Vaccination

Question 1

Definitions.

Vaccination
Originated from the first attempts to protect people with the first smallpox vaccine – v………….
Also called immunisation
Refers to all procedures to protect people from infection through pa………… or a……….. immunity.
Passive immunity:
Administration of antibodies, eg. Vari……… zo…….. imm……….. (VZIG) given to preg…….. women.
Also by pa……….. of antibodies across the pl…………..

Answer 1

Definitions.

Vaccination
Originated from the first attempts to protect people with the first smallpox vaccine – vaccinia.
Also called immunisation
Refers to all procedures to protect people from infection through passive or active immunity.
Passive immunity:
Administration of antibodies, eg. Varicella zoster immunoglobulin (VZIG) given to pregnant women.
Also by passage of antibodies across the placenta

Question 2

Definitions.

Active immunity is achieved through stimulating the bodies immune system, by:
- Previous I…………………..
- Inactive va………………..
To…………, such as tetanus.
Ina………… organism such as He…………….. A vaccine.
Subunit vaccines such as the ac…….. pert……….. va………..
Recom…………… antigen vaccines.

Modified, attenuated live organism
such as oral polio vaccine or MMR.

Answer 2

Active immunity is achieved through stimulating the bodies immune system, by:
- Previous infection
- Inactive vaccine
Toxoid, such as tetanus.
Inactivated organism such as Hepatitis A vaccine.
Subunit vaccines such as the acellular pertussis vaccine.
Recombinant antigen vaccines.

Modified, attenuated live organism
such as oral polio vaccine or MMR.

Question 3

History of Vaccination.

10th century China
- Variolation.

Inoculation of children with dried material from healed sc………. of mild smallpox cases.

Practice arrived in Eu……… via Tu……… in the early eighteenth century.

Edward Jenner considered to be the father of vaccination.
- He noticed that milkmaids had much better complexions because did not tend to contract sma………

Answer 3

History of Vaccination.

10th century China
Variolation.
Inoculation of children with dried material from healed scabs of mild smallpox cases.
Practice arrived in Europe via Turkey in the early eighteenth century.
Edward Jenner considered to be the father of vaccination.
He noticed that milkmaids had much better complexions because did not tend to contract smallpox.

Question 4

Jenners experiment

1796 inoculated James Phipps (8 years old) with liquid taken from co………. pus…….on the hand of Sarah Nelmes.

The boy was subsequently inoculated with smallpox and did not succ……… to the disease.

Published in book in 1798
- Inoculated thousands of patients in his garden shed in Gloucestershire!

Answer 4

Jenners experiment

1796 inoculated James Phipps (8 years old) with liquid taken from cowpox pustule on the hand of Sarah Nelmes.
The boy was subsequently inoculated with smallpox and did not succumb to the disease.
Published in book in 1798
Inoculated thousands of patients in his garden shed in Gloucestershire!

Question 5

Louis Pasteur and vaccination- 19th century.

Accidental discovery after chic…… experiments into the disease transmission of fo…….. cholera.

• In………… the disease into chickens and they all died.
• Repeated the experiment
• All lived probably because nu……… of ba………… injected was too lo…..
• Vacation and then repeated experiment on same chicken plus two new ones because not enough new ones had been ordered.

Answer 5

Louis Pasteur and vaccination- 19th century.

Accidental discovery after chicken experiments into the disease transmission of fowl cholera.

• Injected the disease into chickens and they all died.
• Repeated the experiment
• All lived probably because number of bacteria injected was too low.
• Vacation and then repeated experiment on same chicken plus two new ones because not enough new ones had been ordered.

Question 6

Development of vaccination

Created vaccines for anthrax and rabies.
1798 sm..............
1885 ra.............
1897 Pl.............
1923 D.................
1926 p................
1927 BC........., tub.............
1927 tet.........,

Answer 6

Development of vaccination

Created vaccines for anthrax and rabies.
1798 smallpox
1885 rabies
1897 Plague
1923 Diphtheria
1926 pertussis
1927 BCG, tuberculosis
1927 tetanus,

Question 7

Development of Vaccination

The early vaccines proved to be reliable
- Considerably reduced the burden of death and disease.

1935 yellow fever vaccine after development of the chori…………….. membrane for culturing viruses.

