Basic Vaccinology: Why Vaccines Work or Don't Work

Basic Vaccinology:Why Vaccines Work or Don't Work

Dr. Dan Grooms, Michigan State University

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ObjectivesObjectives

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

Lets think beyond just giving “shots”

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What Are VaccinesWhat 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

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Vaccines TypesVaccines Types

AttenuateAttenuatedd

VirulentVirulent

KilleKilledd

RecombinantRecombinantBactrinBactrin

ToxoidsToxoids

Anti-toxinAnti-toxinAutogenouAutogenouss

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Attenuated Vaccines 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!!

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Attenuated VaccinesAttenuated 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

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Attenuated VaccinesAttenuated 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

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Killed vaccineKilled vaccine

Dead organism Bactrin = Killed bacterial suspension

Key is maintaining antigenic integrity Usually require adjuvants to adequately

stimulate immune system

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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

AdjuvantsAdjuvants

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Killed VaccinesKilled 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

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ToxoidToxoid 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

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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

Autogenous VaccinesAutogenous Vaccines

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Vaccine FailureVaccine Failure

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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

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Incorrect Administration Label directions not followed

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Follow the DirectionsFollow the Directions

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-Dairy Disaster-The case of not reading the

label

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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

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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!!

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Correct Administration Poor Vaccine handling

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Vaccine HandlingVaccine 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

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• 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

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• Protect from UV light

• Keep in dark covered container

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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

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• Mix only enough vaccine for 30 minutes of work– Live vaccines are “dead”

within 4 hours after mixing

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• Protect vaccine from contamination– Do not enter bottles with dirty needles

– Capped needle for vaccine removal

– Transfer needles for mixing

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• 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

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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

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Vaccine RisksVaccine Risks

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Injection site lesions


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

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Injection site lesions Type 1 hypersensitivity = Anaphylaxis =

Allergic Reaction


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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

Vaccine and AnaphylaxisVaccine and Anaphylaxis

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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.


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• Salmonella

• E. coli

• Pasteurella

• Mannheimia

• Leptospirosis

• Moraxella

• Histophilus

• Vibrio

• Brucella

Gram Negative BactrinsGram Negative Bactrins

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Injection site lesions Type 1 hypersensitivity (anaphylaxis) Endotoxins Residual virulence

Attenuated vaccines• Brucellosis vaccines RB-51

• Shedding


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Injection site lesions Type 1 hypersensitivity (anaphylaxis) Endotoxins Residual virulence Human Health Issues

Brucella abortus Johne’s Vaccine


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Designing a Vaccine ProgramDesigning a Vaccine Program

What must be considered when deciding what vaccines to use or recommend?

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39Regional or Farm Problems

Regional or Farm Problems

Farm Risk of Disease

Farm Risk of Disease Cost of Vaccine

Cost of Vaccine

Vaccine Effectiveness

Vaccine Effectiveness

Vaccine Timing

Vaccine Timing

Management Capabilities

Management Capabilities

Farm GoalsFarm Goals

Risk AcceptanceRisk Acceptance

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Veterinary Client Patient Relationship

VaccinesVaccines

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Dan Grooms DVM, [email protected]

Questions and DiscussionQuestions and Discussion

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Education

Basic Vaccinology: Why Vaccines Work or Don't Work