BIOL2022 Immunology,

Infection and Inflammation

Immunological
Memory and
Vaccination
Lecture 1

Join: vevox.app ID: 162-207-226

Dr Charles Birts
email: c.n.birts@soton.ac.uk
1
 ‘Vaccination prevents an estimated 2.5 million deaths per year. But still an estimated
2.1 million people around the world die every year of diseases preventable by widely
used vaccines.1 With an investment of 3 billion USD a year, every child in the
developing world could receive complete immunization coverage.’ 2

The cause of 1.5 million deaths globally

among children that are preventable by
routine vaccination.3

1
World Health Organization. Immunization Against Diseases of Public Health Importance.
2
UNICEF. Immunize Every Child: GAVI Strategy for Immunization Services. 2
3
Black RE et al. (2010) The Lancet 375:1969-1987
Immunological Memory and Vaccination

Aims of these lectures:

• Background on vaccines
• Vaccine development
• How do vaccines work?
- Developing immunological memory
• Vaccination programs and pandemics
• Types of vaccines
• Uses of vaccines
Learning outcomes: After these lectures you should be able to:
1. Describe the difference between passive and active immunity.
2. Explain how vaccines work and the development of immunological
memory.
3. Discuss the different types of vaccines and their clinical applications.
3
Vaccines – a brief history
What are vaccines?
- Generally contain either parts of microbes or whole microbes that have been killed or
weakened so that they don’t cause disease.
- Take advantage of the body’s ability to learn how to eliminate disease causing
pathogens that attack it and develop a memory for future exposures.

- The concept of vaccinations has been around for a long time.

Thucydides Athens 430 B.C.

• Proposed the notion that an affected individual might pass on a disease to another
individual who is not yet affected.
• Recognized that resistance was specific i.e. survivors of the Plague were resistant to
further attacks of the Plague, but not to other diseases.

Smallpox inoculation in China and India 1500s

• Involved grinding up smallpox scabs and blowing into the
nostril.
• Or scratching matter from a smallpox sore into the skin
(scarification). 4
Vaccines – a brief history
Edward Jenner 1790s
• Observed that milkmaids who had contracted
cowpox were immune to the more severe smallpox.
• Inoculated an 8 year old boy with fluid from a
cowpox pustule.
• Six weeks later he intentionally infected boy with
smallpox. As he predicted the boy was now immune.

Louis Pasteur 1880s

• Developed vaccine for cholera in chickens – first
attenuated vaccine.
• Coined the term vaccine from Latin word vacca meaning
cow.
• 1885 administered first vaccine to a human, a young boy
bitten by a rabid dog.

5
Vaccines – a brief history

6
Vaccines

7
Vaccine development

8
 Vaccine Development

Total time of development up to 15 years

(Total investment US$500M – 1Bn)

( Dodet B (2014) Vaccine 32:1624-1629)

• Increased knowledge of key features for T and B-cell epitope recognition enables better vaccine design.
• Optimise for maximum activation of both humoral and cellular immunity.
• Use of adjuvants to help maximise antigen presentation and most productive immune pathways.
9
The Ideal Vaccine
The ideal vaccine should:

(British Medical Bulletin, Volume 62, Issue 1, 1 July 2002, Pages 15–28, https://doi.org/10.1093/bmb/62.1.15) 10
Acquisition of active and passive
immunity
• Immunisation is the process of eliciting a state of protective immunity against a
disease causing pathogen.
Type Acquired through
Passive Immunity Naturally when maternal IgG crosses the placenta.
Maternally produced IgA in breast milk.
Injection with preformed antibodies – antiserum.
Does not activate the host’s natural immune response.
Active Immunity Natural infection.
Vaccination.
Immune system plays an active role through antigen specific T-and B-cell
activation and formation of protective memory cells.

11
Passive immunity
Passive Immunity may be used when:
• Babies born with congenital immune
deficiencies.
• Unvaccinated individuals exposed to botulism,
tetanus, diphtheria, hepatitis, measles and
rabies.
• Antiserum provides antidote against poisonous
venom.
• Exposure to pathogen that can cause death
faster than an immune response can develop
Passive immunity has no memory response –
it does not activate own immune response.

Possible risks of passive immunity:

• Host immune system can mount an anti-isotype response if antibody from another species
– systemic anaphylaxis.
• Activation of complement immune complexes through IgM or IgG – type III hypersensitivity
reactions. 12
Passive immunity

Zmapp is a drug that is

composed of three
humanised monoclonal
antibodies harvested
from mice exposed to
Ebola virus proteins.

