Vaccines
in
Immunobiology
and
Medicine
Folder title: VaccinesNoTP
Updated: December 04, 2012
Immunology in Human and
Animal Health and Disease
Why do we want to know about Immunology?
What does it tells us about ourselves and
about biology?
What can it do for us?
As a tool in biomedical research?
As a diagnostic and therapeutic modality in clinical and
veterinary medicine?
What can it do to us, as a source of pathology?
Immunology in Human and Animal
Health and Disease
What can we
make it do
for us?
KEY FEATURES OF SPECIFIC ADAPTIVE
IMMUNITY IN HISTORY
Freedom from Plague after Surviving
First Exposure
Immunity Exists
Susceptibility to Other Diseases
Even After Surviving Plague
Immunity is Specific
Deliberately Induce Small-pox to
Protect Against Later Exposure
Immunity has Memory
Induce Non-pathogenic Cow-pox to Protect
Against Virulent Small-pox (Vaccination)
Resistance to Chicken Cholera
after Surviving Exposure to Weakened Chicken
Cholera Bacilli (Attenuated Vaccines)
Related Antigens
are Cross-Reactive
Antigens can be
separated from
pathogenic features
Why Not:
1. Deliberately expose people to the disease organism
under controlled conditions?
2. Expose people to the attenuated non-pathogenic
organism?
3. Expose people to a related organism that is like the
pathogenic one but doesn’t cause disease? (e.g.
vaccinia virus from Cox-pox)
4. Get antigens from the pathogenic organism separate
from disease-causing properties and use those on
people ?
Vaccines in Human
and Veterinary Medicine
What have they done for us?
What do we have now?
How do they work?
What don't we have?
Why not?
How can we get what we need?
How can we improve their immunogenicity?
Can vaccines for millions of healthy persons cause problems ?
Can we make them faster in response to changes in pathogens?
Oakwood Cemetery
10-Nov-96
Filename: OakSec29.doc
Name
Robbie Bonta
Katherine T. Bonta
Frank M. Bonta
Helen A. Plumb
Laura J. Benner
Samuel
George L. Bonta
H. Benner
Blank
Frankie L. Curtis
Frances B. Curtis
Nathan L. Curtis
Roger L. Jones
Mary C. Jones
Fannie Lathrop
Rachel Amelia Cody
Burials
Born
1868
1864
1845
1853
1850
1873
1848
1876
Unk
1864
1844
1836
1872
1875
1871
1840
Died
1875
1945
1939
1886
1876
1874
1922
1888
Unk
1875
1932
1922
1951
19??
1879
1840
Unk
Missing
Unk
Unknown
1800
George Chapman Lathrop
Unknown
Unk
George Nelson
1847
George Chapman
Average Age:
Notes: 10 died aged 6 wks to 33 yrs.
Age in
Years
7
81
94
33
25
1.5
74
12
Unk
11
88
86
79
Section 29
Survey by Tom Fondy
Remarks
March 22, 1875, Age 6 yrs & 8 mos.; Son of Samuel
Jan. 20, 1886; Wife of Frank M. Bonta
Died Feb. 9, 1876; Wife of Frank M. Bonta
Son of F & L Bonta; Aged 1 yr & 7 mos
Born Feb. 9, 1876 (See Laura S. Benner)
Next to H. Benner; Tombstone is Blank
Born Sept. 22, 1864; Died Feb. 14, 1875
(Also a child. Should be blue)
8
0.1
Unk
Died Dec. 27, 1879; Age 8 yrs, 8 mos, 3 dys
d. August 8, 1840; Age 6 wks and 4 dys;
Daughter of Narcissa & Niel? Cody
Faded (Could be Narcissa or Niel Cody)
Unk
1883
1811
Unk
1849
Unk
83
1898
87
Unk
Tombstone Toppled
2
Son of Benjamin & Permela Lathrop
4
Aged 3 yrs, 10 mos, 16 dys
43.1
50% of Identifiable Dates! 8 died aged 74 to 94.
