Vaccines - How They Work

8/12/2019 Vaccines - How They Work

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How Vaccines Work


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Vaccines are:

A way of priming the immune system to provide

protection from disease caused by a pathogen withoutsubjecting the person to the disease


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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

memoryto a particular infectious

agent

e.g. a bacteria, virus or toxin


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Passive Immunity

Provided by administering Immunoglobulins e.g.

Human Normal Immunoglobulin (HNIG), Hepatitis Bimmunoglobulin (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


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Antibody Preparations

Human sourcepooled 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)


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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


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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


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Carrierprotein

Polysaccharide linked to

carrier protein

Conjugate vaccineBacteria

Polysaccharide

(sugar) coating

Conjugation

Conjugation is the process of attaching (linking) thepolysaccharide antigen to a protein carrier (e.g. diphtheria ortetanus) that the infants immune system already recognises inorder to provoke an immune response


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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 fractionpneumococcal, Hib, Men CGenetically engineered Hepatitis B


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Vaccines LiveAttenuated)

KilledInactivated)

Toxoids

Viral MMRYellow feverPolio OPV)

Varicella

InfluenzaPolio IPV)Hepatitis BHepatitis A

RabiesJapanese encephalitis

Bacterial BCGTyphoid oral

PertussisTyphoid*

Meningococcal C conjugateMeningococcal A+C*

Pneumococcal*Pneumococcal conjugate

H influenzae type b Hib)

TetanusDiphtheria

Classification of vaccines

*polysaccharides

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Combination Vaccines

Many vaccines are combined to make it easier to giveseveral vaccines at one time

Combination vaccines reduce both number of clinic visits

and number of injections neededBefore combination vaccines are licensed, studies arecarried out to ensure that:

- the immune response to any of the combined antigens is just as good as theresponse to the individual vaccines

- the rates of adverse reactions are the same as they would be if the vaccineswere administered separately


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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


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Mode of action of vaccines

Toxoids

Bacterial vaccines in general)

Viral vaccines in general)

BCG

Vaccines administered orally orintra-nasally

Antitoxin neutralising antibodies

Multiple antibodies neutralisation,opsonisation, complementactivation ...)

Multiple antibodies neutralisation essentially)which act before theviruses 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


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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 theywill change into plasma cells and produce large

numbers of specific antibodies

The size, specificity and speed of the response will

increase with repeated exposure


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B Cells Differentiate into Plasma

Cells and Memory Cells


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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)


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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 pathogensCertain 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


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Principles of vaccination

Antibodyrespon

se

Time (days)5 21

Vaccination

Primary antibody response

Memory cells formed (IgM)

PATHOGEN

Secondary antibody responseRapid and effective response (IgG)

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Primary Immune Response

Primary immuneresponse develops in theweeks following firstexposure to an antigen

Mainly IgM antibody

Secondary immuneresponse is faster and

more powerful

Predominantly IgG antibody

With kind permission from Nick Holmes

With kind permission from Nick Holmes


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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


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Inactive Vaccines

Advantages

Cannot cause infection

Can be given to

immunosuppressed andpregnant individuals

Disadvantages

Less immunogenic and require

addition of adjuvants and

booster doses


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COMMONLY ASKED QUESTIONS


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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


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Antibody Development by Age


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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)


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WHY ARE GAPS NEEDED BETWEEN

EACH DOSE OF VACCINE?

To allow each immune response to develope.g. primaryimmunisation (1 month)

This allows the next response to be a true secondary responsei.e. faster andbigger and with higher affinity IgG

To avoid immune interference

If another live vaccine is given while the immune system is making aprimary immune response, the activation of the innate immune systemmay neutralise the second live vaccine so that it does not work. Hencewe wait 4 weeks to allow the immune system to recover

Human normal immunoglobulin contains antibodies to many infectionsincluding measles. These antibodies will neutralise any live vaccine.Hence we wait 3 months for the antibody level to fall


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Interval Spacing of vaccines

Doses of the sameinactivated vaccine4 weeks apart(or 8w for PCV)

Live vaccines (same or different) give at same session or 4weeks 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 immuneresponse to other inactivated vaccines or to live vaccines. An inactivatedvaccine can be administered either simultaneously or at any time before orafter a different inactivated vaccine or live vaccine

US General Recommendations on Immunization Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWRRecommendations and Reports December 1, 2006 / Vol. 55 / No. RR-15


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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


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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 vaccinesbut should be scheduled on basis of their actual date ofbirth)


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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 betweenantigens and receptors

There may be survival advantages in ensuring that people do not

respond identically to the same infection


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WHY DO WE NEED TO GIVE

BOOSTER DOSES?

To boost individual immunity

To maintain herd immunity


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Vaccines - How They Work

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