Vaccination Flashcards
(36 cards)
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…………..
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
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.
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.
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………
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.
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!
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!
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.
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.
Development of vaccination
Created vaccines for anthrax and rabies. 1798 sm.............. 1885 ra............. 1897 Pl............. 1923 D................. 1926 p................ 1927 BC........., tub............. 1927 tet.........,
Development of vaccination
Created vaccines for anthrax and rabies. 1798 smallpox 1885 rabies 1897 Plague 1923 Diphtheria 1926 pertussis 1927 BCG, tuberculosis 1927 tetanus,
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………
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.
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.
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.
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.
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.
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………).
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).
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……….
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.
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.
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.
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.
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.
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….).
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).
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.
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.
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.
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.
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.
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.
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.
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.
Traditional vaccines
Toxoid
- Ina…………… form of a t…….. produced by pa…………… ………………:
Dip……….. and Te………… – very good.
Traditional vaccines
Toxoid
- Inactivated form of a toxin produced by pathogenic bacteria:
Diphtheria and Tetanus – very good.
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..
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.
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…….
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.
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.
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.
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.
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.
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.
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.