See Verses by TPFondy at http://tpfondy.mysite.syr.edu/
Song of the Oakwood Children
Verses and Self-running Presentation
19 Identifiable persons with dates.
8 are children 0 to 12 years of age!
Song of the Oakwood Children
See Verses by TPFondy at
http://tpfondy.mysite.syr.edu/
Verses and Self-running Presentation
BIO 477 Fall 1999
Filename: Oakwood.xls
Oakwood Cemetery Data
Updated: December 5, 1999
Young
S ection
Mean
Median
S pan
Children Adults
Prior 1900
0 to 15 16 to 40
Abrams, Marshall
46
Not given Not Given 0 to 103
17%
13%
Arace,Jennifer A
Not Given
46.7
47.5
1 to 89
25%
15%
Arcuri, Phil
14
63.15
64.5
25 to 87
0%
20%
Azeez,Mohamed C
50*
59.3
78.5
4 to 109
19%
6%
Berard, Eric
29
45.1
48
2 to 74
10%
25%
Boyer, James
20A
Not given Not Given Not Given
?
?
Broderick,Lori
48
48.1
59.5
1 to 89
25%
10%
Brusgul,Anthony M
10
56.4
71
1 to 94
15%
20%
Burpee,Stacey D
9
67.5
75.5
1 to 94
5%
5%
Clark,Sharon K
48W*
60.2
56
20 to 102
0%
5%
Covington,Ari-Anna M
46*
55.6
71
1 to 96
20%
5%
Darling,Jennifer S
35*
47.2
57
1 to 97
28%
17%
Di Re,Vicky
47
41
51.5
0 to 85
40%
5%
Domville,Shelley L
7
51.9
52.5
0 to 84
10%
10%
Douangnouanexay,Ladda
58*
59.9
69.5
6 to 94
5%
11%
Fernandez,Jason E
15
60.5
66
9 to 83
5%
10%
Fogu,Brian S
See Julie Sherman
Gengo,Jessica
46*
55.7
61
2 to 96
10%
25%
Groysman,Galina
40*
54.1
55
20 to 96
0%
10%
Guinan,Justin T
9
53.6
52
0.1 to 89
5%
15%
Hale,Lyman L
14
38
41.5
1 to 79
35%
10%
Haygood,Shauna M
37*
41
47
0 to 92
25%
20%
Hernandez,Melvin O
46*
56.2
58
19 to 85
0%
25%
Herzog,T ami
51
56.8
60
17 to 93
0%
30%
Hess,Heather E
15*
32
17
0.1 to 78
40%
20%
Hetey,Sara E
44
79
81.5
44 - 90
0%
0%
Hoang,Ha K
18
47.4
51
1 to 82
20%
10%
Hopkins,Anthony B
20
57.3
64
0 to 91*
4%
20%
Horsford,Alisa C
5
38.5
43
1 to 78
25%
25%
Huynh,Janne
34
37.6
29
1 to 95
30%
30%
Kirui, Philemon
5
33.65
43
8 to 78
20%
25%
Kotiah,Sandy D
47*
41.2
54
1.5 to 88
27%
5%
Lewis,Lisa M
15 - 22
40.4
41.5
1 to 82
30%
20%
Lollo,Stephanie
52
53.8
62.5
1 to 85
20%
20%
Louis,Dunchy
1855 to 1999 58.7
63
4 to 78
5%
10%
Majovski,Robert C
14
54.1
59.5
8 to 75
5%
15%
Maragliano,Angela R
9
46.6
50
3 to 82
10%
20%
Martin,Nicole M
46
68
72
19 to 97
0%
10%
Mathews,Marissa L
15
30.6
20
0.5 to 78
40%
25%
Mattiacio,Brian L
4
44.3
47
1 to 85
30%
20%
Milow,Clifford A
M ultiple
Montalbano,Joanne M
5
56.5
55.5
20 to 91
0%
30%
Newell,Shanna M
Unk*
37.4
37.5
0 to 88
25%
25%
Papsidero,Sara A
Unk
53
57.5
10 to 90
15%
15%
Pearlman,Ryan D
54
58.6
61
8 to 88
5%
10%
Penschow,Jonelle L