After the second world war with advances in technology, other vaccines still used today were developed:

• Killed and oral po……… va……………
• Me…….., mu……… and rub………

Answer 7

Development of Vaccination

The early vaccines proved to be reliable
- Considerably reduced the burden of death and disease.

1935 yellow fever vaccine after development of the chorioallantoic membrane for culturing viruses.

After the second world war with advances in technology, other vaccines still used today were developed:

• Killed and oral polio vaccines
• Measles, mumps and rubella.

Question 8

Development of Vaccination

Confined to industrialised countries
- Coverage of Smallpox was pat……… and outbreaks occurred worldwide.

Oral polio va…….. (OPV) became available in 1962
- Previously injectable 1955 vaccine IPV and used widely in schools and clinics.

Hepatitis .. became available in 1981.

Answer 8

Development of Vaccination

Confined to industrialised countries
- Coverage of Smallpox was patchy and outbreaks occurred worldwide.

Oral polio vaccine (OPV) became available in 1962
= Previously injectable 1955 vaccine IPV and used widely in schools and clinics.

Hepatitis B became available in 1981.

Question 9

Purpose of Vaccination

Protecting the individual
- Against non-infe………… diseases such as tetanus

Protecting the population by creating he….. immunity.
- Eg. Mea……….., p……, sma………., mu…….. if >90% of the population are immunised.

Protecting the foetus
- Eg. Rub…….., avoiding congenital abnormalities.

Answer 9

Purpose of Vaccination

Protecting the individual
- Against non-infectious diseases such as tetanus

Protecting the population by creating herd immunity.
- Eg. Measles, polio, smallpox, mumps if >90% of the population are immunised.

Protecting the foetus
- Eg. Rubella, avoiding congenital abnormalities.

Question 10

Purpose of Vaccination

Preventing a serious disease such as:

• Dip………………
• Haem…………. inf……………
• Type ….. meni………..
• Nei……….. meni……… type …

Preventing complications in a less serious disease
- Mea……….

Protecting those at risk due to:

• Age (Strep. Pne………..)
• Occupation (hepatitis …..)
• Travel (hepatitis …, yellow f…..r, typ………).

Answer 10

Purpose of Vaccination

Preventing a serious disease such as:

• Diphtheria
• Haemophilus influenza
• Type B meningitis
• Neisseria meningitidis type C

Preventing complications in a less serious disease
Measles.

Protecting those at risk due to:

• Age (Strep. Pneumoniae)
• Occupation (hepatitis B)
• Travel (hepatitis A, yellow fever, typhoid).

Question 11

Herd immunity.

The level of protection is sufficiently high in the population so that the virus can no longer find and infect those individuals who remain susceptible.
- The susceptible people are indirectly protected from exposure because of the h……… level of I’m………….. in the rest of the community.

If sufficiently high…… the circu………. of the virus is co…………. interrupted.

Low levels of herd immunity will allow the virus to be t………….. at a lower r……….

Answer 11

Herd immunity.

The level of protection is sufficiently high in the population so that the virus can no longer find and infect those individuals who remain susceptible.
- The susceptible people are indirectly protected from exposure because of the high level of immunisation in the rest of the community.

If sufficiently high the circulation of the virus is completely interrupted.

Low levels of herd immunity will allow the virus to be transmitted at a lower rate.

Question 12

Types of vaccine – immune response considerations

All vaccines need to contain appropriate ant……….. to stimulate a protective immune response
- Either ce….. me……….. or an………mediated (Th… or Th….).

T….. stimulates IFN .., IL2 and TNf-B (cell mediated) mac………., den…….. ce……….

Th2 stimulates IL…, IL…, IL…, IL…. and IL…..(………… mediated). …. cells.

Different infections require different immune responses.

Answer 12

Types of vaccine – immune response considerations

All vaccines need to contain appropriate antigens to stimulate a protective immune response
- Either cell mediated or antibody mediated (Th1 or Th2).

Th1 stimulates IFN y, IL2 and TNF-B (cell mediated) macrophages, dendritic cells

Th2 stimulates IL4, IL5, IL9, IL10 and IL13 (antibody mediated). B cells.

Different infections require different immune responses.

