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B3.0 > Evolutionary Dynamics of Infectious Disease > Flashcards

Evolutionary Dynamics of Infectious Disease Flashcards

1
Q

SIR

A
  • measles, mumps, rubella
  • childhood diseases
  • we can vaccinate (durable protection)
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2
Q

SI

A
  • HIV
  • potential vaccination; don’t want to replicate natural immunity (because of stable dynamic)
  • logistic growth that reaches equilibrium
  • evades immune clearance
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3
Q

SIRS

A
  • flu, SARS-CoV-2
  • clearance and re-infection
  • antigenic diversity
  • model expansion (strains, behavioural differences [sequential dominance, e.g flu])
  • potential for short term vaccines against circulating strains (partial prevention)
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4
Q

Antigenic diversity

A
  • changes antigens through which we recognise and mount immunity
  • R host becomes S
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5
Q

Dominant targets of immunity

A

Determinant epitopes

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6
Q

Invariant epitopes

A

SIR

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7
Q

Measles vs flu

A
  • Constrained -> variable continuum
  • multi-locus entities @ level of antigenic sites
  • similar viruses: HA
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8
Q

HA

A
  • surfaces to facilitate viral attachment
  • RBS to engage relevant receptor
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9
Q

Measles

A
  • epitope central of RBS (Arg333, Asp505)
  • under v. strong immune selection
  • escape = difficult due to high structural constraint
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10
Q

Flu RBS

A
  • protected in crater by overhanging crags of HA loop epitopes
  • binds to sialic acid residues in host cell membrane
  • released from structural constrains = change!
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11
Q

You can categorise an array of genes by specific functions

A
  1. Regulatory
  2. Metabolic
  3. Structural
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12
Q

Functions must separately encode

A

1) transmission
2) virulence
3) antigenic determinants

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13
Q

SIR models assume

A
  • conservation of dominant epitopes
  • same virulence
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14
Q

What if there is a different in transmissibility under SIR

A
  • creates different “I” compartments
  • higher transmissibility leads to higher R0 (R0 = BD)
  • competitive exclusion
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15
Q

What is the strains are equally transmissible, but vary in virulence?

A
  • α (pathogen-induced mortality, from I compartment) has an inverse relationship with D
  • virulence reduced competitiveness
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16
Q

Variability in virulence: D =

A

1 / (σ + α); where σ = I->R

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17
Q

T/V Tradeoff

A
  • factors can affect both (e.g. viral load)
  • B α V
  • D α -V
  • R0 may be maximised at intermediate virulence
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18
Q

European rabbit in Australia

A
  • 1859: 24x rabbits introduced
  • 1866: 14,253 rabbits shot
  • 1950: Myxoma release as vertebrate biocontrol
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19
Q

Grade I myxoma

A
  • fully virulent
  • mortality: 10-15 days
  • 12% fleas infective
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20
Q

Grade 3

A
  • intermediate virulence
  • mortality: 17-44 days
  • 42% fleas infective
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21
Q

Grade 5

A
  • attenuated
  • no mortality
  • 8% fleas
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22
Q

1952-1955 myxoma distribution

A
  • 1: 12%
  • 3: 52%
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23
Q

1975-1981 myxoma distribution

A
  • 1: 1%
  • 3: 68%
24
Q

Can imperfect vaccines increase virulence?

A
  • protect against severe outcomes (still good!)
  • don’t necessarily stop infection; decouples intrinsic virulence + effect on host
25
Q

Vaccinating a fraction of the population…

A
  • alters effect on host, but not transmission
  • point of optimal virulence is higher, since prolonging lifespans &laquo_space;α
  • removes evolutionary pressure
  • severe strains higher frequency
  • need total vaccination
  • accessibility
26
Q

Marek’s disease

A
  • highly contagious lymphoproliferative disease of poultry
  • caused by MDV
  • chronic
  • annual loss > $1bill
  • overcome vaccines
  • independent virulence paths in Eurasia and NA
27
Q

Marek’s disease live vaccine

A
  • in ovo: 18 day old embryo
  • hatchlings
  • hard to prove > R arises from vaccination advent
28
Q

MDV

A

oncogenic herpesvirus

29
Q

Absence of competition

A
  • promotes co-existence
  • cross-immunity = γ
30
Q

When γ = 0,

A

Strains function independently

31
Q

To what extent can you get coexistence, depending on the level of immunological interference?