44*
70
73
41 to 88
0%
0%
Quazi,Shaila
48
46.4
49
8 to 81
10%
25%
Rienbeck,Melissa A
3
57.8
65
1 to 87
10%
10%
Saez, Zugely
Not Done
Sabado,T homas N
Unk
55
68
0 to 91
11%
16%
Sajeski,Jaime L
34
44.9
42
0.4 to 87
15%
35%
Schultz Jr.,William R
3*
69
67
30 to 89
0%
5%
Sherman,Julie J
37
33
35
1 to 78
30%
40%
Siket,Matthew S
Unk*
60.1
66
2 to 90
10%
0%
Sousou,T arek J
46
45.3
52
1 dy to 82 yr
25%
10%
Suk,Elena
C*
41.4
39.5
0.2 to 88
15%
30%
T an,Piek L
48*
35.6
40.5
0 to 76
30%
20%
T aszymowicz,Jodi
48
45.7
48
1 to 82
20%
25%
T illou,Brett T
J*
59.3
65
7 to 95
4%
16%
Vespo, Jacqeuline
62*
52.6
66
10 to 74
5%
10%
Wagner,Eilis B
42
46.65
44
1 to 96
10%
35%
Yates,Gail F
Unk
37
23
0 to 85
37%
16%
Zimerman,Erik
Not Done
S tudent
Immunobiology Class Experiment
Oakwood Cemetery: Dec. 1999
63 Students each surveyed a section
in Oakwood with Markers from the
19th Century and a section with
markers after 1940.
Tombstones prior to 1900
(Left Half of Table)
Tombstones after 1940
(Right Half)
Summary of Results
Next Slide Table
Following Slide Graphic
Averages
50.6
54.3
15.2%
48 out of 58 sections have child deaths
55 out of 58 S ections have young adult deaths
16.5%
Young
S ection
Mean Median
S pan Children Adults
Post 1940
0 to 15 16 to 40
Not Done
Not Given
67.4
78
5 to 100
5%
15%
57
68.6
68
43 to 86
0%
0%
60
72.2
72
11 to 98
5%
0%
68
58.3
67
1 to 90
5%
10%
81
Not Given Not Given Not Given
?
?
C*
73.5
73.5
52 to 93
0%
0%
15
63
63
44 to 81
0%
0%
81
68.6
71.5
28 to 95
0%
0%
64E**
56.3
59
1 to 89
5%
20%
46
61.3
64.5
21 to 84
0%
5%
C
76.9
81
39 to 94
0%
5%
T
55
64.5
8 to 91
5%
15%
M ausoleum
61
68.5
2 to 86
15%
0%
E
53.8
63
3 to 91
5%
15%
M ausoleum A 73.9
75.5
33 to 89
0%
5%
Unclear
102*
M ausoleum*
51*
60
58**
54
8
81
H11
38
64
75
64
81
38
71
Not Done
100
68*
2
P
102
60.1
61.3
68.1
56.6
82.3
81.9
69.5
69
67.1
71.7
66
69.6
60.3
75.1
60.6
66.8
65.1
63
61
76
Not given
82
81.5
71.5
67
73
78.5
71
77
56
80.5
62.5
72
63.5
35 to 82
25 to 87
2 to 95
1 to 84
58 to 98
27 to 96
17 to 99
44 to 91
15* to 95
31 to 94
7 to 103
17 to 102
26 to 104
42 to 102
15 to 89
7 to 72
41 to 89
0%
0%
10%
5%
0%
0%
0%
0%
5%
0%
5%
0%
0%
0%
5%
5%
0%
10%
5%
5%
20%
0%
5%
15%
0%
0%
5%
5%
5%
15%
0%
15%
5%
0%
68.7
59.4
63
50.8
65.8
72.5
66.5
68
Not Done
68
11 to 98
3 to 99
0 to 90
17 to 91
9 to 98
5%
15%
9%
0%
5%
5%
5%
4%
20%
10%
64
76**
I
81
81
58
62
78.8
70.4
75
61.6
73.1
59.4
68.8
78
76
77
61.5
78
60
73
54 to 91
40 to 100
52 to 98
23 to 89
23 to 90
30 to 81
33 to 94
0%
0%
0%
0%
0%
0%
0%
