Immunotherapy and Vaccination

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Immunotherapy and Vaccination Chapter 14 Also
see on-line Influenza resource at
http//www.influenzareport.com/ir/vaccines.htm
The Parents' Guide to Childhood Immunizations
http//www.cdc.gov/nip/publications/Parents-Guide
/2005-parents-guide.pdf
Immunotherapy Using Immune system to fight
disease Vaccination is most familiar
Self-Test Questions Intro both A 1 5, 7,
8 B 1 - 8 C - G all
Disease Virus Small pox variola Cow
pox vaccinia Chicken pox varicella
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Edward Jenner and the origin of Immunotherapy
(vaccination) Small pox caused by variola
virus Induced immunity dates to ancient
Chinese -- practiced Variolation -- brought
to England in 1700s -- lead to the Royal
experiment Jenner discovered protective effect
of cow pox -- vaccinia virus -- vacca
Latin for cow -? vaccination WHO irradicated
small pox in 1970s
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What are different types of immunization? Passive
Immunization -- direct transfer of protective
antibodies -- no immunological memory Active
Immunization -- activation of immune
response -- immunological memory Therapeutic
Immunization -- treat existing disease
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Passive Immunization to treat Fetal
Erythroblastosis Conditions mother Rh father,
1st and 2nd fetuses are Rh Rh Immune
hemolysis Rhogam
Given 24-48 hours after 1st pregnancy
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Active Vaccination What are some important
considerations in the design of
vaccines? Characteristics of pathogen disease
Intra- vs extra-cellular short or long
incubation acute or chronic disease Antigenic
stability route of infection Characteristics of
vaccine appropriate response booster safety stabil
ity, cost
Characteristics of patient Infants (vs adults)
have lower -- GC activity -- Plasma cell
production -- TH1 response Maternal Ab
black responses
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What are the recommended childhood
vaccines? Combined vaccines Why are boosters
needed? Other vaccines for special
needs TB, anthrax, plague, yellow fever,
etc

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effectiveness Calculated under field
conditions i.e., real world conditions --
religious/cultural opposition -- available
medical facilities -- etc
Vaccine efficacy vs Efficacy under
trial conditions incidence among those
administered 1- ------------------------------
------------- ------------------------------------
------- incidence among those not
administered
Example efficacies Diphtheria 87-96
Tetanus gt90 Oral polio 90-100
Mumps/Measles/Rubella 90-95 HIV
vaccine trials 150 vaccines developed 6 have
made it to efficacy testing 2009 1st with
efficacy (31) 2007 had negative
efficacy Malaria vaccine trial 2011 45 56
Is 100 efficacy necessary? -- herd
immunity Cases per Year Decrease
before in in Cases (average) 2003 per Year
Diphtheria 175,885 1 99.9 Hib (lt5 yrs old)
20,000 (est.) 259 98.8 Measles 503,282 56
99.9 Mumps 152,209 231 99.9 Pertussis
147,271 11,647 92.1 Polio
(paralytic) 16,316 0 100.0 Rubella 47,745
7 99.9 Smallpox 48,164 0 100.0 Tetanus
1,314 20 98.5
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How are vaccines made? Dead (inactivated)
pathogens IPV Inactivated polio vaccine
Salk vaccine old pertussis of DPT --
Bordetella pertussis Live attenuated
pathogens MMR measles, mumps, rubella
viruses OVP -- oral polio vaccine Sabin
vaccine Subunit / Peptide components HBsAG --
Hepititis B surface antigen Flu purified HA
NA antigens Conjugates (polysaccharides coupled
to protein carrier) HiB Haemophilus influenzae
type B PCV pneumococcal conjugate
vaccine Toxoids DTaP -- diphtheria, tetanus
toxoids acellular pertussis molecular
component
Cell cultured virus
Remember Adjuvants? -- increase immune response
e.g., aluminum hydroxide
McGraw-Hill Vaccines
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What are pros and cons of different types of
vaccines? Dead (inactivated) pathogens pros ma
y be safer more stable than attenuated cons w
eaker cell mediated response boosters contaminan
ts pertussis endotoxin in old DPT Live
attenuated pathogens pros better cell-mediated
response cons reversion -- Sabin polio (Types
1 2) infection in immunodeficient
patients less stable Molecular components
pros No living pathogen present very
stable cons fewer epitopes weaker cell
mediated response
Vaccine type Example reactions
Vaccines from Chicken eggs and cell cultures Allergic reactions Contaminating pathogens
Vaccines with Preservatives Allergic reactions
Live attenuated Susceptibility during preganncy and among immunodepressed
Dead whole cell Contamination with toxins
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Why do we not have vaccines for serious protozoal
diseases -- malaria, African sleeping
sickness Plasmodium causes Malaria -- Anopholes
mosquito is vector Trypanosoma cause ASS --
tsetse fly is vector Complex life
cycles Chronic diseases Undergo Antigenic
Shift Trypanosoma carries 1000 VSG
genes (variant surface glycoprotein) 1 of
parasites shift AG
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Influenza the disease Principal virus subtypes
-- A B Key surface antigens Hemaglutinin --
HA Neuraminidase NA -- numbered 1,2,3,
etc Causes of seasonality unclear ?
antigenicity/ infectiousness social
interactions environmental conditions Current
circulating forms H3N2, H1N1, H1N2, 36K
deaths 200,000 hospitalizations
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Influenza cont Circulating stains vary
annually -- antigenic drift -- vaccine must
accommodate Recent vaccines contain A -- New
Caledonia/20/99 (H1N1) A -- Wisconsin/67/2005
(H3N2) B -- Malaysia/2506/2004 Vaccines
types Injection inactivated whole virus
or purified HA NA antigens Nasal spray
FluMist -- cold adapted attenuated Prepared
in eggs Capacity only 300 x 106 doses
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Pandemic Flu Antigenic-Shift can
occur History 1918 Spanish Flu (H1N1 40 mil
dead) 1957 Asian Flu (H2N2 1 mil dead 1968
Hong Kong Flu (0.75 mil dead) -- AG-shift from
H2N2 to H3N2 Swine Flu 2009 H1N1 vaccine
(influenza A/California/07/2009) 15 µg HA
or 106.5-107.5 pfu of live attenuated
virus Challenges to vaccination Development
time Production capacity (use of
eggs?) Distribution Economics Vaccination
strategy
Current spread of H5H1
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Modern Immunotherapies Immunotherapies for
Autoimmune disorders / transplant rejection 1)
B-cell elimination -- e.g., Rituximab -- mAb
against CD-20 (Ca channel?) -- triggers
B-cell destruction At advent of Cancer
Immunotherapy -- Long history Coleys
Toxins -- immune activation What are Cancer
Antigens?
Rituximab mechanisms
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Other Types of Cancer Immunotherapies 2)
Checkpoint inhibitors -- Why do many cancers
evade immune destruction? 3) Cancer
vaccines - target cancer-specific antigens 4)
Cell coupling -- Bispecific molecules (mAb)
-- e.g., Blinatumomab (Blincyto)
? B-cell leukemia -- mAb Fabs against
CD3 CD19
Checkpoint inhibitors
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Types of Cancer Immunotherapy, cont 5) Cell
Therapy May involve Infusion of A.
Hematopoietic stem cells from either umbilical
cord blood, peripheral blood, or bone marrow
cells -- commonly used for leukemia, etc B.
Dendritic cells C. T cells or NK cells treated
in vitro to recognize and kill cancer cells
directly. -- engineer to produce Anti- tAG TCR