Lecture 5: BACTERIAL EVOLUTION UNDER VACCINE PRESSURE Flashcards
BACTERIA VS VIRUS.
*Bacteria are ‘free-living’ and uni-cellular
-Different in size
-Difference in composition –a virus is NOT a cell and is NOT free-living
how are BACTERIA RELEVANT TO HUMAN OR ANIMAL HEALTH
Commensal bacteria, bacteria in the food chain, infection-causing bacteria
CARRIAGE VERSUS INFECTION
Being colonized by bacteria is a normal, healthy and helpful state
-this Includescarriage of potentially harmful bacteria (Staphylococcus aureus
what are BACTERIA’S COMPOSITIOns?
Vaccines will induce immune responses that target these components
ØEspecially those outside of the bacteria –accessible to antibodies
ØCapsule: polysaccharide layer outside the cell envelope:
-Encapsulated bacterial
-Virulence factor: adhesion, resistance to host defences (Protect against phagocytosis), intracellular survival
-S. pneumoniae, E. coli, Klebsiella, Neisseria…
-Often good targets for vaccines
ØCell wall
CELL WALL: GRAM NEGATIVE AND POSITIVE
-No LPS: (Gram-positive bacteria)
BifidobacteriumS. Aureus
TB
S. pneumoniae
Anthrax
Clostridium
Listeria
*With LPS: (Gram-negative)
Acetic acid bacteria
Zymomonas(Tequila)
E. coli
Salmonella
Neisseria
Bordetella
Vibrio cholera
Pseudomonas
Campylobacter
what are the functions of immunity?
protection
what are the different types of immune responses?
innate (at birth)
-inflammation and healing
adaptive (develops and declines with age)
-Humoral (antibodies)
-cellular (helper T cells (CD4) and cytotoxic T cells (CD8))
IMMUNOLOGY & VACCINOLOGY
ØBalance danger signal / safety
ØInduction of immune responses against relevant parts of the pathogen (functions that can disrupt the target pathogen)
ØInduction of immune response in the target population (babies, elderly…
VACCINE PRESSURE ON BACTERIA
Vaccines induce antibodies with different functions
ØPrevent colonization
ØBlock adhesion to cells / mucosa
ØBlock entry into cells
ØPromote phagocytosis
ØInduce complement activation –>bacterial death
Vaccines induce T cells
ØHelp B cells to produce more/stronger antibodies
ØKill infected cells
what are key characteristics of bacteria
bacteria have evolved for 3 billions of years to adapt
ØShort generation times and large populations sizes
ØGenome modification (mutations in DNA) occur constantly
ØAcquisition of genetic material (plasmids)
ØPhase variation (Single sequence repeats
ØAntibodies do not bind anymore
ØLoss of antibody functions
*Same mechanism for T cell targets
*Is this natural selection (survival) or artificial selection (driven by man)?
why would bacteria change their genes?
*So bacteria change their genes
*Genes code for different proteins
ØChange in proteins on the surface->antibodies do not recognize their target
ØChange in enzymes in the bacteria->change in the sugar composition on capsule
ØAntibodies do not bind anymore
ØLossofantibodyfunctions
*Same mechanism for T cell targets
*Is this natural selection (survival) or artificial selection (driven by man)
what is N.MENINGITIDIS
*Causes meningitis and septicemia, can kill in less than 4 hours
*Capsule composition->serotype
Ø13serotypes
ØA, B, C, W, Y cause disease in humans
ØVaccines against A,C, W and Y based on CPS (CPS is the antibody target)
ØEachvaccine is SPECIFIC for its capsule
Ø=doesnotprotectagainsttheotherones
ØVaccination of babies/ teens in several countries depending on the serotypes prevalent in that countries
SEROTYPE REPLACEMENT: S.PNEUMONIAE
Capsule composition-> serotype
Ø1.6 million deaths/year -children <5 years
Ø >100 serotypes, almost all can cause disease in humans (difference in virulence)
ØVaccines based on capsular polysaccharide (CPS)
Ø Each vaccine is SPECIFIC for its capsule = does not protect against the other ones
ØVaccine components against each serotype mixed into different vaccine compositions
- Pneumovax23 (PPV23): 23 capsules mixed –not very immunogenic in children
- 7-valent conjugate vaccine(PCV7) –the 7 most prevalent, most expensive, very immunogenic in children
what is whooping cough?
*Disease caused by Bordetella pertussis
*HIGHLY contagious infection of the lungs,can be severe and even deadly in babies
*Vaccinesdeveloped along time ago
ØWhole cell vaccine, efficacious but reactogenic
ØAcellular vaccine, less reactogenic
*Problem: whooping cough cases have been increasing in several (rich) countries since use of Acellular vaccine
problem which accellular vaccines
Because Acellular vaccine does NOT prevent carriage it means there is still transmission
*Bacteria has time to evolve and can DROP pertactin, and change FIM expression