A
  • range!
  • total coexistence -> total competitive exclusion
  • region of coexistence broadens as γ -> 0
  • niche differentiation along axes hypervolume
  • partitioning and segregation
32
Q

Escaping γ

A
  • How can human-associated B. parapertussis and B. pertussis coexist when vaccinating against B. pert protects you against B. para?
  • How could B. para invade when B. pert was endemic?
33
Q

Bordetellae

A
  • came from B. bronchiseptica in pigs (persistent commensal)
  • O antigen, outer core, inner core, Lipid A
34
Q

B. pert

A
  • 5-10,000ya
  • Neolithic revolution
35
Q

B. para

A
  • acute immunising respiratory pathogens
  • genomic rearrangement and reduction
  • more recently emerged (500ya)
  • evolutionarily independent lineage (re. phylogeny)
36
Q

O- antigen

A
  • part of LPS
  • structural preservation and membrane transport
  • rough/smooth: P/A
  • protects B. para from γ in Mus
  • crucial for establishment; facilitated coexistence and co-circulation
37
Q

O antigen phylogeny

A
  • B. pertussis: no
  • B. para: retained
  • B. broncho: retained
38
Q

Deleting O antigen from B. para

A
  • naive mice: no change
  • B. pertussis immunised mice: no colonisation (makes it immune-susceptible)
39
Q

B. para vaccine

A
  • prevent severe disease
  • not lifelong
40
Q

Streptococcus pneumoniae

A
  • Gram +ve
  • nasopharyngeal
  • invasive infections: pneumonia, meningitis, sepsis
  • > 800,000 deaths < 5yo (esp. SSA)
  • > 100 capsule types (minimises γ: differentiation of antigenic targets)
  • ~15 pathogenic
  • natural immunity: no R, prevents α
41
Q

Pneumococcal conjugate vaccines:

A
  • polysaccharide: protein
  • PCV7
  • PCV13
42
Q

“From the POV of the adaptive immune system,

A

each S. pneumoniae serotype represents a distinct organism”

43
Q

cps locus

A
  • polysaccharide biosynthetic enzymes
  • associated w virulence
  • targeted by vaccines
44
Q

Serum therapy?

A
  • anti-capsular horse serum
  • type-specific vaccines
  • little evidence from natural immunity
45
Q

Differentiation of cps locus:

A
  • high
  • flippase assembly system
  • v high diversity permits coexistence
46
Q

Kilifi, Kenya methodology

A
  • 2840 children (3-59m): nasopharyngeal swabs
  • 1868 (66%) +ve @ baseline
  • reswabbed: 1, 2, 4, 8, 16, 30, 60, 90 days
  • until two consecutive swabs found -ve for baseline serotype (no pneu/ a different type
47
Q

Kilifi, Kenya measuring

A
  • R0 (B, D)
  • weak competition and widespread coexistence
  • no optimisation of single strain; standing diversity
48
Q

Salmonella typhimurium

A
  • direct interactions mediate competition; classical ecology
  • recruits immune system to alter competitive landscape via sophisticated strategy
  • respires ethanolamine (abundant simple substrate carbon source released by host tissues but useless to competitors)
  • growth advantage
  • requires tetrathionate (respiratory EA)
49
Q

Salmonella typhimurium pathology

A
  • invasion: T3SS
  • epithelium -> macrophages -> inflammation!
  • neutrophils: secrete ROS; thiosulphate oxidation -> tetrathionate
50
Q

Lineage structure in bacterial pops

A

sequence clusters associate w antigenic serotype

51
Q

Resource competition

A

Discrete metabolic types, drives diversification

52
Q

Metabolic analysis of pneumococcal genomes

A
  • 616 from Massachusetts
  • 890 loci (+ transport)
  • allelic diversity: Genome Comparator
  • discrete, distinct barcodes constitute metabolic loci, and associate w a particular serotype
53
Q

PCVs can alter the genome profile of non-vaccine serotypes

A
  • vaccinating against particular serotypes in a modular pop
  • immune selection on capsule
  • increased T and V?
  • ## 40% increase in Pilus Type II in 19A since PCV7; elements rearrange to find optimal structure
54
Q

Modular reorganisation investigation

A
  • machine learning analysis
  • immune selection on groEL HSP
  • elicits Ab
    1) identify which serotype each isolate belongs to, via barcode
    2) rank genotype informativeness of isolates by serotype
    3) score = gene predictivity
55
Q

groEL

A
  • operation is critical in protein folding
  • epistatic
  • potential vaccine candidate?

B3.0 (26 decks)

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