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Vaccines in
Immunobiologyand
Medicine
Folder title: Vaccines
Updated: December 06, 2011 VaccTtle
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?
InHealth
Immunology in Human and Animal Health and Disease
What can we make it do
for us?ImmUse
KEY FEATURES OF SPECIFIC ADAPTIVE IMMUNITY IN HISTORY
Freedom from Plague after Surviving First Exposure
Immunity Exists
Susceptibility to Other DiseasesEven After Surviving Plague
Immunity isSpecific
Deliberately Induce Small-pox toProtect Against Later Exposure
Immunity hasMemory
Induce Non-pathogenic Cow-pox to Protect Against Virulent Small-pox (Vaccination)
Related Antigensare Cross-Reactive
Resistance to Chicken Cholera
after Surviving Exposure to Weakened Chicken Cholera Bacilli (Attenuated Vaccines)
Antigens can be separated frompathogenicity
ImHistry
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?
VacQuest
Oakwood Cemetery Burials Section 29 Survey by Tom Fondy 10-Nov-96Filename: OakSec29.doc Age inName Born Died Years RemarksRobbie Bonta 1868 1875 7 March 22, 1875, Age 6 yrs & 8 mos.; Son of SamuelKatherine T. Bonta 1864 1945 81Frank M. Bonta 1845 1939 94Helen A. Plumb 1853 1886 33 Jan. 20, 1886; Wife of Frank M. BontaLaura J. Benner 1850 1876 25 Died Feb. 9, 1876; Wife of Frank M. BontaSamuel 1873 1874 1.5 Son of F & L Bonta; Aged 1 yr & 7 mosGeorge L. Bonta 1848 1922 74H. Benner 1876 1888 12 Born Feb. 9, 1876 (See Laura S. Benner)Blank Unk Unk Unk Next to H. Benner; Tombstone is BlankFrankie L. Curtis 1864 1875 11 Born Sept. 22, 1864; Died Feb. 14, 1875Frances B. Curtis 1844 1932 88Nathan L. Curtis 1836 1922 86Roger L. Jones 1872 1951 79Mary C. Jones 1875 19??Fannie Lathrop 1871 1879 8 Died Dec. 27, 1879; Age 8 yrs, 8 mos, 3 dysRachel Amelia Cody 1840 1840 0.1 d. August 8, 1840; Age 6 wks and 4 dys;
Daughter of Narcissa & Niel? Cody Unk Unk Faded (Could be Narcissa or Niel Cody)
Missing Unk Unk UnkUnknown 1800 1883 83George Chapman Lathrop 1811 1898 87Unknown Unk Unk Unk Tombstone ToppledGeorge Nelson 1847 1849 2 Son of Benjamin & Permela LathropGeorge Chapman 4 Aged 3 yrs, 10 mos, 16 dys Average Age: 43.1Notes: 10 died aged 6 wks to 33 yrs. 50% of Identifiable Dates! 8 died aged 74 to 94.
See Verses by TPFondy at http://tpfondy.mysite.syr.edu/Song of the Oakwood ChildrenVerses and Self-running Presentation
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.xlsOakwood Cemetery DataUpdated: December 5, 1999
Young YoungStudent Section Mean Median Span Children Adults Section Mean Median Span Children Adults
Prior 1900 0 to 15 16 to 40 Post 1940 0 to 15 16 to 40
Abrams, Marshall 46 Not given Not Given 0 to 103 17% 13% Not Done
Arace,Jennifer A Not Given 46.7 47.5 1 to 89 25% 15% Not Given 67.4 78 5 to 100 5% 15%
Arcuri, Phil 14 63.15 64.5 25 to 87 0% 20% 57 68.6 68 43 to 86 0% 0%
Azeez,Mohamed C 50* 59.3 78.5 4 to 109 19% 6% 60 72.2 72 11 to 98 5% 0% *4 out of 20 blank
Berard, Eric 29 45.1 48 2 to 74 10% 25% 68 58.3 67 1 to 90 5% 10%
Boyer, James 20A Not given Not Given Not Given ? ? 81 Not Given Not Given Not Given ? ?
