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Basic Vaccinology:
Why Vaccines Work or Don't Work
Dr. Dan Grooms, Michigan State University

.

1
Objectives
Lets think beyond just giving “shots”







What are Vaccines
Types of Vaccines
Vaccine Failure
Vaccine Handling
Vaccine Risks
Process of Developing a Vaccine Protocol

2
What Are Vaccines
 Substances that are designed to stimulate an immune
response that reduces the risk of a detrimental
condition
 Substances = antigens
 Immune Response = complex response to antigens
 Risk Reduction = no vaccines are 100% effective
 Detrimental Condition = disease, pathology, death, etc

3
Vaccines Types
Attenuated
Killed
Bactrin
Autogenous

Virulent
Toxoids
Recombinant
Anti-toxin

4
Attenuated Vaccines





Also called “modified-live” or “live” vaccines
Live replicating organism with reduced virulence
Virus or Bacteria
Have been manipulated to reduce or eliminate their
ability to cause disease
 In order to work, they must replicate!!

5
Attenuated Vaccines
 Advantages
 Closely simulate natural infection
 Stimulate humoral and cell mediated immunity
• Important for intracellular organisms such as viruses
 Adjuvants not as necessary
 Generally cheaper (Valley Vet On-Line 12-09-13)
• Pyramid 5 (MLV) 10 ds = $11.99
• Triangle (killed) 10 ds = $15.65

6
Attenuated Vaccines
 Disadvantages
 Potential to cause pathology
• Replicating organism can cause mild signs - Brucellosis
• Intact virulence - BVDV, IBR
• Potential for reversion to virulence – low, low risk
 Contamination
• Jencine(4-way live vaccine) contaminated with non-cytopathic
BVDV

 Stability

7
Killed vaccine
 Dead organism
 Bactrin = Killed bacterial suspension

 Key is maintaining antigenic integrity
 Usually require adjuvants to adequately
stimulate immune system

8
Adjuvants
 Aid in stimulating immune response to antigen and
stabilizing vaccines
 Do not confer immunity

 Mechanisms
 Depot – prolonged exposure
• Oil adjuvants
 Irritants – amplify response around target antigens
• Aluminum hydroxide
• Toxins

• Adjuvants are not innocuous
9
Killed Vaccines
 Advantages
 Generally safer
• No disease due to virulent organism
• No contamination
 Greater stability

 Disadvantages
 Hypersensitivity reactions (adjuvants, toxins or large antigen

loads)
 Endotoxins
 More costly
• Pyramid 5 (MLV) 10 ds = $11.99
• Triangle (killed) 10 ds = $15.65

10
Toxoid
 Toxins are the major “virulence” factor of some
bacteria which cause disease:
 Toxoids contain chemically altered toxins
 Stimulate neutralizing antibodies to the toxin
 Examples
 Clostridium
• Tetnus toxoid
• C. perfringes C & D toxoid

 Mannheimia haemolytica
• Leukotoxin

 E.coli
• Endotoxic mastitis
11
Autogenous Vaccines
 Made against “farm specific” pathogen
 Specific rules regulate their production
 Can only be used on the farm that organism was derived from

 Generally used when effective commercial vaccine is not
available
 Example

• Mycoplamsa bovis
• Clostridium perfringes
• Staph aureus

12
Vaccine Failure

13
Vaccine Failure
 REMEMEMBER - Vaccines are not 100% effective
 They are a tool to use in conjunction with other disease control tools

 However, there are things that can reduce efficiency
 Incorrect Administration
 Correct Administration

14
Vaccine Failure
 Incorrect Administration
 Label directions not followed

15
Follow the Directions

16
-Dairy DisasterThe case of not reading the
label

17
Dairy Disaster
 150 lactating cow dairy
 Acute out break of pneumonia in lactating herd
 Necropsy
 Severe Acute Emphysematous Bronchopneumonia
• Bovine Respiratory Syncytial virus
• Mannheimia Pasteurella

 45 vows died
 Entire herd treated with Ampicillin
 Lost milk for ~1 week
18
19
Dairy Disaster
 Investigation
 Recent purchase of new clean-up bull
 Herd had been using a modified live viral vaccine that

DID NOT contain BRSV.
 Admitted, they had not read the label and purchased
from catalog because it was less expensive.