Question 13

Types of vaccine – immune response considerations

In practice during an infection many …. cells are stimulated by different anti……..
- The phenotype of the overall Th cell population is determined by the greatest number of ……… of any particular p…………..

Type of response required influ……….. design of new designer vaccines.

Answer 13

Types of vaccine – immune response considerations

In practice during an infection many Th cells are stimulated by different antigens
- The phenotype of the overall Th cell population is determined by the greatest number of cells of any particular phenotype.

Type of response required influences design of new designer vaccines.

Question 14

Traditional vaccines

Live, attenuated.

• Serial passage of a pathogen until pathogen does not kill h…… but can induce ………………..
• Po…………
• Yellow fe………….
• Sm…………. (cowpox/vaccinia)
• My…………………… (BCG)
• C…………… (without cap….).

Answer 14

Traditional vaccines

Live, attenuated.

• Serial passage of a pathogen until pathogen does not kill host but can induce protection.
• Polio
• Yellow fever
• Smallpox (cowpox/vaccinia)
• Mycobacteria (BCG)
• Cholera (without capsule).

Question 15

Live attentuated - polio

Sabin polio
- OP…., grown in monkey epi………. cells.

Provides good production of memory cells.

Given on a sugar cube

• Vi……… colonises int……………..
• Ind……….. protective immunity to all three vir………… strains.
• Secretory Ig…, Ig…. and Ig…. induced.

Answer 15

Live attentuated - polio

Sabin polio
- OPV, grown in monkey epithelial cells.

Provides good production of memory cells.

Given on a sugar cube

• Virus colonises intestine
• Induces protective immunity to all three virulent strains.
• Secretory IgA, IgM and IgG induced.

Question 16

Live Attenuated - Problems

Live vaccines can produce disease:

Po……
- 1 in 2.4 million injections caused disease, especially in areas where clean water is a problem.
- S….. now used, but can be problematic to use worldwide.
Yellow fever vaccine induces disease in HI….. patients.

BC…. can also be problematic for HIV patients

Vaccinia induces disease in immuno-compr……….. patients.

Answer 16

Live Attenuated - Problems

Live vaccines can produce disease:

Polio
- 1 in 2.4 million injections caused disease, especially in areas where clean water is a problem.
- Salk now used, but can be problematic to use worldwide.
Yellow fever vaccine induces disease in HIV+ patients.

BCG can also be problematic for HIV patients

Vaccinia induces disease in immuno-compromised patients.

Question 17

Traditional vaccines

Whole cell killed.

• Pathogen that has been treated with he……. or form……………. and therefore un. to …… cause infection.
• Need to maintain str……… of epi……… on the sure……… antigen du……….. inactivation, without de………. the proteins.
• Form……….. better, used in Sa… polio vaccine.

Influe…, Hep …., pert….. – good

Chole…., plag…., some meaning………… – poor.

Answer 17

Traditional vaccines

Whole cell killed.

• Pathogen that has been treated with heat or formaldehyde and therefore unable to cause infection.
• Need to maintain structure of epitopes on the surface antigen during inactivation, without denaturing the proteins.
• Formaldehyde better, used in Salk polio vaccine.

Influenza, Hep A, pertussis – good

Cholera, plague, some meningococcal – poor.

Question 18

KIlled vaccine - problems

Killed vaccines:

• Do not always work well even when used with adju………. and conj…………
• Can induce a la………. non-specific response.
• Viral vaccines sometimes have a short duration of protection, boo………… required.
• Oral administration only weakly stimulates Ig…. production
• ——–IV no Ig…. at all – necessary for intestinal disease and respiratory disease.

Answer 18

Killed Vaccine - Problems

Killed vaccines:

• Do not always work well even when used with adjuvants and conjugated.
• Can induce a large non-specific response.
• Viral vaccines sometimes have a short duration of protection, boosters required.
• Oral administration only weakly stimulates IgA production
• ———–IV no IgA at all – necessary for intestinal disease and respiratory disease.

Question 19

Traditional vaccines

Toxoid
- Ina…………… form of a t…….. produced by pa…………… ………………:

Dip……….. and Te………… – very good.

Answer 19

Traditional vaccines

Toxoid
- Inactivated form of a toxin produced by pathogenic bacteria:

Diphtheria and Tetanus – very good.