Broderick,Lori 48 48.1 59.5 1 to 89 25% 10% C* 73.5 73.5 52 to 93 0% 0%
Brusgul,Anthony M 10 56.4 71 1 to 94 15% 20% 15 63 63 44 to 81 0% 0%
Burpee,Stacey D 9 67.5 75.5 1 to 94 5% 5% 81 68.6 71.5 28 to 95 0% 0%
Clark,Sharon K 48W* 60.2 56 20 to 102 0% 5% 64E** 56.3 59 1 to 89 5% 20% *4 blanks;**1 blank
Covington,Ari-Anna M 46* 55.6 71 1 to 96 20% 5% 46 61.3 64.5 21 to 84 0% 5% *4 out 24 blank
Darling,Jennifer S 35* 47.2 57 1 to 97 28% 17% C 76.9 81 39 to 94 0% 5% *3 out 21 blank
Di Re,Vicky 47 41 51.5 0 to 85 40% 5% T 55 64.5 8 to 91 5% 15%
Domville,Shelley L 7 51.9 52.5 0 to 84 10% 10% Mausoleum 61 68.5 2 to 86 15% 0%
Douangnouanexay,Ladda 58* 59.9 69.5 6 to 94 5% 11% E 53.8 63 3 to 91 5% 15% *3 no birth date
Fernandez,Jason E 15 60.5 66 9 to 83 5% 10% Mausoleum A 73.9 75.5 33 to 89 0% 5%
Fogu,Brian S See Julie Sherman
Gengo,Jessica 46* 55.7 61 2 to 96 10% 25% Unclear 60.1 63 35 to 82 0% 10% *14 unreadable !
Groysman,Galina 40* 54.1 55 20 to 96 0% 10% 102* 61.3 61 25 to 87 0% 5% *Dates not given
Guinan,Justin T 9 53.6 52 0.1 to 89 5% 15% Mausoleum* 68.1 76 2 to 95 10% 5% *Ages 2 & 12;1917/18
Hale,Lyman L 14 38 41.5 1 to 79 35% 10% 51* 56.6 Not given 1 to 84 5% 20% *3 Y. Adults before 1920
Haygood,Shauna M 37* 41 47 0 to 92 25% 20% 60 82.3 82 58 to 98 0% 0% *3 Bidwell Children
Hernandez,Melvin O 46* 56.2 58 19 to 85 0% 25% 58** 81.9 81.5 27 to 96 0% 5% *4 blanks,** Y.Ad 1921
Herzog,Tami 51 56.8 60 17 to 93 0% 30% 54 69.5 71.5 17 to 99 0% 15%
Hess,Heather E 15* 32 17 0.1 to 78 40% 20% 8 69 67 44 to 91 0% 0% Age 17;5/6/1864 Wilderness
Hetey,Sara E 44 79 81.5 44 - 90 0% 0% 81 67.1 73 15* to 95 5% 0% *Motor Vehicle Accident
Hoang,Ha K 18 47.4 51 1 to 82 20% 10% H11 71.7 78.5 31 to 94 0% 5%
Hopkins,Anthony B 20 57.3 64 0 to 91* 4% 20% 38 66 71 7 to 103 5% 5% *2 Unread;4 No BD;25 count
Horsford,Alisa C 5 38.5 43 1 to 78 25% 25% 64 69.6 77 17 to 102 0% 5%
Huynh,Janne 34 37.6 29 1 to 95 30% 30% 75 60.3 56 26 to 104 0% 15% Old:8/20 survived past 40 yrs
Kirui, Philemon 5 33.65 43 8 to 78 20% 25% 64 75.1 80.5 42 to 102 0% 0%
Kotiah,Sandy D 47* 41.2 54 1.5 to 88 27% 5% 81 60.6 62.5 15 to 89 5% 15% *2 Unreadable markers