 Primary BRSV outbreak with secondary
Mannheimia haemolytica pneumonia = disaster!!

20
Vaccine Failure
 Incorrect Administration
 Label directions not followed

 Correct Administration
 Poor Vaccine handling

21
Vaccine Handling
• Vaccines are biological in nature, therefore very
sensitive to the environment.
• Damaging the vaccine components reduces the chance
of stimulating effective immune response
• Improper vaccine handling = Vaccine Failure

22
Vaccine Handling
• Store refrigerated
– 40o F (4 Co)
– Not a bad idea to have internal
thermometer to monitor fridge
temp!

• DO NOT FREEZE
• Transport in cooler
• Stored in cooler in working area

23
Vaccine Handling
• Protect from UV light
• Keep in dark covered
container

24
Question?
 After mixing a Modified Live Virus vaccine how long
is it good for?
A. 4 hrs
B. 4 days
C. 4 weeks
D. 4 months

25
Vaccine Handling
• Mix only enough vaccine
for 30 minutes of work
– Live vaccines are “dead”
within 4 hours after mixing

26
Vaccine Handling
• Protect vaccine from contamination
– Do not enter bottles with dirty needles
– Capped needle for vaccine removal
– Transfer needles for mixing

27
Vaccine Handling
• What about syringes and needles?
• Protect from heat
• Never use disinfectants on syringes
– Use hot water ONLY
– Then let air dry

• Do not disinfect needle between animals

28
Vaccine Failure
 Incorrect Administration
 Label directions not followed

 Correct Administration
 Poor Vaccine handling
 Wrong vaccine – Clostridial vaccines
 Antigenic differences – BVDV
 Bad timing – Vaccination to protect fetus ½ way thru pregnancy
 Overwhelming exposure – commingled situations
 Animal fails to respond

•
•
•
•

Immunosuppression – Post partum
Genetics
Nutrition
Passive immunity
29
Vaccine Risks

30
Vaccine Risks
 Injection site lesions

7-way clostridial vaccine given at 50 days of age,
slaughtered at 18 months of age

31
Vaccine Risks
 Injection site lesions
 Type 1 hypersensitivity = Anaphylaxis =
Allergic Reaction

32
Vaccine and Anaphylaxis
 Signs in Cattle
 Immediate to 30 minutes later
 Acute Respiratory Distress
 Muscle tremors
 Salivation
 Go down

 Treatment
 Epinephrine
• 1:1000
– ¼ - ½ cc/100# IV
– 1 cc/100# IM/SQ

33
Vaccine Risks
 Injection site lesions
 Type 1 hypersensitivity (anaphylaxis)
 Endotoxins
 Endotoxins common with gram negative bactrins
 “Endotoxin stacking” – Additive effect from giving multiple gram

negative bactrins
 Results
•
•
•
•

Anaphylaxis
Sick calves
Abortion
Decreased milk production

 Limit number of gram negative bactrins given at one time to 2.
34
Gram Negative Bactrins
•
•
•
•
•
•
•

Salmonella
E. coli
Pasteurella
Mannheimia
Leptospirosis
Moraxella
Histophilus

• Vibrio
• Brucella

35
Vaccine Risks





Injection site lesions
Type 1 hypersensitivity (anaphylaxis)
Endotoxins
Residual virulence
 Attenuated vaccines
• Brucellosis vaccines RB-51
• Shedding

36
Vaccine Risks






Injection site lesions
Type 1 hypersensitivity (anaphylaxis)
Endotoxins
Residual virulence
Human Health Issues
 Brucella abortus
 Johne’s Vaccine

37
Designing a Vaccine Program
What must be considered when deciding what vaccines to
use or recommend?

38
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Veterinary Client Patient Relationship
40
Vaccines

41
Questions and Discussion
Dan Grooms DVM, PhD
groomsd@cvm.msu.edu

42

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Basic Vaccinology: Why Vaccines Work or Don't Work