Question 20

Designer Vaccines

The ideal would be a live atte……………. mutant by rational design
-But not available.

Can however purify and de……. vaccines knowing the an………. or ep……….. that will produce the desired resp…….
- S… u….. vac……… (partially puri……. vaccines)

Surface antigens:

Viruses

• Neura……….. and haem…………. from infl………. virus.
• Needs freq……. updating to reflect ant…… sh…. and dri..

Answer 20

Designer Vaccines

The ideal would be a live attenuated mutant by rational design
- But not available.

Can however purify and design vaccines knowing the antigens or epitopes that will produce the desired response
- Sub unit vaccine (partially purifed vaccines)

Surface antigens:

Viruses

• Neuraminidase and haemagglutinin from influenza virus.
• Needs frequent updating to reflect antigen shift and drift.

Question 21

Partially Purified vaccines contd

Bacterial capsules.

• Purified po……….. ph………….. from Haemophilus influ………..
• Nei………… menin………. type …
• Sa…………… typhi – v.. antigen
• Strep………… pneu………. – 23 strains involved, vaccine is a m…… of these …… ant….. (PPV). Also conj…….. vaccine (PCV) contains polysa…………. of 7 common caps…….. types.

Bacterial attachment structures
- per……… of Bo……….. pe……….

Viral glycoproteins also being explored

• H… envelope glycop……..
• HS…….

Answer 21

Partially Purified vaccines contd

Bacterial capsules.

• Purified polyribitol phosphate from Haemophilus influenzae.
• Neisseria meningitidis type C
• Salmonella typhi – vi antigen
• Streptococcus pneumoniae – 23 strains involved, vaccine is a mix of these 23 antigens (PPV). Also conjugate vaccine (PCV) contains polysaccharide of 7 common capsular types.

Bacterial attachment structures
- pertactin of Bordetella pertussis.

Viral glycoproteins also being explored

• HIV envelope glycoprotein
• HSV2.

Question 22

Recombinant Antigen vaccines.

Cl……. genes and express in bacterial y…….. or mam……….. cells.

First one was Hepatitis ….. sur……….. an..
- Cloned in y…….t cells.

Grown in large fermenters

• Ye………. harv……….. and disr………… by high pres……….
• Released reco………. H…….. then purified for use.

Answer 22

Recombinant Antigen vaccines.

Clone genes and express in bacterial yeast or mammalian cells.

First one was Hepatitis B surface antigen
- Cloned in yeast cells.

Grown in large fermenters

• Yeasts harvested and disrupted by high pressure
• Released recombinant Hbsag then purified for use.

Question 23

Recombinant-vector vaccines.

Genes encoding major antigens introduced into attenuated viruses or bacteria.
Vaccinia virus often used
- Ca……….. vi………..
- S.typh……………. engineered with genes of chol………..

Can carry several dozen foreign get…….. with………out losing inf……….. and ability to repl..

Recent example in USA

Yellow fever vaccine engineered to express anti…….. of West Nile virus.

Answer 23

Recombinant-vector vaccines.

Genes encoding major antigens introduced into attenuated viruses or bacteria.
Vaccinia virus often used
- Canarypox virus
- S.typhimurium engineered with genes of cholera.

Can carry several dozen foreign genes without losing infectivity and ability to replicate.

Recent example in USA

Yellow fever vaccine engineered to express antigens of West Nile virus.

Question 24

Designer vaccines -DNA vaccines

DNA vaccines
-Key antigens given as equivalent coding copy of plasmid ………. + pr………………

Injected into muscle.

• DNA taken up by host cells, re…………. and is exp………. on the su…….. over long period.
• Immune cells see antigens in a more rea……… manner and produce appropriate response. Expressed on d………. cells, enh……….. response.
• Antibody and cell-mediated responses.

Answer 24

Designer vaccines -DNA vaccines

DNA vaccines
-Key antigens given as equivalent coding copy of plasmid DNA + promoter.

Injected into muscle.

• DNA taken up by host cells, replicates and is expressed on the surface over long period.
• Immune cells see antigens in a more realistic manner and produce appropriate response. Expressed on dendritic cells, enhances response.
• Antibody and cell-mediated responses.

Question 25

Problems with designer, sub unit vaccinations

Sub-unit vaccines are very time-consuming to make.

