Vaccines in

Immunobiologyand

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 toProtect Against Later Exposure Immunity has Memory

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 beseparated frompathogenic 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 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

19 Identifiable persons with dates.8 are children 0 to 12 years of age!

(Also a child. Should be blue)

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: 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 TableFollowing Slide Graphic

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

“Now we know and treat and seldom do we suffer death to stalk the nursery”(Song of the Oakwood Children)

180 Children

25 Children

Median Survival: 50.6 yrs 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 19.3Data 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

Measles Vaccine (Introduced 1962)

Reappearance in 1980’s in unvaccinated or singly vaccinated young people

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

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

Live Attenuated VaccinesAgainst 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 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

Anti-Toxin Vaccines

Clostridium tetani

Corynebacterium diphtheriae

Vibrio cholerae

Formalin-inactivated exotoxin

Formalin-inactivated exotoxin

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 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)

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) -

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 110,000Brain 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 4,000Brain 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

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 NXT

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