Lecture 15 (9A) - Vaccination Flashcards
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
mutations/recombinations
Vaccination gives a bigger dip than
antibiotics
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
process
- 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)
PASSIVE IMMUNIZATION DOES NOT GIVE LONG-LASTING PROTECTION
Poliomyelitis
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 (^MMR) • 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
but
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
Adjuvants
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
- virus - a specific gene is isolated from the pathogen
- the gene is placed in a bacterial plasmid vector (bacterial DNA acts as an adjuvant via TLR9)
- cytokines?
(inflammation - good immune response)
- cytokines?
- the plasmid is injected into the muscle of a recipient
• DC takes up plasmid, expressed gene and acts as adjuvant –> DC activated - 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