Single pro………… may not be as port………….

Mu………. of an……. by pathogen makes vac………. use……….

• Problem with developing a v………. for HIV.
• Also different antigenic expre…….. at diff……….. stages, mala……..

Problems with efficacy in infants because they have under……….. immune response and do not gen…….. good … cell responses to the subunits.

Answer 25

Problems with designer, sub unit vaccinations

Sub-unit vaccines are very time-consuming to make.

Single proteins may not be as protective.

Mutation of antigen by pathogen makes vaccine useless

• Problem with developing a vaccine for HIV.
• Also different antigenic expression at different stages, malaria.

Problems with efficacy in infants because they have underdeveloped immune response and do not generate good T cell responses to the subunits.

Question 26

Methods to improve immunogenicity

Adjuvants.
- Any substance that en……….. the immune response to an ant…….. with which it is mixed.
- Alhy……… – Al (OH)₃ used in human vaccines.
Induces Th…. response.
Anti……. is adsorbed.
Red………. am…….. of ant…. needed,
pro…….. antigen from deg………,
creates an intr…………. antigen
reservoir and en………… ly………..
stimulation.
- Used in diph………. and tetan…….. (toxoids), po…….. (whole inactivated virus).

Answer 26

Methods to improve immunogenicity

Adjuvants.
- Any substance that enhances the immune response to an antigen with which it is mixed.
- Alhydrogel – Al (OH)₃ used in human vaccines.
Induces Th2 response.
Antigen is adsorbed.
Reduces amount of antigen needed,
protects antigen from degradation,
creates an intracellular antigen
reservoir and enhances lymphocyte
stimulation.
- Used in diphtheria and tetanus (toxoids), polio (whole inactivated virus).

Question 27

Methods to improve immunogenicity.

Conjugation.
- Antibody response, particularly in young children can be improved by con………… the polys………… to proteins such as CRM…. to activate …. cells as well as … cells.
- Polys………….. are poor an………..
- Conjugation improves antige…….. of sub unit and enh……… response in inf…….
Hib poly ribitol phosphate, also P……
- Also used in men….. …… vaccine.

Answer 27

Methods to improve immunogenicity.

Conjugation.
- Antibody response, particularly in young children can be improved by conjugating the polysaccharide to proteins such as CRM197 to activate Th cells as well as B cells.
- Polysaccharides are poor antigens.
- Conjugation improves antigenicity of sub unit and enhances response in infants
Hib poly ribitol phosphate, also PCV.
- Also used in meningitis c vaccine.

Question 28

The UK vaccination Schedule

First vaccination given at 2months of age:
- Dip…………….
- Tet…………..
- Ace………… pertussis
- Inactivated polio vacc…………
- Haemophilus influ……………. type …..
Above are Pedi………..

• Pneu……………… vaccine (Prevenar)
• Rotav……..

Answer 28

The UK vaccination Schedule

First vaccination given at 2months of age:
- Diphtheria
- Tetanus
- Acellular pertussis
- Inactivated polio vaccine
- Haemophilus influenzae type b.
Above are Pediacel

• Pneumococcal vaccine (Prevenar)
• Rotavirus

Question 29

The UK vaccination schedule

Not given before the age of 2 months because there is an increased risk of adverse reactions and the immune system is unable to respond adequately before this time.
- The DT…/IP…/Hi… is repeated at .. and …. months.
- Men … is given with the 3 month vaccine (Neisvac … or meningtec)
Men C – Neisseria meningitidis C ……..polysaccharide with protein conj……….
- Rotavirus given at 3 months
- At four months PCV

Answer 29

The UK vaccination schedule
#Not given before the age of 2 months because there is an increased risk of adverse reactions and the immune system is unable to respond adequately before this time.
- The DTaP/IPV/Hib is repeated at 3 and 4 months.
- Men C is given with the 3 month vaccine (Neisvac C or meningtec)
Men C – Neisseria meningitidis C capsule polysaccharide with protein conjugate.
- Rotavirus given at 3 months
- At four months PCV

Question 30

The UK vaccination schedule

At 12 months children are given Hi.. and Men…

Me…….. M……… Rub…… . (MMR) is given between age of 1…. and 1.. months.
- All three viruses are live attenuated.