  • 1. Basic Vaccinology: Why Vaccines Work or Don't Work Dr. Dan Grooms, Michigan State University . 1
  • 2. Objectives Lets think beyond just giving “shots”       What are Vaccines Types of Vaccines Vaccine Failure Vaccine Handling Vaccine Risks Process of Developing a Vaccine Protocol 2
  • 3. What Are Vaccines  Substances that are designed to stimulate an immune response that reduces the risk of a detrimental condition  Substances = antigens  Immune Response = complex response to antigens  Risk Reduction = no vaccines are 100% effective  Detrimental Condition = disease, pathology, death, etc 3
  • 5. Attenuated Vaccines     Also called “modified-live” or “live” vaccines Live replicating organism with reduced virulence Virus or Bacteria Have been manipulated to reduce or eliminate their ability to cause disease  In order to work, they must replicate!! 5
  • 6. Attenuated Vaccines  Advantages  Closely simulate natural infection  Stimulate humoral and cell mediated immunity • Important for intracellular organisms such as viruses  Adjuvants not as necessary  Generally cheaper (Valley Vet On-Line 12-09-13) • Pyramid 5 (MLV) 10 ds = $11.99 • Triangle (killed) 10 ds = $15.65 6
  • 7. Attenuated Vaccines  Disadvantages  Potential to cause pathology • Replicating organism can cause mild signs - Brucellosis • Intact virulence - BVDV, IBR • Potential for reversion to virulence – low, low risk  Contamination • Jencine(4-way live vaccine) contaminated with non-cytopathic BVDV  Stability 7
  • 8. Killed vaccine  Dead organism  Bactrin = Killed bacterial suspension  Key is maintaining antigenic integrity  Usually require adjuvants to adequately stimulate immune system 8
  • 9. Adjuvants  Aid in stimulating immune response to antigen and stabilizing vaccines  Do not confer immunity  Mechanisms  Depot – prolonged exposure • Oil adjuvants  Irritants – amplify response around target antigens • Aluminum hydroxide • Toxins • Adjuvants are not innocuous 9
  • 10. Killed Vaccines  Advantages  Generally safer • No disease due to virulent organism • No contamination  Greater stability  Disadvantages  Hypersensitivity reactions (adjuvants, toxins or large antigen loads)  Endotoxins  More costly • Pyramid 5 (MLV) 10 ds = $11.99 • Triangle (killed) 10 ds = $15.65 10
  • 11. Toxoid  Toxins are the major “virulence” factor of some bacteria which cause disease:  Toxoids contain chemically altered toxins  Stimulate neutralizing antibodies to the toxin  Examples  Clostridium • Tetnus toxoid • C. perfringes C & D toxoid  Mannheimia haemolytica • Leukotoxin  E.coli • Endotoxic mastitis 11
  • 12. Autogenous Vaccines  Made against “farm specific” pathogen  Specific rules regulate their production  Can only be used on the farm that organism was derived from  Generally used when effective commercial vaccine is not available  Example • Mycoplamsa bovis • Clostridium perfringes • Staph aureus 12
  • 14. Vaccine Failure  REMEMEMBER - Vaccines are not 100% effective  They are a tool to use in conjunction with other disease control tools  However, there are things that can reduce efficiency  Incorrect Administration  Correct Administration 14
  • 15. Vaccine Failure  Incorrect Administration  Label directions not followed 15
  • 17. -Dairy DisasterThe case of not reading the label 17
  • 18. Dairy Disaster  150 lactating cow dairy  Acute out break of pneumonia in lactating herd  Necropsy  Severe Acute Emphysematous Bronchopneumonia • Bovine Respiratory Syncytial virus • Mannheimia Pasteurella  45 vows died  Entire herd treated with Ampicillin  Lost milk for ~1 week 18
  • 19. 19
  • 20. Dairy Disaster  Investigation  Recent purchase of new clean-up bull  Herd had been using a modified live viral vaccine that DID NOT contain BRSV.  Admitted, they had not read the label and purchased from catalog because it was less expensive.  Primary BRSV outbreak with secondary Mannheimia haemolytica pneumonia = disaster!! 20
