How Vaccines Work

Vaccines are:
A way of priming the immune system to provide
protection from disease caused by a pathogen without
subjecting the person to the disease
Vaccines may be:
Passive: Ready-made immunity provided by giving
pre-formed antibodies

Active: Immunity induced by giving a preparation
of antigens to stimulate a protective
immune response with specificity and
memory to a particular infectious
agent
e.g. a bacteria, virus or toxin

Passive Immunity
Provided by administering Immunoglobulins e.g.
Human Normal Immunoglobulin (HNIG), Hepatitis B
immunoglobulin (HBIG), Varicella Zoster
Immunoglobulin(VZIG), Rabies Immunoglobulin etc.

Pros Give rapid protection within 48 hours

Cons Effect lasts only 3-6 months,
involves using a blood derived product
Antibody Preparations
Human source pooled blood preparations from donors
Human Normal Immunoglobulin (HNIG) (for contacts of Hep A, measles,
polio and rubella)
Varicella Zoster Immunoglobulin (VZIG)
Hepatitis B Immunoglobulin (HBIG)
Human Rabies Immunoglobulin (HRIG)
Tetanus Immunoglobulin (TIG)

Monoclonal
Palivizumab (to prevent respiratory syncytial virus (RSV) in children at high
risk of disease)
Animal source
Diphtheria anti-toxin (used for treatment of diphtheria - not prevention)

Active Immunity
Types of Vaccine
Live Attenuated live organism with low virulence
Inactivated organism has no virulence
Inactivated toxins toxoids
Subcellular fraction( including conjugated vaccines) -no virulence
Genetically engineered contains no original antigen product
Conjugation
Some bacteria (e.g. Haemophilus influenzae type b, Neisseria meningitidis,
Streptococcus pneumoniae) have an outer coating of sugar
molecules (called polysaccharides)
Polysaccharide coatings make it difficult for a baby or
young childs immature immune system to see and respond
to the bacterium inside
Polysaccharide vaccines are poorly immunogenic in
children under 2 years old and do not stimulate long term
immunological memory
Conjugate vaccines have enabled us to effectively protect
children against Hib, Men C and pneumococcal diseases
Carrier
protein
Polysaccharide linked to
carrier protein
Conjugate vaccine
Bacteria
Polysaccharide
(sugar) coating
Conjugation
Conjugation is the process of attaching (linking) the
polysaccharide antigen to a protein carrier (e.g. diphtheria or
tetanus) that the infants immune system already recognises in
order to provoke an immune response

Examples of Vaccines
Live attenuated measles, mumps, rubella, oral
polio, BCG, yellow fever,
varicella
Inactivated influenza, rabies, anthrax, IPV,
pertussis
Inactivated toxins tetanus, diphtheria
Subcellular fraction pneumococcal, Hib, Men C
Genetically engineered Hepatitis B
Vaccines Live
(Attenuated)
Killed
(Inactivated)
Toxoids
Viral MMR
Yellow fever
Polio (OPV)
Varicella
Influenza
Polio (IPV)
Hepatitis B
Hepatitis A
Rabies
Japanese encephalitis
Bacterial BCG
Typhoid oral
Pertussis
Typhoid*
Meningococcal C conjugate
Meningococcal A+C*
Pneumococcal*
Pneumococcal conjugate
H influenzae type b (Hib)
Tetanus
Diphtheria
Classification of vaccines
*polysaccharides
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Combination Vaccines
Many vaccines are combined to make it easier to give
several vaccines at one time
Combination vaccines reduce both number of clinic visits
and number of injections needed
Before combination vaccines are licensed, studies are
carried out to ensure that:
- the immune response to any of the combined antigens is just as good as the
response to the individual vaccines
- the rates of adverse reactions are the same as they would be if the vaccines
were administered separately

Active Vaccines
Vaccines Produce:
Humoral immunity (B cell response) i.e. most bacterial
vaccines
OR
Cell-mediated immunity (T cell response) i.e. live
vaccines such as MMR and BCG
Mode of action of vaccines
Toxoids
Bacterial vaccines (in general)


Viral vaccines (in general)


BCG

Vaccines administered orally or
intra-nasally
Antitoxin neutralising antibodies
Multiple antibodies (neutralisation,opsonisation, complement
activation ...)

Multiple antibodies (neutralisation essentially) which act before the
viruses penetrate the cell + cytotoxic T cells

Cellular mediated immunity

Humoral immunity + mucosal immunity (IgA)
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Vaccines Producing Humoral
Immunity
B cells are a type of lymphocyte (white blood cell)
capable of producing antibodies
B cells with the right receptor shape recognise a
vaccine antigen and bind to it
The B cells are activated to produce a clone of
antibodies with the same specificity
Vaccines Producing
Humoral Immunity
The B cells mature and become plasma cells (capable
of excreting 2000 molecules antibody/second) and
memory cells
If the memory cells encounter the antigen again they
will change into plasma cells and produce large
numbers of specific antibodies
The size, specificity and speed of the response will
increase with repeated exposure
B Cells Differentiate into Plasma
Cells and Memory Cells
Help from T Cells in the Humoral
Response