Not given earlier because of neut……….. by circu……… ma……. antibo….

A further dose of PC…. is also given at this stage

Influenza vaccine given between …… and …… years old

Answer 30

The UK vaccination schedule

At 12 months children are given Hib and MenC

Measles Mumps Rubella (MMR) is given between age of 12 and 15 months.
- All three viruses are live attenuated.

Not given earlier because of neutralisation by circulating maternal antibody.

A further dose of PCV is also given at this stage

Influenza vaccine given between 2 and 3 years old

Question 31

The UK vaccination schedule

3-5 years of age

• Diph…………../teta………./ace…. pertussis/inactivated polio (DTaP/IPV) bo……
• Boosts any dec……… imm…… and protects younger siblings by herd immunity.
• MMR second dose.
• Boo…… sustains Immunity……….. through the teenage years.

Answer 31

The UK vaccination schedule

3-5 years of age
Diphtheria/tetanus/acellular pertussis/inactivated polio (DTaP/IPV) booster.
Boosts any declining immunity and protects younger siblings by herd immunity.
MMR second dose.
Booster sustains immunity through the teenage years.

Question 32

The UK vaccination schedule

13-18 years of age

• Girls aged 12-13 years are given HP….. vaccine.
• Bo………. dose around 14 years old,
• Given T…./IP…., tet………., diph………, po……..
• Reduced level of diph…………. component.
• Men ….

Adults

• 65 and over given pneum………. and influenza.
• Over 70 years, shin………..

Answer 32

The UK vaccination schedule

13-18 years of age

• Girls aged 12-13 years are given HPV vaccine.
• Booster dose around 14 years old,
• Given Td/IPV, tetanus, diphtheria, polio.
• Reduced level of diphtheria component.
• Men C

Adults
- 65 and over given pneumococcal and influenza.
- Over 70 years, shingles.
6

Question 33

Non-routine childhood vaccinations

At birth
- Tube……….. for at risk groups

Hepatitis ….
- For babies whose mothers are Hep ……… positive

Answer 33

Non-routine childhood vaccinations

At birth
- Tuberculosis for at risk groups

Hepatitis B
- For babies whose mothers are Hep B positive

Question 34

Revised BCG programme

All infants living in areas where the incidence of TB is 40/100,000 or greater.
Infants whose parents or grandparents were born in a country with a TB incidence of 40/100,000 or higher.
Previously unvaccinated n…….. immi……… from high pre…….. countries for ……

Answer 34

Revised BCG programme

All infants living in areas where the incidence of TB is 40/100,000 or greater.
Infants whose parents or grandparents were born in a country with a TB incidence of 40/100,000 or higher.
Previously unvaccinated new immigrants from high prevalence countries for TB.

Question 35

Revised BCG programme

Children who would otherwise have been offered BCG through the sc……….’ programme will be screened for ri……. factors
- Tested and vac……… as appropriate.

BCG to be continued to be offered to those with occupational risk

• HC…..
• V…….. staff
• Pri………. staff etc.

Con………… of known cases.

Those intending to li……… or wo………. in ……… prevalence co……………..

Answer 35

Revised BCG programme

Children who would otherwise have been offered BCG through the schools’ programme will be screened for risk factors
- Tested and vaccinated as appropriate.

BCG to be continued to be offered to those with occupational risk

• HCW
• Vet staff
• Prison staff etc.

Contacts of known cases.

Those intending to live or work in high prevalence countries.

Question 36

Non-routine Vaccinations

Selected for particular at-risk groups.

Travel to places where diseases occur which are rare in the UK
- Hepatitis ………..

Occupation
- Exposure to path………. or infected individuals, risk of need…………. injury.

Susceptibility
-The elderly have higher more……….. from infl…………, pneu……………. on…………

Passive immunity via specific immunoglobulins after exposure in non-im………. individuals
- Va……….. zoster

Answer 36

Non-routine Vaccinations

Selected for particular at-risk groups.

Travel to places where diseases occur which are rare in the UK
- Hepatitis A

Occupation
- Exposure to pathogens or infected individuals, risk of needlestick injury.

Susceptibility
-The elderly have higher morbidity from influenza, pneumococcal pneumonia.

Passive immunity via specific immunoglobulins after exposure in non-immune individuals
- Varicella zoster