Lewis,Lisa M 15 - 22 40.4 41.5 1 to 82 30% 20% 38 66.8 72 7 to 72 5% 5%
Lollo,Stephanie 52 53.8 62.5 1 to 85 20% 20% 71 65.1 63.5 41 to 89 0% 0%
Louis,Dunchy 1855 to 1999 58.7 63 4 to 78 5% 10% Not Done
Majovski,Robert C 14 54.1 59.5 8 to 75 5% 15% 100 68.7 72.5 11 to 98 5% 5%
Maragliano,Angela R 9 46.6 50 3 to 82 10% 20% 68* 59.4 66.5 3 to 99 15% 5% Mother & 2 Children 1988
Martin,Nicole M 46 68 72 19 to 97 0% 10% 2 63 68 0 to 90 9% 4%
Mathews,Marissa L 15 30.6 20 0.5 to 78 40% 25% P 50.8 Not Done 17 to 91 0% 20%
Mattiacio,Brian L 4 44.3 47 1 to 85 30% 20% 102 65.8 68 9 to 98 5% 10%
Milow,Clifford A Multiple MultipleMontalbano,Joanne M 5 56.5 55.5 20 to 91 0% 30% 64 78.8 78 54 to 91 0% 0%
Newell,Shanna M Unk* 37.4 37.5 0 to 88 25% 25% 76** 70.4 76 40 to 100 0% 5% *6 Unread;**2 Unread;Harley
Papsidero,Sara A Unk 53 57.5 10 to 90 15% 15% I 75 77 52 to 98 0% 0%
Pearlman,Ryan D 54 58.6 61 8 to 88 5% 10% 81 61.6 61.5 23 to 89 0% 15%
Penschow,Jonelle L 44* 70 73 41 to 88 0% 0% 81 73.1 78 23 to 90 0% 5% *Anomalous ;1873-84 All
Quazi,Shaila 48 46.4 49 8 to 81 10% 25% 58 59.4 60 30 to 81 0% 10%
Rienbeck,Melissa A 3 57.8 65 1 to 87 10% 10% 62 68.8 73 33 to 94 0% 10%
Saez, Zugely Not Done
Sabado,Thomas N Unk 55 68 0 to 91 11% 16% Unk 61 69 0 to 85 11% 0% *2 Unread; 19 done each
Sajeski,Jaime L 34 44.9 42 0.4 to 87 15% 35% 47 74.8 77.5 18 to 95 0% 10%
Schultz Jr.,William R 3* 69 67 30 to 89 0% 5% G-2 73 73 43 to 96 0% 0% *3 post 1955 deaths
Sherman,Julie J 37 33 35 1 to 78 30% 40% 81 70.6 76 48 to 95 0% 0%
Siket,Matthew S Unk* 60.1 66 2 to 90 10% 0% Unk* 74.1 76 43 to 97 0% 0% *21 Counted;1 1947 Exclud
Sousou,Tarek J 46 45.3 52 1 dy to 82 yr 25% 10% 76 72.8 73.5 23 to 107 0% 5%
Suk,Elena C* 41.4 39.5 0.2 to 88 15% 30% S 69.9 66.5 44 to 91 0% 0% *6 unreadable
Tan,Piek L 48* 35.6 40.5 0 to 76 30% 20% 15** 59.9 71 14 to 90 0% 20% *10 Read;**1932 early death
Taszymowicz,Jodi 48 45.7 48 1 to 82 20% 25% P 76 Not Done 50 to 95 0% 0%
Tillou,Brett T J* 59.3 65 7 to 95 4% 16% J** 76 74 56 to 99 0% 0% *25 Read;1 Unread;**26 Read
Vespo, Jacqeuline 62* 52.6 66 10 to 74 5% 10% 81 68.5 70 28 to 89 0% 5% * 4 Blanks;All 1926-44!