13
Covid-19 antibodies

14
Active immunity
• Active immunity can be triggered by either natural infection or artificial exposure to
some form of pathogen e.g. a vaccine.
• The immune system plays an active role by inducing proliferation of T- and B-cells.
• Primary goal of vaccination is to offer long term protection by inducing a memory
response.

• Successful active
immunisation will elicit a
secondary immune
response that eliminates
the pathogen.

15
How do Vaccines work?
• The principle of vaccination is to mimic an infection in such a way to activate host immune
response and induce a long lasting immunological memory.

Innate – Non-antigen specific.

- General immediate
response.
- No immunological
memory.
- NK cells, mast cells,
eosinophils, basophils and
phagocytic cells
(macrophages, neutrophils, DCs).
Adaptive – Specific to antigen.
- Lag time from exposure to

response.
- Immunological memory
after exposure.
(Figure from Pharmaceutical Biotechnology 4th Ed, Crommelin et al. Chpt 22) - T cells and B cells.
16
How do Vaccines work?
• The principle of vaccination is to mimic an infection in such a way to activate host immune
response and induce a long lasting immunological memory.

• Generation of immune response against a pathogen by vaccination follows several distinct steps:

• Uptake of vaccine (consisting of either

the entire pathogen or antigenic
components) by phagocytes.
• Activation and migration of
professional antigen-presenting cells
from infected tissue to peripheral
lymphoid organs.
• Antigen presentation to T cells and B
cells
• Activation of T and B cells
• Long-lasting protection against
pathogen through development of
memory cells.
(Figure from Pharmaceutical Biotechnology 4th Ed, Crommelin et al. Chpt 22)
17
 How do Vaccines work?

https://www.youtube.com/watch?v=kwVfcc1S7IU
A good podcast:
https://www.thenakedscientists.com/podcasts/naked-scientists-podcast/power-vaccines
18
T-cell activation - recap

TCR MHC

CD28 CD80/86

19
 Memory T-cells
• Memory T-cells are more easily activated than naïve cells and are responsible for secondary responses.

Four types of memory cell, all differ in location,

circulation and function:

1. Stem cell memory T cells - found in secondary

lymphoid organs, give rise to central memory T
cells.
2. Central memory T cells – reside in secondary
lymphoid organs.
3. Effector memory T cells – circulate among
tissues.
4. Resident memory T-cells – settle in peripheral
tissue for long term, first cells to respond to re-
infection.

• Regulation of memory T-cell development and

response remain a very active area of research.
20
B-cell activation - recap
antigen
B-cell

B-cell activation
MHCII CD4

Helper T cell

cytokines
TCR

Clonal expansion

21
Memory B-cells Plasma cells
Memory B-cells
• Memory B-cells have longevity and show a rapid and robust response to antigen re-exposure.
• In primary response, naïve follicular B cells are activated in presence of antigen specific T follicular
helper cells (TFH) with in secondary lymphoid organs.

• B cell clonal expansion and

differentiation produces plasma cells
(produce protective antibodies) and
dormant memory cells.

• Affinity maturation occurs within

germinal centres through somatic
hypermutation and selection by TFH
cells.

• Generation of affinity matured

memory B-cells.

(From Kurosaki T et al. (2015) Nat. Rev. Imm. 15:149)

22
Immunological memory
• Immunological memory is the ability of the immune system to respond with greater
vigour upon re-encounter with the same pathogen.

• Memory cells confer immediate protection and generate secondary responses that
are more rapid and of a higher magnitude than primary response.

(From Sallusto F. et al. (2010) Immunity 33:451)

23
Additional reading
• Kuby ‘Immunology’ 8th Edition Chapter 17
• Janeway’s ‘Immunobiology’ Chapter 16
• Federica Sallusto et al. (2010) From Vaccines to Memory and Back.
Immunity 33:451
• Tomohiro Kurosaki et al. (2015) Memory B cells. Nature Reviews
Immunology 15:149
• Srinivasa Bonam et al. (2017) An Overview of Novel Adjuvants
Designed for Improving Vaccine Efficacy. TIPS 38:771
• Jason Rice et al. (2008) DNA vaccines: precision tools for activating
effective immunity against cancer. Nature Reviews Cancer 8:108
• Dominika Hobernik et al. (2018) DNA Vaccines—How Far From
Clinical Use? International Journal of Molecular Sciences 19:3605
• Jeonghwan Kim et al. (2021) Self-assembled mRNA vaccines.
Advanced Drug Delivery Reviews 170:83-112.
• MacLean Sellars et al. (2022) Cancer vaccines: Building a bridge over
troubled waters. Cell 185:2770-2788