  • 21. Vaccine Failure  Incorrect Administration  Label directions not followed  Correct Administration  Poor Vaccine handling 21
  • 22. Vaccine Handling • Vaccines are biological in nature, therefore very sensitive to the environment. • Damaging the vaccine components reduces the chance of stimulating effective immune response • Improper vaccine handling = Vaccine Failure 22
  • 23. Vaccine Handling • Store refrigerated – 40o F (4 Co) – Not a bad idea to have internal thermometer to monitor fridge temp! • DO NOT FREEZE • Transport in cooler • Stored in cooler in working area 23
  • 24. Vaccine Handling • Protect from UV light • Keep in dark covered container 24
  • 25. Question?  After mixing a Modified Live Virus vaccine how long is it good for? A. 4 hrs B. 4 days C. 4 weeks D. 4 months 25
  • 26. Vaccine Handling • Mix only enough vaccine for 30 minutes of work – Live vaccines are “dead” within 4 hours after mixing 26
  • 27. Vaccine Handling • Protect vaccine from contamination – Do not enter bottles with dirty needles – Capped needle for vaccine removal – Transfer needles for mixing 27
  • 28. Vaccine Handling • What about syringes and needles? • Protect from heat • Never use disinfectants on syringes – Use hot water ONLY – Then let air dry • Do not disinfect needle between animals 28
  • 29. Vaccine Failure  Incorrect Administration  Label directions not followed  Correct Administration  Poor Vaccine handling  Wrong vaccine – Clostridial vaccines  Antigenic differences – BVDV  Bad timing – Vaccination to protect fetus ½ way thru pregnancy  Overwhelming exposure – commingled situations  Animal fails to respond • • • • Immunosuppression – Post partum Genetics Nutrition Passive immunity 29
  • 31. Vaccine Risks  Injection site lesions 7-way clostridial vaccine given at 50 days of age, slaughtered at 18 months of age 31
  • 32. Vaccine Risks  Injection site lesions  Type 1 hypersensitivity = Anaphylaxis = Allergic Reaction 32
  • 33. Vaccine and Anaphylaxis  Signs in Cattle  Immediate to 30 minutes later  Acute Respiratory Distress  Muscle tremors  Salivation  Go down  Treatment  Epinephrine • 1:1000 – ¼ - ½ cc/100# IV – 1 cc/100# IM/SQ 33
  • 34. Vaccine Risks  Injection site lesions  Type 1 hypersensitivity (anaphylaxis)  Endotoxins  Endotoxins common with gram negative bactrins  “Endotoxin stacking” – Additive effect from giving multiple gram negative bactrins  Results • • • • Anaphylaxis Sick calves Abortion Decreased milk production  Limit number of gram negative bactrins given at one time to 2. 34
  • 35. Gram Negative Bactrins • • • • • • • Salmonella E. coli Pasteurella Mannheimia Leptospirosis Moraxella Histophilus • Vibrio • Brucella 35
  • 36. Vaccine Risks     Injection site lesions Type 1 hypersensitivity (anaphylaxis) Endotoxins Residual virulence  Attenuated vaccines • Brucellosis vaccines RB-51 • Shedding 36
  • 37. Vaccine Risks      Injection site lesions Type 1 hypersensitivity (anaphylaxis) Endotoxins Residual virulence Human Health Issues  Brucella abortus  Johne’s Vaccine 37
  • 38. Designing a Vaccine Program What must be considered when deciding what vaccines to use or recommend? 38
  • 39. Ma Ma nagg FFar na a rm em mR em Rssk entt en ii k offD Cap o D Cap abili isse ab l i ea a se itte se i i ie ss e ccne acc iin offV a t V sst o Co Co RisskAcc Ri k A cc epttanc e p a n ce e FarrmGoals Fa m Goals s m em s oblle rrob P mP rrm a rrFFa o aalo n l io n eggio Re R Vacc Va c Vaa Vc cne iine c ci Efffe c in E ec ne ctvve tii e e TT ness ne ss im im ingg in 39
  • 40. Veterinary Client Patient Relationship 40
  • 42. Questions and Discussion Dan Grooms DVM, PhD groomsd@cvm.msu.edu 42