VACCINE IMMUNOLOGY

LECTURE 16, 17/11/2015

• Vaccination – named from the use of vaccinia, or cowpox, to induce immunity to variola (smallpox) in humans.

Vaccination vs. Immunisation

Vaccination is the term used forgiving a vaccine - that is the process of introducing a substance to a host (i.e. Injection or droplets).

Immunisation is the term used for the process of both getting the vaccine and becoming immune to the disease as a result of the vaccine.

Early history of vaccination

• 7th Century - Indian Buddhists drank snake venom (for snakebites).

• 10th/17th Century China – “inoculation or variolation” (for smallpox).

• Variolation (inoculation)- introduced to Europe from Turkey in 1721.

Lady Mary Montague, who witnessed variolation in Istanbul, came back UK and had her daughter inoculated. She then advised the royal family to have their children inoculated .

History of vaccination

As a safeguard, the procedure was first tested on six prisoners (death penalty). All survived and pardoned. Royal children inoculated and survived and variolation became fashionable in Europe.

Edward Jenner

History of vaccination

1 July 1796Jenner used virulent smallpox matter to challenge James Phipps.Experiment successful: Phipps survived many subsequent exposure over 20 yrs

14 May 1796Edward Jenner used material from a cowpox pustule on the hand of Sarah Nelmes to vaccinate James Phipps (8 yr boy).

• 300 million people died of smallpox in the first three-quarter of the 20th Century.

• Smallpox eradicated in 1979 because of mass vaccination programme

Smallpox vaccination

Goals of vaccination

• In individuals - prevention of disease

• In populations - eradication of disease

Immunisation Schedule in Saudi arabia

*BCG (Bacillus Calmette-Guérin) is the current vaccine against TB.

Infant vaccination programmes have saved approx. 3 million deaths worldwide annuallyHepatitis B (900,000),

measles (900,000),

tetanus (400,000),

H. influenzae (400,000),

pertussis (350,000),

yellow fever (30,000),

diphtheria (5,000)

polio (800)

Vaccination saves lives

Major diseases that could be prevented by no effective vaccines

yet

1. ActiveAdministration of antigen (modified infectious agent or toxin) resulting in active production of immunity eg. antibodies

2. PassiveAdministration of antibody-containing serum or sensitised cells

Types of immunisation

Active• natural (unintended)• deliberate - vaccination

Passive

• Placental transfer (IgG)• colostral transfer (IgA)• transfer of human Ig or cells

• Safe - no significant side effects

• Effective, and preferably long-lasting

• Stable in storage

• Cost-effective for the target population

A good vaccine should be:

Types of vaccines

1. Live attenuated vaccines

2. Inactivated vaccines (killed)

3. Subunit vaccines

Types of vaccines

Live attenuated Measles, mumps, rubella, polio, BCG (TB)

Inactivated

Heat killed organisms typhoid, cholera, pertussis

Toxoid (inactive form of toxin, capable of inducing Ab to toxin which causes disease). eg. Diptheria, tetanus

• Polysaccharide (PS), conjugate PS

eg. Pneumococcal PS, meningococcal PS

• Recombinant DNA products / purified proteins

eg. hepatitis B, influenza proteins

Subunit

Types of vaccines

Live vaccines

• single, small dose• given by natural route• local & systemic immunity• resembles natural infection

Advantages

• contaminating virus, • reversion to virulence• inactivation by climatic changes

Disadvantages

Inactivated (killed) vaccines

• safe• stable, so for each batch the safety and efficiency is known

Advantages

• multiple doses and boosters needed• given by injection - unnatural route• high antigen concentration needed• variable efficiency

Disadvantages

Polio Vaccines as a example

• 1958, killed (inactivated) virus ‘Salk’ vaccine introduced, but cannot replicate in cytosol to produce ‘endogenous’ peptides for presentation to CD8+ T cells• 1962, Switched to oral live attenuated virus ‘Sabin’ (OPV) , more potent, but can rarely revert back to a virulent strain causing vaccine associated paralytic polio (VAPP). • 2004, changed to inactivated polio vaccine

Safety

Live vaccines

Killedvaccines

Singleproteins

Immunogenicity

Principles of Vaccination

• To induce a primary response without direct exposure to the infective pathogen

• To induce immune memory so that a more rapid and efficient protective response are induced if the original pathogen is ever encountered again

Vaccination - like a minor infection at an epithelial surface

AntibodyTc-dependent M activationCytotoxic T cells

T cell-mediated immunity

Function of Antibody -1

Opsonisation

IgG1, IgG3, IgG4, IgA

Function of Antibody -2

Function of Antibody -3

Antibody-dependent cellular cytotoxicity(ADCC)

IgG1, IgG3

Function of Antibody -4-Activation of the complement cascade

IgGIgA

IgM

The affinity as well as the amount of antibody increases with repeated immunization

© 2001 by Garland Science

Primary vs Memory response

Adjuvant

immunogen+

adjuvant=

enhancedresponse

• To hold the antigen and release it slowly

• local inflammation, attract immune cells, eg. APC

• enhance Ag uptake, processing and presentation by APC

• promoting local cytokine production

Adjuvants

• Alum. hydroxide suspension• Pertussis toxin - mixed with Diphtheria and Tetanus toxoid DTP triple vaccine

Polysaccharide vaccines

Against Hib, menigococcus, pneumococcus.

Capsular PS, virulence factor

Encapsulated bacteria

Immune response to PS vaccines

1. T cell independent antigen:

• Stimulate B cell for antibody production without T-cell help

2. Poorly immunogenic in infancy

(Not effective in young children)

3. No memory

But Effective in older children and adults

Limitations of polysaccharide vaccines

Making PS Ag T-cell dependent- conjugate vaccines

PS conjugated to a carrier protein to create a “T cell antigen”

polysaccharide

Tetanus toxoid

• T-cells recognise the protein (eg. TT) and activated

• Activated T cells provide signals (eg cytokines) to ‘help’ B-cells to produce antibodies

Conjugate polysaccharide vaccines

Protein Ag attached to PS allow T cells

to help PS-specific B cells.

© 2001 by Garland Science

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Conjugate polysaccharide vaccines

© 2001 by Garland Science

Immune response to Conjugate PS vaccines

Advantages of conjugate vaccines

• More immunogenic than PS vaccines

• Effective in young children as well

• T cell involvement and Immunological memory

• Long-term protection

Limitation of conjugate vaccines

Limited serotype coverage

Increase in non-vaccine serotypes after vaccination

expensive

Herd Immunity

• Unimmunised individuals are also protected against a disease as well as most others immunised in the community.

• Herd immunity needs substantial coverage of population by vaccination.

• If substantial portion of community not immune then introduced virus can circulate and cause disease in nonimmune group.

Passive Immunisation

• Provide antibodies - whole serum orimmunoglobulin (mainly IgG).

• Provide immediate protection, eg rabies, tetanus, diphtheira.

• No long term protection.

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Haemolytic disease in the newborn

RhD- mother with RhD+ fetus can develop anti-Rh antibodies and cause haemolysis to the newborn and subsequent pregnancy.

Antenatal and postnatal administration of anti-RhD

immunoglobuin to RhD- mother can prevent haemolysis in the newborns

SUMMARY

Innate

A r ti f ic ia l N a tu ra l

P ass ive

A r ti f ic ia l N a tu ra l

A ctive

Acuired

Im m unity

The end