Key advantage:
◦ Stimulates a robust immune response without causing
serious disease
Key disadvantage:
◦ May cause severe infection in those with a weakened
immune system
COVID-19 Vaccines using this approach:
◦ None of the vaccines due for implementation in the UK
Existing examples:
◦ Influenza, MMR, BCG, Chickenpox

7. Inactivated Whole Virus
Mechanism:
◦ Pathogens are inactivated by heat or chemicals
◦ Inactivation destroys infectivity whilst maintaining
immunogenicity
Key advantage:
◦ Suitable for immunocompromised
Key disadvantage:
◦ Booster dose often required as immunity may not be
lifelong
COVID-19 Vaccines using this approach:
◦ Valneva
Existing vaccines:
o Rabies, hepatitis A

8. Sub-unit/protein adjuvant vaccines
Mechanism:
◦ Composed of protein components of the pathogen
capable of inducing a protective immune response
Key advantage:
◦ Considered to be safer than live attenuated or
inactivated whole vaccines as the risks associated with
handling a live vaccine have been eliminated
Key disadvantage:
◦ Typically more expensive
◦ May require an adjuvant to increase the immune
response
COVID-19 Vaccines using this approach:
◦ Novavax
◦ GSK
Existing vaccines:
o Pertussis

9. COVID-19
Vaccines
 There are over 270 different COVID-19 vaccines being
developed world wide
 The government has deals in place for a total of 357 million
vaccine doses across seven different vaccines
 We will cover key aspects of these seven vaccines, which are
expected to be in use in the NHS within next year

10. Pfizer Vaccine
The Pfizer Vaccine
Name of Vaccine COVID-19 Vaccine BNT162b2
Doses ordered by UK 40 million doses
Stage of development Authorised by MHRA on 02.12.2020 and in use.
Anticipated availability N/A
Efficacy 95% efficacy
Good evidence to suggest the vaccine works equally well in people of all ages, races and
ethnicities
Type of vaccine mRNA vaccine
Doses required Two doses, a minimum of 21 days apart
Storage Kept at -75 ⁰C +/- 15 ⁰C, but can be transported to the vaccine sites in the thawed state
(+2⁰C and +8⁰C – shelf life 5 days)
Any other notes Safety concerns and cautions covered on the next slide

11. Pfizer-BioNTech Vaccine
 Side effects – the main side effects:
o Having a painful, heavy feeling in the arm at the site of injection. (Tends to be worst around 1-2 days
after the vaccine)
o Feeling tired, headache, general aches, mild flu like symptoms (typically resolves after 1-2 days)
 Cautions:
o Severe allergies: people with a history of anaphylaxis to a vaccine, medication or food should not have
the Pfizer COVID-19 Vaccine
o Previous anaphylactoid reaction to the Pfizer COVID-19 vaccine: people who have had a previous
anaphylactoid reaction to the Pfizer COVID-19 vaccine should not have the vaccine again
o Pregnancy: women who are pregnant should have the vaccine after the pregnancy has completed
o Breastfeeding: women who are breastfeeding should have the vaccine after they have stopped
breastfeeding

12. The Pfizer Vaccine:
Clinical Trials
o A total of 43,548 participants were
included in phase 2/3 clinical trials:
o 21,720 received BNT162b2
o 21,728 received placebo.
o The trials took place in six
countries: US, Germany, Brazil,
Argentina, South Africa and Turkey
o Efficacy:
o BNT162b2 was 95% effective in
preventing Covid-19 (95% credible
interval, 90.3 to 97.6).
o Similar vaccine efficacy (generally 90
to 100%) was observed across
subgroups defined by age, sex, race,
ethnicity, baseline body-mass index,
and the presence of coexisting
conditions
Figure 1:
Above - Efficacy of BNT162b2 against Covid-19 after the First Dose.
Below - Covid-19 occurrence at least 7 days after the second dose in participants without evidence of infection
(NEJM: Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine)

13. Pfizer-BioNTech Vaccine: Clinical Trials
Safety:
Participants were followed for safety and for the
development of symptomatic Covid-19 for a median
of 2 months.
Limitations and remaining questions:
Further study is required to understand the
following:
• Safety and efficacy beyond 2 months and in
groups not included in this trial (e.g., children,
pregnant women, and immunocompromised
persons).
• Whether the vaccine protects against
asymptomatic infection and transmission to
unvaccinated persons.
• How to deal with those who miss the second
vaccine dose.