0%
5%
0%
15%
5%
10%
10%
Unk
47
G-2
81
Unk*
76
S
15**
P
J**
81
81
Unk*
Not Done
61
74.8
73
70.6
74.1
72.8
69.9
59.9
76
76
68.5
74.9
59.5
69
77.5
73
76
76
73.5
66.5
71
Not Done
74
70
76
64.5
0 to 85
18 to 95
43 to 96
48 to 95
43 to 97
23 to 107
44 to 91
14 to 90
50 to 95
56 to 99
28 to 89
53 to 90
35a to 88
11%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
10%
0%
0%
0%
5%
0%
20%
0%
0%
5%
0%
20%
67.3
70.8
2.2%
18 out of 58 sections have child deaths
35 out of 58 sections have young adult deaths
6.2%
*4 out of 20 blank
*4 blanks;**1 blank
*4 out 24 blank
*3 out 21 blank
*3 no birth date
*14 unreadable !
*Dates not given
*Ages 2 & 12;1917/18
*3 Y. Adults before 1920
*3 Bidwell Children
*4 blanks,** Y.Ad 1921
Age 17;5/6/1864 Wilderness
*M otor Vehicle Accident
*2 Unread;4 No BD;25 count
Old:8/20 survived past 40 yrs
*2 Unreadable markers
M other & 2 Children 1988
Multiple
*6 Unread;**2 Unread;Harley
*Anomalous ;1873-84 All
*2 Unread; 19 done each
*3 post 1955 deaths
*21 Counted;1 1947 Exclud
*6 unreadable
*10 Read;**1932 early death
*25 Read;1 Unread;**26 Read
* 4 Blanks;All 1926-44!
*Used 15; Xcld 5 prior 1930
a = WWII KIA
Summary of Class Experiment: BIO 447 Immunobiology
Oakwood Cemetery Deaths by Age: 19th Century vs Post 1940
Prior to 1900
Median
Mean
50.6
54.3
0 to 15 yrs
15.2%
16 to 40 yrs
16.5%
After 1940
Median
Mean
67.3
70.8
0 to 15 yrs
2.2%
16 to 40 yrs
6.2%
48 out of 58 sections have child deaths
18 out of 58 sections have child deaths
55 out of 58 Sections have young adult deaths
35 out of 58 sections have young adult deaths
Approximately 180 deaths prior to age 15
Approximately 25 deaths prior to age 15
“Now we know and treat and seldom do we
suffer death to stalk the nursery”
(Song of the Oakwood Children)
Median Survival: 50.6 yrs
180 Children
25 Children
Median Survival: 67.3 yrs
A 19th Century American Family History
Eddie: 1846-1850
Willie: 1850-1962
Thomas (“Tad”)
1853 - 1871
Robert: 1843-1926
(Had a son: 1873 – 1890;
Two daughters: 1869-1938;
1875-1948)
Note on a Syrian Playground, November, 2012
Rachel, they make war on children.
Now we die by our brothers’ hand!
(Song of the Oakwood Children)
What Have Vaccines Done For Us?
(See Figure 18-1 Kuby, 3rd Edition)
Antiviral Vaccines, From Roitt, 4th Edition, Figure 19.3
Data for U.S.
VacSave1
What Have Vaccines Done For Us?
(See Figure 18-1 Kuby, 3rd Edition)
Antiviral Vaccines, From Roitt, 4th Edition, Figure 19.3
Data for U.S.
VacSave2
What Have Vaccines Done For Us?