Wagner,Eilis B 42 46.65 44 1 to 96 10% 35% 81 74.9 76 53 to 90 0% 0%
Yates,Gail F Unk 37 23 0 to 85 37% 16% Unk* 59.5 64.5 35a to 88 0% 20% *Used 15; Xcld 5 prior 1930
Zimerman,Erik Not Done Not Done a = WWII KIA
Averages 50.6 54.3 15.2% 16.5% 67.3 70.8 2.2% 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
Immunobiology Class ExperimentOakwood Cemetery
Tombstones prior to 1900(Left Half of Table)
Tombstones after 1940(Right Half)
Summary of Results
Next Slide
Prior to 1900 After 1940Median Mean 0 to 15 yrs 16 to 40 yrs Median Mean 0 to 15 yrs 16 to 40 yrs50.6 54.3 15.2% 16.5% 67.3 70.8 2.2% 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
Summary of Class Experiment: BIO 447 ImmunobiologyOakwood Cemetery Deaths by Age: 19th Century vs Post 1940
What Have Vaccines Done For Us?(See Figure 18-1 Kuby, 3rd Edition)
Antiviral Vaccines, From Roitt, 4th Edition, Figure 19.3Data for U.S.
VacSave1
What Have Vaccines Done For Us?(See Figure 18-1 Kuby, 3rd Edition)
Antiviral Vaccines, From Roitt, 4th Edition, Figure 19.3Data 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
Smallpox
Passive and Active Immune ProtectionPassive: 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
Pass&Act
Active ImmunizationProphylactic 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
ActImmun
Vaccines based on active immunization have one big advantage over vaccines based on
passive transfer of immunity.
What is that big advantage?
0 of 5
Vaccines based on passive transfer of immunity have one big advantage over vaccines based on active immunization.
What is that big advantage?
0 of 5
Live Attenuated VaccinesAgainst Viral Diseases• Polio (Sabin Vaccine) - Also Use Killed Vaccine
(Salk)• Measles• Mumps• Rubella• Yellow Fever• Hepatitis A (Live and killed versions)
Against Bacterial Disease• Tuberculosis
LiveVacc
Killed Whole Organism VaccinesAgainst 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
KillVacc
Anti-Toxin Vaccines
Clostridium tetani
Corynebacterium diphtheriae
Vibrio cholerae
Formalin-inactivated exotoxin
Formalin-inactivated exotoxin
Exotoxin subunit (beta subunit)
AntiTox
Anti-Diphtheria Toxin Vaccine(Figure 19-5 Roitt, 4th Edition)
DiphSave
Diphtheria, tetanus, and cholera vaccines are directed toward a _ _ _ _ _ produced by the infectious organism
0 of 94
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
PureAg
Vaccines Generally Given to AllTetanus (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)
GenVacc
Vaccines for Groups at Special RiskTuberculosis (BCG) Depending on Locale and TravelHepatitis B (Recombinant Surface Ag)• Medical personnel; drug addicts; contactsRabies - Animal workers or post exposureInfluenza (Killed virus strains) - At risk and ElderlyPneumococcal 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) -
SpecVacc
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
VacNeed1
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
VacNeed2
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
VaccsGet
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
Problems
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, to 4,000
Brain Damage: 1 in 2, to 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
Whooping
View Animation on Textbook Web-site: (Linked to Course Home Page) - Vaccines
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 XR 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
Outst
andin
g
Goo
d
Acc
epta
ble P
oor
Ter
rible
0% 0% 0%0%0%
1. Outstanding2. Good3. Acceptable4. Poor5. Terrible
Response GridResponse Grid
0 of 94
(Your response is anonymous. No name will be recorded)With respect to how well the Turning Point XR Transmitter system works in the classroom:
It w
orks o
utstan
dingl
y well
It w
orks w
ell
It is
OK
It is
pre
tty u
nrelia
ble an
d...
It do
esn’t
work w
ell at
all
0% 0% 0%0%0%
1. It works outstandingly well
2. It works well
3. It is OK
4. It is pretty unreliable and hard to make work
5. It doesn’t work well at all
0 of 94
Anti-Idiotypic
Antibodies (Figure 19.9, Roitt, 4th Edition)
IdioVacc