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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
Vaccinating a fraction of the population…
- alters effect on host, but not transmission - point of optimal virulence is higher, since prolonging lifespans << α - removes evolutionary pressure - severe strains higher frequency - need total vaccination - accessibility
26
Marek’s disease
- highly contagious lymphoproliferative disease of poultry - caused by MDV - chronic - annual loss > $1bill - overcome vaccines - independent virulence paths in Eurasia and NA
27
Marek’s disease live vaccine
- in ovo: 18 day old embryo - hatchlings - hard to prove > R arises from vaccination advent
28
MDV
oncogenic herpesvirus
29
Absence of competition
- promotes co-existence - cross-immunity = γ
30
When γ = 0,
Strains function independently
31
To what extent can you get coexistence, depending on the level of immunological interference?
- range! - total coexistence -> total competitive exclusion - region of coexistence broadens as γ -> 0 - niche differentiation along axes hypervolume - partitioning and segregation
32
Escaping γ
- 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
Bordetellae
- came from B. bronchiseptica in pigs (persistent commensal) - O antigen, outer core, inner core, Lipid A
34
B. pert
- 5-10,000ya - Neolithic revolution
35
B. para
- acute immunising respiratory pathogens - genomic rearrangement and reduction - more recently emerged (500ya) - evolutionarily independent lineage (re. phylogeny)
36
O- antigen
- 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
O antigen phylogeny
- B. pertussis: no - B. para: retained - B. broncho: retained
38
Deleting O antigen from B. para
- naive mice: no change - B. pertussis immunised mice: no colonisation (makes it immune-susceptible)
39
B. para vaccine
- prevent severe disease - not lifelong
40
Streptococcus pneumoniae
- 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
Pneumococcal conjugate vaccines:
- polysaccharide: protein - PCV7 - PCV13
42
“From the POV of the adaptive immune system,
each S. pneumoniae serotype represents a distinct organism”
43
cps locus
- polysaccharide biosynthetic enzymes - associated w virulence - targeted by vaccines
44
Serum therapy?
- anti-capsular horse serum - type-specific vaccines - little evidence from natural immunity
45
Differentiation of cps locus:
- high - flippase assembly system - v high diversity permits coexistence
46
Kilifi, Kenya methodology
- 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
Kilifi, Kenya measuring
- R0 (B, D) - weak competition and widespread coexistence - no optimisation of single strain; standing diversity
48
Salmonella typhimurium
- 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
Salmonella typhimurium pathology
- invasion: T3SS - epithelium -> macrophages -> inflammation! - neutrophils: secrete ROS; thiosulphate oxidation -> tetrathionate
50
Lineage structure in bacterial pops
sequence clusters associate w antigenic serotype
51
Resource competition
Discrete metabolic types, drives diversification
52
Metabolic analysis of pneumococcal genomes
- 616 from Massachusetts - 890 loci (+ transport) - allelic diversity: Genome Comparator - discrete, distinct barcodes constitute metabolic loci, and associate w a particular serotype
53
PCVs can alter the genome profile of non-vaccine serotypes
- 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
Modular reorganisation investigation
- 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
groEL
- operation is critical in protein folding - epistatic - potential vaccine candidate?

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