Greatest Single Cause of Death for
Humankind Since the Beginning of
Civilization:
Smallpox
Deaths from Smallpox
1977 - 2004:
0
Measles Vaccine (Introduced 1962)
Reappearance in 1980’s in
unvaccinated or singly
vaccinated young people
Passive and Active Immune Protection
Passive: Transfer of Pre-existing Immune Response
Naturally from Mother to Child
Trans-placental
Breast Feeding
Artificially in Medical Treatment
Adoptive - Donor to Recipient
Usually Antibodies; Could be Lymphocytes
Anti-toxin Antibodies:
Treatments for toxins already present:
Rabies, Diphtheria, Tetanus, Botulinus Poisoning
Provides Limited Duration Prophylaxis
Active: Induce Immune Response Directly in Protected
Individual
Active Immunization
Prophylactic Immunity based on Immunological Memory
Controlled Artificial Infection
• Active Disease-causing organism: Smallpox Pustule
•
•
•
•
•
•
•
•
•
•
•
Exudates - Variolation
Cross-reactive related live organism: Vaccinia (cowpox virus) Vaccination
Attenuated Live Organisms
Inactivated Killed Organisms
Inactivated Exotoxins - Diphtheria, Tetanus
Purified Macromolecular Antigens
Bacterial Capsular Polysaccharides
Membrane Antigens: Plasma Membrane or Virus Envelope
Cloned Antigenic Gene Products
Synthetic Antigens
Anti-idiotypic Antibodies (antigen mimics)
DNA vaccines
Live Attenuated Vaccines
Against Viral Diseases
• Polio (Sabin Vaccine) - Also Use Killed Vaccine
(Salk)
• Measles (“Rubeola”)
• Mumps
• Rubella (“3-Day Measles” or “German Measles”
• Yellow Fever
• Hepatitis A (Live and killed versions)
Against Bacterial Disease
• Tuberculosis
Killed Whole Organism Vaccines
Against Viral Diseases
• Polio (Salk Vaccine) - Also Use Attenuated Live
Vaccine (Sabin)
• Rabies
• Influenza (strain-specific only)
• Hepatitis A (Live and killed versions)
Against Bacterial Disease
•
•
•
•
•
Pertussis (Whooping Cough)
Typhoid
Cholera (combined with toxin subunit vaccine)
Plague (short-term protection only)
Pneumococcal Pneumonia
Anti-Toxin Vaccines
Clostridium tetani
Formalin-inactivated
exotoxin
Corynebacterium
diphtheriae
Formalin-inactivated
exotoxin
Vibrio cholerae
Exotoxin subunit (beta
subunit)
Anti-Diphtheria Toxin Vaccine
(Figure 19-5 Roitt, 4th Edition)
Purified Macromolecular Antigen Vaccines
Capsular Polysaccharides –
Must Be Conjugated to Protein Carriers
to Get Memory Responses
• Hemophilus influenza B (Bacterial meningitis)
• Neisseria meningitidis
• Streptococcus pneumoniae
Recombinant Cell-Surface Antigen
• Hepatitis B
Vaccines Generally Given to All
Tetanus (Toxoid)
Diphtheria (Toxoid)
Pertussis (Killed virus)
• Given Together as DPT; Periodic Boosters for Tetanus &
Diphtheria Required
• Polio (Killed or Attnenuated Live Virus)
Measles (Attenuated live virus)
Mumps
(Attenuated live virus)
Rubella
(Attenuated live virus)
Chicken Pox (Attenuated live Varicella Zoster)
Hemophilus Influenzae (Polysaccharide capsular
component); For bacterial meningitis (not
related to flu vaccine)
Vaccines for Groups at Special Risk
Tuberculosis (BCG) Depending on Locale and Travel
Hepatitis B (Recombinant Surface Ag)
• Medical personnel; drug addicts; contacts
Rabies - Animal workers or post exposure
Influenza (Killed virus strains) - At risk and Elderly
Pneumococcal pneumonia (Killed bacteria) - Elderly
Meningitis (Capsular Polysaccharide) Yellow fever (Killed pathogen)
Typhoid (Killed pathogen)
Cholera (Mutant pathogen; Toxoid Subunit)
Hepatitis A (Killed or attenuated virus)
Varicella-zoster (Attenuated virus) -
What Vaccines Don't We Have?