A certain type of T cell (helper or CD4 cell) can help B
cells differentiate into clones
(Where this is an essential element for a particular
vaccine this is termed a T cell dependent response)
Vaccines Producing
Cell- Mediated Immunity
Viral antigens and BCG stimulate a type of T cell
(termed CD8 or cytotoxic) which kills infected cells.
They can also activate macrophages causing
destruction of intracellular pathogens
Certain pathogen specific cytotoxic T cells persist as
memory cells and are able to respond quickly and
effectively if the individual is exposed to the pathogen
again
Principles of vaccination
A
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Time (days) 5
21
Vaccination
Primary antibody response
Memory cells formed (IgM)
PATHOGEN
Secondary antibody response
Rapid and effective response (IgG)
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Primary Immune Response
Primary immune
response develops in the
weeks following first
exposure to an antigen
Mainly IgM antibody

Secondary immune
response is faster and
more powerful

Predominantly IgG antibody

With kind permission from Nick Holmes


With kind permission from Nick Holmes

Live Attenuated Vaccines
Advantage
Potent, response close to the
optimal naturally acquired
immune response
Disadvantage
May reproduce features of the
disease as sub-clinical or mild
form of the infection
May revert to virulent form (e.g.
OPV)
Cannot be given to
immunosuppressed or pregnant
patients


Inactive Vaccines
Advantages
Cannot cause infection
Can be given to
immunosuppressed and
pregnant individuals
Disadvantages
Less immunogenic and require
addition of adjuvants and
booster doses
What is the role of an adjuvant
To enhance the immune response to the vaccines antigen

How?

Mode of actions are not precisely defined:
To carry the vaccine antigen and to slow its release
To provoke a local inflammatory response
e.g. Aluminium hydroxide adjuvant
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COMMONLY ASKED QUESTIONS
WHY DOES PRIMARY COURSE OF
VACCINE START AT 2 MONTHS OF AGE?

Maternal IgG is transferred across the placenta from 16 weeks
gestation

Passively acquired IgG from mother can suppress response to
DTP, Polio, Men C and Hib vaccine for about 2 months

Maternal antibody to measles may interfere for up to a year

Antibody Development by Age
WHY ARE SOME VACCINES GIVEN IN
CONJUGATED FORM?

Children under 2 are unable to mount a T cell
independent B cell response to organisms with
polysaccharide capsules (e.g. Hib, pneumococcus etc)
Conjugating to a protein e.g. diphtheria or tetanus
toxoid converts it to a T cell dependent response
Examples: Hib, Men C vaccine, Prevenar
(pneumococcal vaccine)
WHY ARE GAPS NEEDED BETWEEN
EACH DOSE OF VACCINE?
To allow each immune response to develop e.g. primary
immunisation (1 month)
This allows the next response to be a true secondary response i.e. faster and
bigger and with higher affinity IgG
To avoid immune interference
If another live vaccine is given while the immune system is making a
primary immune response, the activation of the innate immune system
may neutralise the second live vaccine so that it does not work. Hence
we wait 4 weeks to allow the immune system to recover
Human normal immunoglobulin contains antibodies to many infections
including measles. These antibodies will neutralise any live vaccine.
Hence we wait 3 months for the antibody level to fall
Interval Spacing of vaccines
Doses of the same inactivated vaccine 4 weeks apart
(or 8w for PCV)
Live vaccines (same or different) give at same session or 4
weeks apart
No interval need be observed between:
live and inactivated vaccines
doses of different inactivated vaccines

No evidence exists that inactivated vaccines interfere with the immune
response to other inactivated vaccines or to live vaccines. An inactivated
vaccine can be administered either simultaneously or at any time before or
after a different inactivated vaccine or live vaccine
US General Recommendations on Immunization Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR
Recommendations and Reports December 1, 2006 / Vol. 55 / No. RR-15
CAN YOU GIVE TOO MUCH VACCINE?
If already immune, extra vaccine antigen cannot enter
the body
Capacity of immune system is enormous! could
respond to up to 10,000 vaccines at a time
Useful paper: Do multiple vaccines overwhelm or
weaken infants immune system?
P. Offat et al Paediatrics Vol 109 No 1 January 2002
WHAT CONDITIONS CAN AFFECT
RESPONSE TO VACCINES?
Simultaneous administration of immunoglobulin
Immunosuppression
Sickle cell disease and other causes of hyposplenism
Malnutrition and chronic disease
Nephrotic syndrome
Prematurity (some evidence premature babies may
have sub-optimal response to Hib and Hep B vaccines
but should be scheduled on basis of their actual date of
birth)
WHY IN THE GENERAL POPULATION DO
SOME PEOPLE APPEAR TO RESPOND
BETTER TO VACCINES THAN OTHERS?

Antigens that stimulate T cells may be less effective in some
individuals than others (e.g. Hep B vaccine non-responders)
Our genetic make-up influences the precise binding between
antigens and receptors
There may be survival advantages in ensuring that people do not
respond identically to the same infection

WHY DO WE NEED TO GIVE
BOOSTER DOSES?

To boost individual immunity


To maintain herd immunity

ACKNOWLEDGEMENTS AND
REFERENCES
Sanofi Pasteur MSD
Wood. W. Understanding immunology Prentice Hall
Medical Microbiology Mims, Playfair, Roitt, Wakelin and
Williams