VACCINE IMMUNOLOGY Vaccination vs Immunisation Vaccination is the

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VACCINE IMMUNOLOGY

VACCINE IMMUNOLOGY

Vaccination vs. Immunisation Vaccination is the term used forgiving a vaccine - that is

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

Early history of vaccination • 7 th Century - Indian Buddhists drank snake venom

Early history of vaccination • 7 th Century - Indian Buddhists drank snake venom (for snakebites). • 10 th/17 th Century China – “inoculation or variolation” (for smallpox). • Variolation (inoculation)- introduced to Europe from Turkey in 1721.

History of vaccination Lady Mary Montague, who witnessed variolation in Istanbul, came back UK

History of vaccination 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. 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

Edward Jenner

History of vaccination 14 May 1796 Edward Jenner used material from a cowpox pustule

History of vaccination 14 May 1796 Edward Jenner used material from a cowpox pustule on the hand of Sarah Nelmes to vaccinate James Phipps (8 yr boy). 1 July 1796 Jenner used virulent smallpox matter to challenge James Phipps. Experiment successful: Phipps survived many subsequent exposure over 20 yrs

Smallpox vaccination • 300 million people died of smallpox in the first three-quarter of

Smallpox vaccination • 300 million people died of smallpox in the first three-quarter of the 20 th Century. • Smallpox eradicated in 1979 because of mass vaccination programme

Goals of vaccination • In individuals - prevention of disease • In populations -

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.

Immunisation Schedule in Saudi arabia *BCG (Bacillus Calmette-Guérin) is the current vaccine against TB.

Vaccination saves lives Infant vaccination programmes have saved approx. 3 million deaths worldwide annually

Vaccination saves lives Infant vaccination programmes have saved approx. 3 million deaths worldwide annually Hepatitis 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)

Major diseases that could be prevented by no effective vaccines yet

Major diseases that could be prevented by no effective vaccines yet

Types of immunisation 1. Active Administration of antigen (modified infectious agent or toxin) resulting

Types of immunisation 1. Active Administration of antigen (modified infectious agent or toxin) resulting in active production of immunity eg. antibodies 2. Passive Administration of antibody-containing serum or sensitised cells

Active • natural (unintended) • deliberate - vaccination Passive • Placental transfer (Ig. G)

Active • natural (unintended) • deliberate - vaccination Passive • Placental transfer (Ig. G) • colostral transfer (Ig. A) • transfer of human Ig or cells

A good vaccine should be: • Safe - no significant side effects • Effective,

A good vaccine should be: • Safe - no significant side effects • Effective, and preferably long-lasting • Stable in storage • Cost-effective for the target population

Types of vaccines 1. Live attenuated vaccines 2. Inactivated vaccines (killed) 3. Subunit vaccines

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

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

Types of vaccines Subunit • Polysaccharide (PS), conjugate PS eg. Pneumococcal PS, meningococcal PS

Types of vaccines Subunit • Polysaccharide (PS), conjugate PS eg. Pneumococcal PS, meningococcal PS • Recombinant DNA products / purified proteins eg. hepatitis B, influenza proteins

Live vaccines Advantages • single, small dose • given by natural route • local

Live vaccines Advantages • single, small dose • given by natural route • local & systemic immunity • resembles natural infection Disadvantages • contaminating virus, • reversion to virulence • inactivation by climatic changes

Inactivated (killed) vaccines Advantages • safe • stable, so for each batch the safety

Inactivated (killed) vaccines Advantages • safe • stable, so for each batch the safety and efficiency is known Disadvantages • multiple doses and boosters needed • given by injection - unnatural route • high antigen concentration needed • variable efficiency

Polio Vaccines as a example • 1958, killed (inactivated) virus ‘Salk’ vaccine introduced, but

Polio Vaccines as a example • 1958, killed (inactivated) virus ‘Salk’ vaccine introduced, but cannot replicate in cytosol to produce ‘endogenous’ peptides for presentation to CD 8+ 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 Killed vaccines Immunogenicity Single proteins

Safety Live vaccines Killed vaccines Immunogenicity Single proteins

Principles of Vaccination • To induce a primary response without direct exposure to the

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 Antibody Tc-dependent M activation

Vaccination - like a minor infection at an epithelial surface Antibody Tc-dependent M activation Cytotoxic T cells

T cell-mediated immunity

T cell-mediated immunity

Function of Antibody -1

Function of Antibody -1

Function of Antibody -2 Opsonisation Ig. G 1, Ig. G 3, Ig. G 4,

Function of Antibody -2 Opsonisation Ig. G 1, Ig. G 3, Ig. G 4, Ig. A

Function of Antibody -3 Antibody-dependent cellular cytotoxicity(ADCC) Ig. G 1, Ig. G 3

Function of Antibody -3 Antibody-dependent cellular cytotoxicity(ADCC) Ig. G 1, Ig. G 3

Function of Antibody -4 -Activation of the complement cascade Ig. G Ig. A Ig.

Function of Antibody -4 -Activation of the complement cascade Ig. G Ig. A Ig. M

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

The affinity as well as the amount of antibody increases with repeated immunization © 2001 by Garland Science

Primary vs Memory response

Primary vs Memory response

Adjuvant immunogen + adjuvant = enhanced response • To hold the antigen and release

Adjuvant immunogen + adjuvant = enhanced response • 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

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

Polysaccharide vaccines Encapsulated bacteria Against Hib, menigococcus, pneumococcus. Capsular PS, virulence factor

Polysaccharide vaccines Encapsulated bacteria Against Hib, menigococcus, pneumococcus. Capsular PS, virulence factor

Immune response to PS vaccines

Immune response to PS vaccines

Limitations of polysaccharide vaccines 1. T cell independent antigen: • Stimulate B cell for

Limitations of polysaccharide 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

Making PS Ag T-cell dependent - conjugate vaccines � PS conjugated to a carrier

Making PS Ag T-cell dependent - conjugate vaccines � PS conjugated to a carrier protein to create a “T cell antigen” Tetanus toxoid polysaccharide • 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

Conjugate polysaccharide vaccines Protein Ag attached to PS allow T cells to help PS-specific B cells. © 2001 by Garland Science

Conjugate polysaccharide vaccines 39 © 2001 by Garland Science

Conjugate polysaccharide vaccines 39 © 2001 by Garland Science

Immune response to Conjugate PS vaccines

Immune response to Conjugate PS vaccines

Advantages of conjugate vaccines • More immunogenic than PS vaccines • Effective in young

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

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

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 or immunoglobulin (mainly Ig. G). •

Passive Immunisation • Provide antibodies - whole serum or immunoglobulin (mainly Ig. G). • Provide immediate protection, eg rabies, tetanus, diphtheira. • No long term protection.

Haemolytic disease in the newborn 46 Rh. D- mother with Rh. D+ fetus can

Haemolytic disease in the newborn 46 Rh. D- mother with Rh. D+ fetus can develop anti-Rh antibodies and cause haemolysis to the newborn and subsequent pregnancy.

Antenatal and postnatal administration of anti. Rh. D immunoglobuin to Rh. D- mother can

Antenatal and postnatal administration of anti. Rh. D immunoglobuin to Rh. D- mother can prevent haemolysis in the newborns

SUMMARY

SUMMARY

The end

The end