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Aerosols and Aerobiology
Chad J
...
D
...
communicable
(natural) infection
• disease (model) development
– microbial
susceptibility/infectivity
– ‘quantal’ biological
response
– comparative
pathogenesis/size modality

An exemplar of natural airborne infection:
communicable transmission of M
...
tb?
1e+6
sneeze
cough

8e+5
number of particles

• transmission of M
...


• host
– innate susceptibility
– the nature and number of
interactions with ‘producers’
– P is dynamic (too much so
to model)

• pathogen
– innate microbial fitness
– source (from host)
– particle aging/duration while
in transit
– dynamic size while in transit

M
...
0e+7
1
...
0e+5
-14d

1
...
0e+3
1
...
0e+1

+7d +14d +21d +28d +35d +42d +49d +56d +63d
postexposure

•
•

1
...
0e-1
1
...
3

0
...
0

5
...
immune evasion mechanisms employed by some
pathogens
• Modeling aerosol-acquired disease in appropriate animal species
• differential pathogenesis from exposure to distinct particle distributions

modeling airborne-acquired infection
source generation
airborne

droplet nuclei

pretreatment
generation

viability

delivery

Y
...
coli
Bacillus globigii, vegetative
Bacilus globigii, spore
Bacillus smegatis
Strepococcus hemolyticus
Strepococcus viridans
Staphylococcus aureus

Bacteriophage
Influenza virus

Mycobacterium tuberculosis

runs

relative
vunerability*

6
5
9
4
13
13
5
-

1
...
68
0
...
52
0
...
93
1
...
14
1
...
84

Sample Efficiencies of Biological Threat Agents in Aerosol
Impact of Viability upon Estimated Aerosol Concentration

1e-5

spray factor

1e-6

1e-7

1e-8

1e-9
Y
...
anthracis

B
...
mallei v
...
pseudomallei
1e-4
BP wild-type
(saprophyte)

1e-5

spray factor

1e-6

BM wild-type
(obligate)

1e-7

1e-8

1e-9

1e-10

1e-11
ATCC23344C

10266C

Aerosol biophysical characteristics
• Concentration
– a function of the number and size of particles
generated

• Particles characterized by:
– geometric and aerodynamic size
– shape, density and surface area
– electrical charge / conductance
– number and strength of interactions
– between other particles or cloud components

Biological Aerosol Size
•

Use equivalent diameter that derives from particle property relevant to
bioaerosol exposures
– Mechanism of deposition
– Particle size

•

Aerodynamic diameter: diameter of a unit-density sphere having the
same gravitational settling velocity as the particle being measured
Irregular Shape

Varying Densities

Equivalent Diameter

 = 1 g/cm3

 = 4 g/cm3

 = 9 g/cm3

 = 1 g/cm3

d=?

d = 3 m

d = 2 m

d = 6 m

particle generation methods for
infectious agents
• Standard generation
methods employed
for generating larger
particle pathogencontaining aerosols
that retain viability
– spinning top aerosol
generator
– compared to
standard industrial
nebulizer and
resulting distribution

1e+5

SPG - number
SPG - mass
LPG - number
LPG - mass

1e+4
1e+3
1e+2
1e+1
1e+0
1e-1
1e-2
1e-3
1e-4
1e-5
0

2

4

6

8

10

particle diameter (m)

12

14

Source-Based Particle Distribution
10
MMAD,1
...
4

10

8

6

2

1

10

particle size ()

>25

10
...
0

5
...
0-5
...
5-1
...
1

0
...
5

dM/dlogDp

1

Initial Deposition and Clearance
• Particle deposition defines the organs/tissues
with first contact
• Clearance defines the duration the body is in
contact with the agent
– bulk clearance
– mucociliary clearance
– alveolar clearance

• Ultimately both play major roles in the agents
pathology and pathogenesis

Human deposition patterns

From ARL, PSU, 2007

From Edwards et al
...
0

URT
TB
LRT
TOTAL

deposition fraction

0
...
6

0
...
2

0
...
01

0
...
g
...
g
...
Epifluorescent ricin
particles localized to the olfactory
epithelium in the turbinates (A; 40X)
whereas particles are localized to all
levels of the olfactory epithelium (B;
100X)
...
The lungs of the
mouse exposed to the nonrespirable
aerosol (A) shows no significant lesions
...


from Roy et al
...
, Experiment of mass aerogenic vaccination against anthrax (1959)
et al
...
, Simultaneous aerosol immunization of monkeys with live tularemia and live VEE vaccines (1964)
4 Muromstev et al
...
, Aerosol vaccination with tetanus toxoid (1966)
6 Cohn et al
...
, Humoral immunity to aerosolized SEB vaccinated with SEB toxoid-containing microspheres (1995)
8 Fernadez de Castro et al
...
, Rubella virus immunization in pre-school children via the respiratory tract (1974)
10Sepulveda-Amor, J
...
, A randomized trial demonstrating successful boosting reaponses following simultaneous
aerosols of measles and rubella (MR) vaccines in school age children (2002)
2 Eigelsbach

Early Abandonment of the Effort
lack of advanced technology paired with suboptimal reagents

• early crude vaccines were reactogenic
• mainly live attenuated or toxoids used
– adverse events  over injection
– no identified mucosal adjuvants

• Individual inhalation devices largely
unavailable
• failure to identify ‘dual immunity’ concept
• troop compliance
– was ‘cold chain’ logistical support up to the task?

Alternative Delivery: Inhalation
recent trends in biopharmaceuticals
• Therapeutics1
–
–
–
–
–
–
–
–

calcitonin (osteoporosis)
teriparatide (osteoporosis)
rGH (GH disorder)
interferon  (hepatitis C)
heparin (deep-vein thrombosis)
insulin (diabetes)
extendin-4 (diabetes)
1-antitrypsin (congenital emphysema)

• Vaccines
– (EZ) measles
– influenza

1Minter,

B
...
, Emerging Delivery Systems for Biopharmaceuticals, Decision Resources, 2001

Aerosol Vaccination for Measles and Rubella 1
Acute Adverse Events (% incidence)
N
Reactions

(307)
SC

(225)
AEROSOL

P

Fever
Rhinitis
Cough
joint pain
Diarrhea

6
...
3
17
...
9
1
...
6
0
...
4
0
0

0
...
02
0
...
0001
0
...
7
55
...
5

98
...
9
159
...
04
0
...
4

PV seropositivity
Seroconversion

92
...
4

99
...
8

0
...
001

Measles

Rubella

1Data

from Sepulveda-Amor, J
...
, 2002

Micro- and Nano-particle Vaccine Delivery Systems

Monolithic micro- and
nano-particles that are ideal
for encapsulation of
subunit or inactivated
vaccine

Reservoir or ‘balloon’
microcapsules designed
for live vaccine or active
protein

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