Lecture 15 (9A) - Vaccination Flashcards Preview

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Flashcards in Lecture 15 (9A) - Vaccination Deck (28):

Edward Jenner

• developed the first vaccine - against smallpox
• used a related virus (vaccinia) from cows to generate an immune response which cross-reacted against smallpox
• since 1980 smallpox has been completely eradicated from the world (it's possible to completely eradicate a dsease(

• cow - vacca

• cowpox and smallpox close enough that if given cowpox don't get smallpox


There are no vaccines for some diseases because

they hide from the immune system
- immune can't get it so (immune) goes away a bit


Vaccines may not work because of



Vaccination gives a bigger dip than



Vaccination is the

success story of medicine
• the principle reason why immunology became important


Features of an effective vaccine

• safety - must not itself cause illness or death
• protection - must protect against exposure to the pathogen
• longevity - should give long-lasting protection
• neutralizing antibodies - must be induced to protect against pathogens such as polio, and many toxins and venoms
• protective T cells - must be induced to protect against pathogens such as TB
• practicality - cheap to produce and easy to administer


Herd immunity

• if people are in a place, next to each other = in contact
• 1 person gets something --> many/most get it
• don't need to vaccinate everybody (eg 80%)
• enough people vaccinated = disease doesn't spread, no outbreak/epidemic

when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity


Types of vaccination

• active immunization
--> moder vaccines
• passive immunization


Vaccination is

active immunization, not passive


Active immunization

• inactivated vaccines (eg heat-treated)
• attenuated vaccines (a weaker strain eg get antibodies from moms breast milk = babies immune system fights weaker pathogens)

--> modern vaccines


Passive immunization

• receiving antibodies
• transfer or maternal antibodies from mother to baby

• passive = receiving antibodies
short term protection
not changing immune system - not vaccination
vaccination keeps safe with longevity


Passive imminization - receiving antibodies

• inject killed pathogen
• 10 days later take blood
• serum from blood (including neutralizing antibodies)
• give serum to another mouse (transfer of antibodies)
• challenge with live pathogen = animal survives


Passive immunization

• often given to counteract insect/animal venoms (eg spider or snake)
• usually horse serum is used
• there are problems associated with this type of immunization
- the immunization effect lasts for as long as the antibody remains active - a few months at the most
- the patient makes an immune response against the serum (can cause serum sickness)




polio - infantile paralysis
• the child-killer of the 1940-1950s
• Jonas Salk (and slightly later Albert Sabin) both developed an effective vaccine to polio


Jonas Salk's polio vaccination

inactivated vaccine
• the polio virus "marinated" in formalin (pickled)
• the virus is unable to replicate (deactivated)
• the vaccine generates good humoral immunity
• no change of disease (but often adverse side effects)


Albert Sabin's polio vaccination

Attenuated vaccine
• a live weakened polio virus was generated (from guinea pigs)
• the virus can replicate but doesn't cause disease
• the vaccine generates both humoral and cell-mediated immunity
• occasional polio in vaccinated patients


Salk v Sabin

• Salk = injection
• Sabin = sugar lump

• Salk - pickled polio (killed)
• Sabin - didn't kill it but attenuated - grew in guinea pigs, got less virulent = doesn't cause disease but get response

• polio is in gut (water)
sugar lump goes and acts in gut, replicates inside you, better immune response

• Salk --> Sabin --> Salk
• Salk safer, people get injection, polio decreased
• Salk infected with no symptoms but can pass on (no symptoms but have polio)
• Sabin clears because polio in sugar in same path (to gut), better gut response, rids polio


Inactivated vaccine

DC has MHC-I and MHC-II inside
• formalin treated viral particles go in, don't cause infection
• present the viral particles on MHC-II

• viral peptide on MHC-II which generates a good CD4+ T cell response --> good antibody production via TH2 CD4+ T cells

(no good on CD8)


Attenuated vaccine

• attenuated viral particles do infect cell
• to nucleus, make viral proteins
• display viral proteins on surface in both MHC-I and MHC-II
• viral peptide on MHC-II and MHC-I which generates a good CD4+ and CD8+ T cell response, hence good antibody production and T cell mediated cytotoxicity


Inactivated vaccines

require neutralizing antibodies
• diptheria
• whooping cough
• tetanus
(^3 = DPT)
• polio (Salk)
• cholera
• influenza
• plague
• rabies (now attenuated)


Attenuated vaccines

require neutralizing antibodies and a cell-mediated response
• measles
• mumps
• rubella
• polio (oral - Sabin)
• chicken pox
• tuberculosis (BCG)
• influenza
• yellow fever
• rabies


Recombinant peptide vaccines

eg Hepatitis B
• this method does NOT use the whole pathogen - reducing risk of side effects

• a specific gene is removed from the virus/pathogen
• gene is added to a culture of yeast
• a single purified viral protein is used for the vaccine
• mixed with adjuvant
--> vaccine

genes cut out, put into vector, get genes to make proteins and use proteins to make vaccine
• how does it know the gene is from protein (of pathogen?)
• adjuvant - protein + pathogen product that tricks immune system into thinking its part of a pathogen
• adjuvant tricks the DC (onto MHC- mostly II) but no B7 or CD40 (no costimulatory molcules)
- adjuvant tricks DC into thinking pathogenic infection


The use of adjuvants to make a vaccine immunogenic

adjuvants trick the immune system into thinking that there is an infection

• most purified antigens are not strongly immunogenic
eg tetanus toxoid not immunogenic
tetauns toxoid + aluminum salts (an adjuvant) = immunogenic (elicits antibodies)

purified viral protein to DC
• no adjuvant = only MHC on DC surface
• with adjuvant (+ cytokines like IL-12) = costimulatory as well (B7, CD40)
==> activates naive T cells



trick the immune system into thinking that there's an infection
• bias toward TH2 antibody response
• stimulate mucosal immunity (eg using pertussis toxin or cholera toxin)
• bias toward TH1 cell-mediated responses (eg using IL-12)
• activate (B7 etc) dendritic cells (and other APC)


Considerations for vaccine design

whole pathogens or recombinant protein?
- live attenuated or inactivated vaccine
-which protein to use? does it elicit protective immunity?

does the vaccine require an adjuvant?
-which adjuvant (does the adjuvant promote the correct type of immunity ie cell-mediated or antibody)
- which vaccination route? mucosal (like most infections)? or injection (unlike most infections)

are booster vaccinations required?
can the vaccine be target to certain APC?

safety + cost


Modern vaccines - DNA vaccines

1. virus - a specific gene is isolated from the pathogen
2. the gene is placed in a bacterial plasmid vector (bacterial DNA acts as an adjuvant via TLR9)
3. + cytokines?
(inflammation - good immune response)
4. the plasmid is injected into the muscle of a recipient
• DC takes up plasmid, expressed gene and acts as adjuvant --> DC activated
5. viral challenge
--> animal is protected

in trials for malaria and HIV


The future - therapeutic vaccines

an animal is already infected and cannot clear the infection (eg herpes simplex-2 or certain papilloma viruses)
• the sick animal is vaccinated to boost the immune response to the infection
(boosts w/ longevity - vaccine)
== the animal can now clear the infection


Cure vs vaccine

cure acts directly on the pathogen
vaccines deal with the immune system