14. Oxford-AstraZeneca Vaccine
The Oxford-AstraZeneca Vaccine
Name of Vaccine Covid-19 Vaccine ChAdOx1
Doses ordered by UK 100 million
Stage of development Currently under review by MHRA
Anticipated availability Late 2020/Early 2021
Efficacy Overall efficacy rate of the vaccine is reported as 70%
• 90% effective when given as a half dose before a full-dose booster
• 62% effective when given as two full doses
Type of vaccine Viral vector vaccine
Doses required Two doses given 28 days apart
Storage Can be kept at refrigerated temperatures
Any other notes It is being promoted as a non-profit vaccine aiming for global supply, equity and
commitment to low-income and middle-income countries.

15. The Astrazeneca
Vaccine: Clinical
Trials
o 23 848 participants were enrolled
in the trials
o 11 636 participants (7548 in the
UK, 4088 in Brazil) were included in
the interim primary efficacy analysis.
o Efficacy
o In participants who received two
standard doses, vaccine efficacy
was 62·1% (95% CI 41·0–75·7)
o In participants who received a
low dose followed by a standard
dose, efficacy was 90·0% (95% CI
67·4–97·0)
o Overall vaccine efficacy across
both groups was 70·4% (95·8% CI
54·8–80·6)
Figure 2:
areas show 95% CIs. LD/SD=low-dose prime plus
sCumulative incidence of symptomatic COVID-19 after two doses of vaccine vs
placebo. Blue and red shaded tandard-dose boost. MenACWY=meningococcal group
A, C, W, and Y conjugate vaccine.

16. Moderna Vaccine
The Moderna Vaccine
Name of vaccine mRNA-1273
Doses ordered by UK 11 million
Stage of development Currently under review by MHRA
Anticipated availability Spring 2021
Efficacy 95% efficacy
Type of vaccine mRNA vaccine
Doses required Two doses, 28 days apart
Storage Kept at - 20 ⁰C , but will remain stable for 30 days in refrigerated temperatures
Any other notes Has already been authorised for use in the USA

17. Janssen Vaccine
The Janssen Vaccine (Johnson & Johnson)
Name of vaccine Ad26.COV2.S
Doses ordered by UK 30 million
Stage of development Phase 3 clinical trials
Anticipated availability Mid-2021
Efficacy Exact numbers have not been published
Type of vaccine Adenoviral vector vaccine
Doses required 1 or 2 doses (8 weeks apart), depending on results of trials
Storage Kept at - 20 ⁰C , but will remain stable for at least 3 months in refrigerated
temperatures

18. Novavax Vaccine
Novavax
Name of vaccine NVX-CoV2373
Doses ordered by UK 60 million
Stage of development Phase 3 Clinical Trials
Anticipated availability Mid-2021
Efficacy Exact numbers have not been published
Type of vaccine Protein adjuvant vaccine
Doses required Two doses, 21 days apart
Storage +2⁰C and +8⁰C

19. GSK/Sanofi Vaccine
GSK/Sanofi Vaccine
Doses ordered by UK 60 million
Stage of development Phase 1/Phase 2 clinical trials
Anticipated availability End of 2021
Efficacy Exact numbers have not been published
Type of vaccine Protein adjuvant vaccine
Doses required One or two doses, depending on result of trials
Storage The anticipated roll out of the GSK/Sanofi has been delayed to the end of 2021 after
phase 1/phase 2 demonstrated a lower immune response in older adults. The
company feel they can improve the vaccine.

20. Valneva vaccine
Valneva
Name of Vaccine VLA2001
Doses ordered by UK 60 million
Stage of development Clinical Trials initiated on 16.12.2020
Anticipated availability End of 2021
Efficacy Unknown
Type of vaccine Inactivated whole virus vaccine
Doses required Two doses
Storage Expected to be stored between +2⁰C and +8⁰C

21. Summary
• We have spoken around the clinical trial process
• We have also spoken around different vaccine types
• We have covered key COVID-19 vaccines which the UK is using in the NHS , as well as vaccines likely
to be used in the next year:
o Pfizer vaccine
o Oxford-AstraZeneca vaccine
o Moderna vaccine
o Janssen vaccine
o Novovax vaccine
o GSK/Sanofi vaccine
o Valneva vaccine

22. Any questions?

23. References/Further Reading
1) Public Health England: Covid-19 Vaccination Programme. Information for Healthcare workers.
Access here.
2) GPonline: Which COVID-19 vaccines are lined up for roll-out on the NHS?
3) Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine | NEJM
4) 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 - The Lancet
5) Vaccination : Principle, Types and Mechanism of strengthening Immune system – The Science
Notes