Viral Diseases
• HIV - Presence of variants and Immunosuppression
Ignorance of immunogenic antigens to use
• Herpes Viruses (Papilloma virus vaccine announced
Fall, 2002)
• Adenoviruses, Rhinoviruses - Multiple types
Bacterial Diseases
•
•
•
•
•
Staphylococci
Group A Streptococci
Mycobacterium leprae (Some benefit from BCG)
Treponema pallidum (syphilis)
Non-Hemophilus and Non-Neisseria Bacterial Menigitis
Fungal Pathogens
• Candida
• Pneumocystis
More Vaccines That We Don't Have
Protozoa
• Malaria
• Trypanosomiasis
Sleeping Sickness
Chagas Disease - Autoimmunity and Immunosupression
• Leishmaniasis
Multicellular Parasites - Worms
• Schistosomiasis
Prophylactic and Therapeutic Cancer Vaccines
How Can We Get What We Don't Have?
Combination Epitope Vaccines
(Multivalent Subunit Vaccines )
Delivery Vehicles and Adjuvants
Anti-Idiotype Vaccines
Naked DNA Vaccines
Engineered Vector and
Antigen-presenting Cell Vaccines
Mucosal-Active (IgA Isotype) Vaccines
Non-Scientific Problems with Vaccines
Medical Risks to Individuals vs "Herd Immunity"
Immediate Risks to the Individual
Long-term Benefits the the Group and the Individual
Very low percentage risks multiplied over huge populations
Side-Reactions, Limited Efficacy, Limited Duration
Costs and Ability to Pay
Geographical Distribution
"Orphan" and "Third World" Diseases
Limitations in Vaccine Production for Diseases with
High Rate of Strain Variation
Autonomy, Parental rights, Religious Freedom
Public Acceptance and Ignorance of History
Measles Vaccine (Introduced 1962)
Reappearance in 1980’s in
unvaccinated or singly
vaccinated young people
Risks from Whooping Cough Disease
(Pertussis) vs. Risks from Pertussis Vaccine
Pertussis Vaccine
Seizures: 1 in 1,750
Encephalytis: 1 in 110,000
Brain Damage: 1 in 310,000
Death: 1 in 1,000,000
Whooping Cough Disease
Seizures: 1 in 25 to 1 in 50
Encephalytis: 1 in 1,000 to 1 in 4,000
Brain Damage: 1 in 2,000 to 1 in 8,000
Death: 1 in 200 to 1 in 1,000
Difference in Death Rate:
Natural Exposure to Whooping Cough
vs Exposure to Pertussis Vaccine:
1,000-fold to 5,000-fold increased Risk
View Animation on Textbook Web-site: (Linked to Course
Home Page) - Vaccines
Also Molecular Visualizations: Influenza Hemmagglutinin
Survey of Oakwood Cemetery done by BIO 447 Class, 1999:
Section with Burials Prior to 1900 vs
Sections with Burials after 1940
Song of the Oakwood Children:
Rachel Amelia Cody, June 1840
(Your response is anonymous. No name will be recorded)
With respect the use of Turning Point NXT Transmitter
system in BIO 447 and its contribution to the standards of
the course:
The next slide will ask what you think of how well the
system works
0 of 94
or
cc
ep
ta
b
0%
Po
0%
le
d
0%
A
O
ut
sta
n
di
ng
0%
Response Grid
0%
Te
rr
ib
le
Outstanding
Good
Acceptable
Poor
Terrible
G
oo
1.
2.
3.
4.
5.
(Your response is anonymous. No name will be recorded)
With respect to how well the Turning Point NXT
Transmitter system works in the classroom:
1.
2.
3.
4.
5.
It works outstandingly well
It works well
It is OK
It is pretty unreliable and
hard to make work
It doesn’t work well at all
It
wo
rk
s
ou
ts
ta
n
di
ng
ly
we
It
ll
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0% 0% 0% 0% 0%
0 of 94
Anti-Idiotypic
Antibodies
(Figure 19.9, Roitt, 4th Edition)
IdioVacc